Viral infections play a crucial role in marine biogeochemical cycles,by regulating bacterial mortality and mediating nutrient and carbon fluxes.However,despite of their ecological significance,existing climate change ...Viral infections play a crucial role in marine biogeochemical cycles,by regulating bacterial mortality and mediating nutrient and carbon fluxes.However,despite of their ecological significance,existing climate change models generally fail to incorporate virus-mediated ecological processes due to the current limited understanding of marine viral dynamics under global warming.While numerous studies have explored the effect of warming for viral decay and production,how temperature regulates the total abundance of marine viruses remains unclear.In this study,we conducted year-round measurements of viral production and decay rates in Qingdao's coastal waters,with additional experimental warming treatments.The result showed that under in-situ temperature,the viral decay and production rate displayed distinct seasonal variations.With the exception of summer,elevated temperature stimulated both viral decay rate and production rate,and further improved the net viral production rate.While in summer,the net viral production rate turned negative,implying divergent threshold viral decay and viral production rate on warming.Our study deepens the understanding of the effect of global warming on marine viruses and provides scientific data for climate change models.展开更多
To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor ...To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor expression in ocular tissues,and associated clinical manifestations.This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular,histological,or clinical evidence.The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2(ACE2),including transmembrane serine protease 2(TMPRSS2),CD147,alanyl aminopeptidase N(ANPEP),dipeptidyl peptidase 4(DPP4),angiotensin II receptor type 2(AGTR2),and polymeric immunoglobulin receptor(PIGR),which are expressed in retinal,conjunctival,corneal,limbal,and photoreceptor cells.The virus may also reach ocular structures via neurovascular invasion.Clinically,patients with coronavirus disease 2019(COVID-19)may present with a broad spectrum of ophthalmic manifestations,including conjunctivitis,hyperreflective lesions in the inner retinal layers,flame-shaped hemorrhages,cottonwool spots,retinal pallor,hard exudates,and various forms of maculopathy,such as paracentral acute middle maculopathy and acute macular neuroretinopathy(AMN).These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury.Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis,appropriate ophthalmologic care,and the prevention of long-term visual sequelae in patients affected by COVID-19.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Background:Hua-Yi-Jie-Du formula(HYJD)is a traditional Chinese medicine that has proven effective against viral pneumonia and was extensively used during the COVID-19 pandemic.This study investigates how HYJD influenc...Background:Hua-Yi-Jie-Du formula(HYJD)is a traditional Chinese medicine that has proven effective against viral pneumonia and was extensively used during the COVID-19 pandemic.This study investigates how HYJD influences group 2 innate lymphoid cell(ILC2)and nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation in a mouse model of viral pneumonia.Methods:A mouse model of viral pneumonia was established through the administration of polyinosinic-polycytidylic acid(poly(I:C))via nasal drops.Histopathological analysis of lung tissue was conducted,alongside enzyme-linked immunosorbent assay to quantify cytokine levels in serum and bronchoalveolar lavage fluid(BALF).Flow cytometry was employed to detect ILC2 cells in lung tissue and spleen,while immunofluorescence techniques were utilized to visualize ILC2 cells in lung tissue.Transcriptomic sequencing was performed,and the results were validated using qRT-PCR and western blot analysis.Results:HYJD significantly ameliorated inflammatory infiltration in lung tissue,decreased mucus protein secretion,and reduced the serum levels of inflammatory cytokines interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α).Additionally,it lowered the expression of cytokines IL-4,IL-5,IL-13,IL-25,thymic stromal lymphopoietin(TSLP),and IL-33 in BALF,and reduced the differentiation of ILC2 cells in both lung tissue and spleen.Transcriptomic analysis and experimental validation revealed that HYJD downregulated the expression of NLRP3 related genes and proteins within the NOD-like receptor signaling pathway.Conclusion:The mechanism by which HYJD intervenes in acute lung injury associated with viral pneumonia may involve the reduction of ILC2 cells differentiation and the inhibition of NLRP3 activation.展开更多
Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including no...Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.展开更多
Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virolog...Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virology.An emerging theme is that symptom expressions—such as stunting,curling,and yellowing,which devastate yield—may themselves be evolved viral adaptation strategies rather than collateral damage.展开更多
As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding N...As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding NK cell regulation is of considerable clinical importance.This article reviews the role of circadian processes(melatonin and the cortisol system),aryl hydrocarbon receptor,and vagal nerve in the modulation of NK cell function,highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells.As circadian and exogenous melatonin increase NK cell cytotoxicity,the presence of the endogenous melatonergic pathway may be of some importance not only to NK function and immune checkpoint regulation but also from the efflux of melatonin,which decreases tumor cell survival,proliferation,and metastasis,as well as decreasing immune checkpoint ligands,such as programmed cell ligand 1(PD-L1).NK cell melatonergic pathway regulation may therefore have significant impacts not only on NK cell cytotoxicity but also on the intercellular interactions within tumors and other pathological microenvironments.As melatonin has anti-viral effects,the regulation of the NK cell melatonergic pathway can have wider impacts on how NK cells regulate viral infections,including in the course of viral-induced susceptibility to neurodegenerative conditions.Recent data indicate that the endogenous melatonergic pathway is regulated by interactions of signal transducer and activator of transcription(STAT)3 and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)dimer composition.As both STAT3 and NF-κB dimer composition modulate NK cells,their interaction in the modulation of the NK cell melatonergic pathway will be important to determine.This has significant future research and treatment implications,including improving the clinical efficacy of current treatment approaches such as immune checkpoint inhibition and chimeric antigen receptor(CAR)NK cell therapy,and may accelerate a means of preventing cancer.展开更多
Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges pos...Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.展开更多
Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegment...Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.展开更多
BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and afte...BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.展开更多
The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough establ...The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by dir...Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.展开更多
Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical c...Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.展开更多
BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients followi...BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.展开更多
Viral infections of the ocular surface significantly contribute to morbidity and visual impairment globally.The herpes simplex virus(HSV),adenovirus,cytomegalovirus(CMV),and human papillomavirus(HPV)are predominant pa...Viral infections of the ocular surface significantly contribute to morbidity and visual impairment globally.The herpes simplex virus(HSV),adenovirus,cytomegalovirus(CMV),and human papillomavirus(HPV)are predominant pathogens impacting the cornea and conjunctiva,resulting in recurrent illness,epidemic outbreaks,and virus-associated neoplasia.Progress in virology,immunology,and molecular diagnostics has enhanced comprehension of host–virus interactions and introduced novel therapeutic opportunities.A narrative literature review was performed utilizing PubMed,Scopus,and Web of Science,encompassing papers published from 2000 to 2025,with a specific focus on research from 2020 onwards.Eligible publications were peer-reviewed clinical and experimental investigations,together with reviews that focused on epidemiology,etiology,diagnostic methodologies,and therapeutic alternatives.Research indicates that HSV keratitis is the predominant infectious cause of corneal blindness in high-income nations,although adenovirus persists in instigating epidemics of keratoconjunctivitis in the absence of licensed antiviral treatments.CMV keratitis,previously confined to immunocompromised persons,is now acknowledged in immunocompetent patients as a causative agent of corneal endotheliitis.HPV is associated with ocular surface squamous neoplasia,especially in areas with elevated ultraviolet exposure and high human immunodeficiency virus prevalence.Innovative molecular diagnostics,innovative antiviral agents,immunomodulatory approaches,and immunization initiatives signify significant progress that could enhance preventative and therapeutic results.展开更多
Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and ...Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and therapeutic development due to safety concerns.In this study,we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV.Single-cycle viral replicon particles(VRPs)could be efficiently packaged through trans-complementation of glycoproteins from different strains,recapitulating authentic viral entry and replication while minimizing biosafety risks.Using this system,we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses.Mechanistic studies revealed that CNX-1351 inhibits viral replication,potentially by targeting the PI3K-Akt signaling pathway.This single-cycle VRP system provides a valuable tool for studying RVFV biology,host interactions,antiviral and vaccine development under reduced biosafety constraints.展开更多
Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent ...Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.展开更多
Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning fr...Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
基金supported by the National Natural Science Foundation of China(No.42276108)the Young Scientists Fund of Shandong Provincial Natural Science Foundation(No.ZR2022QD052)。
文摘Viral infections play a crucial role in marine biogeochemical cycles,by regulating bacterial mortality and mediating nutrient and carbon fluxes.However,despite of their ecological significance,existing climate change models generally fail to incorporate virus-mediated ecological processes due to the current limited understanding of marine viral dynamics under global warming.While numerous studies have explored the effect of warming for viral decay and production,how temperature regulates the total abundance of marine viruses remains unclear.In this study,we conducted year-round measurements of viral production and decay rates in Qingdao's coastal waters,with additional experimental warming treatments.The result showed that under in-situ temperature,the viral decay and production rate displayed distinct seasonal variations.With the exception of summer,elevated temperature stimulated both viral decay rate and production rate,and further improved the net viral production rate.While in summer,the net viral production rate turned negative,implying divergent threshold viral decay and viral production rate on warming.Our study deepens the understanding of the effect of global warming on marine viruses and provides scientific data for climate change models.
文摘To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor expression in ocular tissues,and associated clinical manifestations.This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular,histological,or clinical evidence.The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2(ACE2),including transmembrane serine protease 2(TMPRSS2),CD147,alanyl aminopeptidase N(ANPEP),dipeptidyl peptidase 4(DPP4),angiotensin II receptor type 2(AGTR2),and polymeric immunoglobulin receptor(PIGR),which are expressed in retinal,conjunctival,corneal,limbal,and photoreceptor cells.The virus may also reach ocular structures via neurovascular invasion.Clinically,patients with coronavirus disease 2019(COVID-19)may present with a broad spectrum of ophthalmic manifestations,including conjunctivitis,hyperreflective lesions in the inner retinal layers,flame-shaped hemorrhages,cottonwool spots,retinal pallor,hard exudates,and various forms of maculopathy,such as paracentral acute middle maculopathy and acute macular neuroretinopathy(AMN).These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury.Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis,appropriate ophthalmologic care,and the prevention of long-term visual sequelae in patients affected by COVID-19.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
基金supported by Yunnan Provincial Major Science and Technology Special Program(No.202402AA310035)Yunnan Key Laboratory of Dai and Yi Medicines(Yunnan University of Chinese Medicine)(No.2024JS2404)Research Foundation of Chuxiong Medical College(No.2024YYXM38).
文摘Background:Hua-Yi-Jie-Du formula(HYJD)is a traditional Chinese medicine that has proven effective against viral pneumonia and was extensively used during the COVID-19 pandemic.This study investigates how HYJD influences group 2 innate lymphoid cell(ILC2)and nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation in a mouse model of viral pneumonia.Methods:A mouse model of viral pneumonia was established through the administration of polyinosinic-polycytidylic acid(poly(I:C))via nasal drops.Histopathological analysis of lung tissue was conducted,alongside enzyme-linked immunosorbent assay to quantify cytokine levels in serum and bronchoalveolar lavage fluid(BALF).Flow cytometry was employed to detect ILC2 cells in lung tissue and spleen,while immunofluorescence techniques were utilized to visualize ILC2 cells in lung tissue.Transcriptomic sequencing was performed,and the results were validated using qRT-PCR and western blot analysis.Results:HYJD significantly ameliorated inflammatory infiltration in lung tissue,decreased mucus protein secretion,and reduced the serum levels of inflammatory cytokines interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α).Additionally,it lowered the expression of cytokines IL-4,IL-5,IL-13,IL-25,thymic stromal lymphopoietin(TSLP),and IL-33 in BALF,and reduced the differentiation of ILC2 cells in both lung tissue and spleen.Transcriptomic analysis and experimental validation revealed that HYJD downregulated the expression of NLRP3 related genes and proteins within the NOD-like receptor signaling pathway.Conclusion:The mechanism by which HYJD intervenes in acute lung injury associated with viral pneumonia may involve the reduction of ILC2 cells differentiation and the inhibition of NLRP3 activation.
文摘Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.
基金supported by the National Natural Science Foundation of China(32272482)the Innovation Research 2035 Pilot Plan of Southwest University(SWU-XDZD22002).
文摘Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virology.An emerging theme is that symptom expressions—such as stunting,curling,and yellowing,which devastate yield—may themselves be evolved viral adaptation strategies rather than collateral damage.
文摘As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding NK cell regulation is of considerable clinical importance.This article reviews the role of circadian processes(melatonin and the cortisol system),aryl hydrocarbon receptor,and vagal nerve in the modulation of NK cell function,highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells.As circadian and exogenous melatonin increase NK cell cytotoxicity,the presence of the endogenous melatonergic pathway may be of some importance not only to NK function and immune checkpoint regulation but also from the efflux of melatonin,which decreases tumor cell survival,proliferation,and metastasis,as well as decreasing immune checkpoint ligands,such as programmed cell ligand 1(PD-L1).NK cell melatonergic pathway regulation may therefore have significant impacts not only on NK cell cytotoxicity but also on the intercellular interactions within tumors and other pathological microenvironments.As melatonin has anti-viral effects,the regulation of the NK cell melatonergic pathway can have wider impacts on how NK cells regulate viral infections,including in the course of viral-induced susceptibility to neurodegenerative conditions.Recent data indicate that the endogenous melatonergic pathway is regulated by interactions of signal transducer and activator of transcription(STAT)3 and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)dimer composition.As both STAT3 and NF-κB dimer composition modulate NK cells,their interaction in the modulation of the NK cell melatonergic pathway will be important to determine.This has significant future research and treatment implications,including improving the clinical efficacy of current treatment approaches such as immune checkpoint inhibition and chimeric antigen receptor(CAR)NK cell therapy,and may accelerate a means of preventing cancer.
文摘Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.
基金supported by the National Key Research and Development Program of China(2022YFC2303300,2023YFC2605504)the National Natural Science Foundation of China(82172273 and 31670165)the Open Research Fund Program of the State Key Laboratory of Virology of China(2023JZZD-01).
文摘Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.
文摘BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.
文摘The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
基金supported by funding from the National Natural Science Foundation of China(U23A20243 and 32272972 to QZ,32172820 to SX)the Major Science and Technology Project of Gansu Province(22ZD6NA001 to SX)+1 种基金the Youth Innovation Program(Y2023QC30)the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-JBGS-20210102 to SX)of the Chinese Academy of Agricultural Sciences.
文摘Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.
文摘Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.
文摘BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.
文摘Viral infections of the ocular surface significantly contribute to morbidity and visual impairment globally.The herpes simplex virus(HSV),adenovirus,cytomegalovirus(CMV),and human papillomavirus(HPV)are predominant pathogens impacting the cornea and conjunctiva,resulting in recurrent illness,epidemic outbreaks,and virus-associated neoplasia.Progress in virology,immunology,and molecular diagnostics has enhanced comprehension of host–virus interactions and introduced novel therapeutic opportunities.A narrative literature review was performed utilizing PubMed,Scopus,and Web of Science,encompassing papers published from 2000 to 2025,with a specific focus on research from 2020 onwards.Eligible publications were peer-reviewed clinical and experimental investigations,together with reviews that focused on epidemiology,etiology,diagnostic methodologies,and therapeutic alternatives.Research indicates that HSV keratitis is the predominant infectious cause of corneal blindness in high-income nations,although adenovirus persists in instigating epidemics of keratoconjunctivitis in the absence of licensed antiviral treatments.CMV keratitis,previously confined to immunocompromised persons,is now acknowledged in immunocompetent patients as a causative agent of corneal endotheliitis.HPV is associated with ocular surface squamous neoplasia,especially in areas with elevated ultraviolet exposure and high human immunodeficiency virus prevalence.Innovative molecular diagnostics,innovative antiviral agents,immunomodulatory approaches,and immunization initiatives signify significant progress that could enhance preventative and therapeutic results.
基金Grants from the Program of Shanghai Academic Research Leader(22XD1420600)Shanghai Municipal Science and Technology Major Project(ZD2021CY001)+2 种基金National Natural Science Foundation of China(81974305)Shenzhen Medical Research Fund(SMRF No.B2302029)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-02)supported this work.
文摘Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and therapeutic development due to safety concerns.In this study,we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV.Single-cycle viral replicon particles(VRPs)could be efficiently packaged through trans-complementation of glycoproteins from different strains,recapitulating authentic viral entry and replication while minimizing biosafety risks.Using this system,we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses.Mechanistic studies revealed that CNX-1351 inhibits viral replication,potentially by targeting the PI3K-Akt signaling pathway.This single-cycle VRP system provides a valuable tool for studying RVFV biology,host interactions,antiviral and vaccine development under reduced biosafety constraints.
文摘Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.
基金supported by the National Natural Science Foundation of China(32370703)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-1-021,2021-I2M-1-061)the Major Project of Guangzhou National Labora-tory(GZNL2024A01015).
文摘Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
