Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orth...Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.展开更多
Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thou...Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.展开更多
In recent years,mpox virus Clade Ib has emerged as a significant global public health threat due to its rapid transmission and potential for severe disease outcomes.This strain was first identified in the Democratic R...In recent years,mpox virus Clade Ib has emerged as a significant global public health threat due to its rapid transmission and potential for severe disease outcomes.This strain was first identified in the Democratic Republic of the Congo(DRC)in September 2023 and began spreading to neighboring African countries by July 2024.It was subsequently imported through international travel to 12 non-African countries across Asia,Europe,and the Americas.Clade Ib exhibits increased transmissibility,and current data suggest that infections may lead to more severe symptoms,with higher risks of severe illness and mortality,particularly among vulnerable populations such as children,pregnant individuals,and immunocompromised groups(e.g.,people living with HIV/AIDS).Epidemiologically,Clade Ib primarily spreads through sexual contact,close household contact,and healthcare-related exposure.This review aims to provide an overview of the current understanding of mpox virus Clade Ib,including its genetic characteristics,epidemiological patterns,and prevention and control strategies.Additionally,it discusses the strategies and interventions needed to address this emerging threat.展开更多
In 2022,a global outbreak of mpox was anticipated,with several cases reported in non-endemic countries in early May.Given the challenge of distinguishing the mpox virus(MPXV)from other pathogens based solely on sympto...In 2022,a global outbreak of mpox was anticipated,with several cases reported in non-endemic countries in early May.Given the challenge of distinguishing the mpox virus(MPXV)from other pathogens based solely on symptoms,there is an urgent need for prompt and reliable MPXV detection methods.In this study,we developed assays using recombinase-aided amplification(RAA)to identify MPXV and evaluated their applicability with clinical samples.The assays were designed to detect theN4R gene of MPXV.All assays demonstrated detection limits of 1 copy/μL within the reaction system and exhibited no cross-reactivity with ectromelia or the TianTan strain of vaccinia virus,confirming their high specificity.Our established assay provides results in less than 50 min.Furthermore,we evaluated our assay using clinical samples from laboratory-confirmed mpox patients and demonstrated that the RAA-based assay is valuable for diagnosing MPXV infections in field and clinic settings,especially in areas with limited laboratory resources.Overall,three RAA-based nucleic acid assays for MPXV were established,providing a powerful tool for efficient,rapid,and specific detection of MPXV infection.展开更多
Since May 2022,a severe global Mpox epidemic has underscored the urgent need for a preventative vaccine.On September 16,2022,the mainland of China reported its first case of imported Mpox,which was subsequently follow...Since May 2022,a severe global Mpox epidemic has underscored the urgent need for a preventative vaccine.On September 16,2022,the mainland of China reported its first case of imported Mpox,which was subsequently followed by a significant rise in domestic infections commencing from June 2023.This alarming trend has escalated the likelihood of localized outbreaks and covert transmission,posing a heightened risk to public health.Notably,the United States,many European countries,and Japan have approved the use of smallpox vaccines for Mpox prevention and emergency vaccination post-exposure,based on their cross-protection efficacy.In recent years,virology research has broadened its scope to include investigations into various novel vaccine approaches,such as nucleic acid-based vaccines,protein subunit vaccines,and epitope peptide vaccines,and other related methodologies.This review offers a thorough examination of the current global landscape of Mpox prevalence,delves into the advancements in Mpox vaccine development,and highlights the progress achieved in Mpox vaccine research,serving as a valuable resource and providing technical insights essential for the effective prevention and control of Mpox.展开更多
Mpox(monkeypox)virus(MPXV),which causes a mild smallpox-like disease,has been endemic in Africa for several decades,with sporadic cases occurring in other parts of the world.However,the most recent outbreak of mpox ma...Mpox(monkeypox)virus(MPXV),which causes a mild smallpox-like disease,has been endemic in Africa for several decades,with sporadic cases occurring in other parts of the world.However,the most recent outbreak of mpox mainly among men that have sex with men has affected several continents,posing serious global public health concerns.The infections exhibit a wide spectrum of clinical presentation,ranging from asymptomatic infection to mild,severe disease,especially in immunocompromised individuals,young children,and pregnant women.Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models.However,the continued evolution of MPXV has produced multi-ple lineages,leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines.MPXV infections in various animal models have provided a central plat-form for identification and comparison of diseased pathogenesis between the contemporary and historic isolates.In this review,we discuss the susceptibility of various animals to MPXV,and describe the key pathologic features of rodent,rabbit and nonhuman primate models.We also provide application examples of animal models in elu-cidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs.These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures.Finally,we list some remaining scientific questions of MPXV that can be resolved by animal models.展开更多
Objectives: This research aims to focus on the differences in mpox outbreaks that occurred in 2003 and 2022 in the United States. Methods: We searched the following databases Medline, Google Scholar, Gayle Power Searc...Objectives: This research aims to focus on the differences in mpox outbreaks that occurred in 2003 and 2022 in the United States. Methods: We searched the following databases Medline, Google Scholar, Gayle Power Search, PubMed, and Springerlink using the following search terms “mpox virus”, “MPX”, “mpox in the US”, “US mpox virus 2003”, “US mpox virus 2022”, “US mpox outbreak 2003” and US mpox outbreak 2022”. The only articles selected were those written between 2003 and 2022. Results: Findings showed more Mpox research was conducted during the first US Mpox outbreak in 2003 compared to the US Mpox outbreak in 2022. Findings also indicated that the mpox outbreak of 2003 consisted of more animal-to-human transmissions acquired from sick prairie dogs compared to more human-to-human from an infected international traveler from Nigeria to the US. Conclusion: Major differences in the mpox outbreaks in the US include the number, location of lesions, and transmission type. We recommend further research to increase awareness of the human-to-human transmission of mpox via sexual contact to assist healthcare professionals and public health leaders in providing prevention and wellness in US communities.展开更多
Treatment of mpox virus(MPxV)is crucial for public health.However,research into drugs for MPxV has fallen behind,particularly in anticipation of sudden outbreaks.This study aimed to identify new inhibitors of Orthopox...Treatment of mpox virus(MPxV)is crucial for public health.However,research into drugs for MPxV has fallen behind,particularly in anticipation of sudden outbreaks.This study aimed to identify new inhibitors of Orthopoxvirus using artificial intelligence(Al)-assisted methods.We explored AlphaFold v2.0 to simulate the F13 protein structures of MPXV,vaccinia virus(VACV),and variola virus(VARV).Utilizing MOE2019 software,we identified amino acid binding sites suitable for small molecule docking,focusing on a phosphodiesterase active site pocket in F13.Our efforts led to the identification of JCs-2022,a promising new inhibitor that exhibited docking similarities with the known anti-poxvirus drug tecovirimat.In vitro experiments demonstrated that JCS-2022 had a half maximal effective concentration(ECso)of 0.05430μmol/L(μM),comparable to tecovirimat's ECso of 0.04794μM.At a dosage of 1.6μM,JCS-2022 significantly reduced VACV plaque size,indicating effective inhibition of extracellular enveloped virus(EEV)formation.Immunofluorescence analysis confirmed a reduction in VACV-induced actin tail formation.Our findings suggest that JCS-2022 is a strong candidate for development as a small molecule inhibitor against Orthopoxvirus,highlighting the potential of Al-assisted methods in accelerating drug discovery for infectious diseases.展开更多
The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequ...The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequences and codon usage in MPXV.We first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of MPXV.Subsequently,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak.Furthermore,we showed strong epistasis between amino acid substitutions located in different genes.The codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱb-B.While the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates.This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.展开更多
Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is rec...Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission.However,few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions,and their sensitivity to biocides.Here,we systematically measured the stability of vaccinia virus(VACV)under different environmental conditions and sensitivity to inactivation methods via plaque assay,quantitative real‐time polymerase chain reaction(qPCR),and Gaussia luciferase(G‐luciferase)reporter system.The results show that VACV is stable on the surface of stainless steel,glass,clothing,plastic,towel,A4 paper,and tissue and persists much longer at 4℃ and?20℃,but is effectively inactivated by ultraviolet(UV)irradiation,heat treatment,and chemical reagents.Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants,which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.展开更多
Mpox is a zoonotic infectious disease caused by the mpox virus(MPXV).Historically,the majority of mpox cases have been documented in Central Africa.However,since May 2022,there has been a notable rise in reported case...Mpox is a zoonotic infectious disease caused by the mpox virus(MPXV).Historically,the majority of mpox cases have been documented in Central Africa.However,since May 2022,there has been a notable rise in reported cases from regions beyond Africa.Currently,over 110 countries spanning Europe,North America,South America,Asia,and other territories have reported mpox infections.This report details a case involving a patient who identifies as a man who has sex with men(MSM)and is concurrently infected with MPXV,human immunodeficiency virus type 1(HIV-1),Pneumocystis jiroveci,as well as extensively drug-resistant tuberculosis(XDR-TB).This patient had also received a vaccination for smallpox in the past.Additionally,we provide photographic documentation charting the progression of dermatological manifestations associated with mpox.This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox.The rapid and widespread dissemination of the MPXV across various regions,especially among MSM communities,underscores the importance of enhancing preventive education efforts targeted at high-risk populations.展开更多
In 2022,a sharp rise in global cases of mpox virus(MPXV)led the World Health Organization(WHO)to declare it a public health emergency of international concern.However,progress in developing drugs targeting MPXV has be...In 2022,a sharp rise in global cases of mpox virus(MPXV)led the World Health Organization(WHO)to declare it a public health emergency of international concern.However,progress in developing drugs targeting MPXV has been slow.Here,we investigate the natural alkaloid narciclasine as a potential inhibitor of poxviruses.Our investigation demonstrates that narciclasine at 40 nmol/L(nM)to 160 nM dosages effectively blocks vaccinia virus(VACV),a representative poxvirus.Specifically,narciclasine disrupts the production of extracellular enveloped virus(EEV),which is crucial for viral spread.Narciclasine’s antiviral impact is probably attributed to its activation of the RhoA signaling pathway.This study highlights narciclasine’s potential as a promising new therapeutic candidate against poxviruses,offering prospects for its development into a potent antiviral agent that is essential for combating emerging poxvirus outbreaks.展开更多
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2023-I2M-2-001National Key Research and Development Project of China,Grant/Award Number:2022YFC2304100 and 2023YFC2309000+1 种基金National Natural Science Foundation of China,Grant/Award Number:82241068 and 82222041Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.
基金supported by the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018 to B.S.)Beijing Key Laboratory for HIV/AIDS Research(BZ0089).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.
基金Supported by Research on Genetic Evolution Characteristics and Key Techniques for Tracing of Highly Pathogenic Viruses(2023YFC2605602)the key research project of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(2023-2025)(GWVI-3)+3 种基金Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(2023-2025)Key Discipline Project(GWVI-11.1-12)Key Discipline-Infectious Diseases of Threeyear Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System(2023-2025)(GWVI-11.1-01)the Key Discipline Program on Public Health System Construction of Shanghai(GWVI-11.1-15)Shanghai Municipal Science and Technology Major Project(ZD2021CY001).
文摘In recent years,mpox virus Clade Ib has emerged as a significant global public health threat due to its rapid transmission and potential for severe disease outcomes.This strain was first identified in the Democratic Republic of the Congo(DRC)in September 2023 and began spreading to neighboring African countries by July 2024.It was subsequently imported through international travel to 12 non-African countries across Asia,Europe,and the Americas.Clade Ib exhibits increased transmissibility,and current data suggest that infections may lead to more severe symptoms,with higher risks of severe illness and mortality,particularly among vulnerable populations such as children,pregnant individuals,and immunocompromised groups(e.g.,people living with HIV/AIDS).Epidemiologically,Clade Ib primarily spreads through sexual contact,close household contact,and healthcare-related exposure.This review aims to provide an overview of the current understanding of mpox virus Clade Ib,including its genetic characteristics,epidemiological patterns,and prevention and control strategies.Additionally,it discusses the strategies and interventions needed to address this emerging threat.
基金supported by the Beijing Natural Science Foundation(7254390)the Youth Science Foundation of the Chinese Center for Disease Control and Prevention(2024A103)the National Key R&D Program of China(2022YFC2303400).
文摘In 2022,a global outbreak of mpox was anticipated,with several cases reported in non-endemic countries in early May.Given the challenge of distinguishing the mpox virus(MPXV)from other pathogens based solely on symptoms,there is an urgent need for prompt and reliable MPXV detection methods.In this study,we developed assays using recombinase-aided amplification(RAA)to identify MPXV and evaluated their applicability with clinical samples.The assays were designed to detect theN4R gene of MPXV.All assays demonstrated detection limits of 1 copy/μL within the reaction system and exhibited no cross-reactivity with ectromelia or the TianTan strain of vaccinia virus,confirming their high specificity.Our established assay provides results in less than 50 min.Furthermore,we evaluated our assay using clinical samples from laboratory-confirmed mpox patients and demonstrated that the RAA-based assay is valuable for diagnosing MPXV infections in field and clinic settings,especially in areas with limited laboratory resources.Overall,three RAA-based nucleic acid assays for MPXV were established,providing a powerful tool for efficient,rapid,and specific detection of MPXV infection.
文摘Since May 2022,a severe global Mpox epidemic has underscored the urgent need for a preventative vaccine.On September 16,2022,the mainland of China reported its first case of imported Mpox,which was subsequently followed by a significant rise in domestic infections commencing from June 2023.This alarming trend has escalated the likelihood of localized outbreaks and covert transmission,posing a heightened risk to public health.Notably,the United States,many European countries,and Japan have approved the use of smallpox vaccines for Mpox prevention and emergency vaccination post-exposure,based on their cross-protection efficacy.In recent years,virology research has broadened its scope to include investigations into various novel vaccine approaches,such as nucleic acid-based vaccines,protein subunit vaccines,and epitope peptide vaccines,and other related methodologies.This review offers a thorough examination of the current global landscape of Mpox prevalence,delves into the advancements in Mpox vaccine development,and highlights the progress achieved in Mpox vaccine research,serving as a valuable resource and providing technical insights essential for the effective prevention and control of Mpox.
基金supported by the Pear River Talent Plan in Guangdong Province in China (2019CX01N111)the Medical Innovation Team Project of Jilin University (2022JBGS02).
文摘Mpox(monkeypox)virus(MPXV),which causes a mild smallpox-like disease,has been endemic in Africa for several decades,with sporadic cases occurring in other parts of the world.However,the most recent outbreak of mpox mainly among men that have sex with men has affected several continents,posing serious global public health concerns.The infections exhibit a wide spectrum of clinical presentation,ranging from asymptomatic infection to mild,severe disease,especially in immunocompromised individuals,young children,and pregnant women.Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models.However,the continued evolution of MPXV has produced multi-ple lineages,leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines.MPXV infections in various animal models have provided a central plat-form for identification and comparison of diseased pathogenesis between the contemporary and historic isolates.In this review,we discuss the susceptibility of various animals to MPXV,and describe the key pathologic features of rodent,rabbit and nonhuman primate models.We also provide application examples of animal models in elu-cidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs.These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures.Finally,we list some remaining scientific questions of MPXV that can be resolved by animal models.
文摘Objectives: This research aims to focus on the differences in mpox outbreaks that occurred in 2003 and 2022 in the United States. Methods: We searched the following databases Medline, Google Scholar, Gayle Power Search, PubMed, and Springerlink using the following search terms “mpox virus”, “MPX”, “mpox in the US”, “US mpox virus 2003”, “US mpox virus 2022”, “US mpox outbreak 2003” and US mpox outbreak 2022”. The only articles selected were those written between 2003 and 2022. Results: Findings showed more Mpox research was conducted during the first US Mpox outbreak in 2003 compared to the US Mpox outbreak in 2022. Findings also indicated that the mpox outbreak of 2003 consisted of more animal-to-human transmissions acquired from sick prairie dogs compared to more human-to-human from an infected international traveler from Nigeria to the US. Conclusion: Major differences in the mpox outbreaks in the US include the number, location of lesions, and transmission type. We recommend further research to increase awareness of the human-to-human transmission of mpox via sexual contact to assist healthcare professionals and public health leaders in providing prevention and wellness in US communities.
基金supported by the National Natural Science Foundation of China(82272306 and 82072270)the Taishan Scholars Program(tstp20221142).
文摘Treatment of mpox virus(MPxV)is crucial for public health.However,research into drugs for MPxV has fallen behind,particularly in anticipation of sudden outbreaks.This study aimed to identify new inhibitors of Orthopoxvirus using artificial intelligence(Al)-assisted methods.We explored AlphaFold v2.0 to simulate the F13 protein structures of MPXV,vaccinia virus(VACV),and variola virus(VARV).Utilizing MOE2019 software,we identified amino acid binding sites suitable for small molecule docking,focusing on a phosphodiesterase active site pocket in F13.Our efforts led to the identification of JCs-2022,a promising new inhibitor that exhibited docking similarities with the known anti-poxvirus drug tecovirimat.In vitro experiments demonstrated that JCS-2022 had a half maximal effective concentration(ECso)of 0.05430μmol/L(μM),comparable to tecovirimat's ECso of 0.04794μM.At a dosage of 1.6μM,JCS-2022 significantly reduced VACV plaque size,indicating effective inhibition of extracellular enveloped virus(EEV)formation.Immunofluorescence analysis confirmed a reduction in VACV-induced actin tail formation.Our findings suggest that JCS-2022 is a strong candidate for development as a small molecule inhibitor against Orthopoxvirus,highlighting the potential of Al-assisted methods in accelerating drug discovery for infectious diseases.
基金We thank the researchers who generated and shared the sequencing data in the NCBI(Table S4)and GISAID(https://www.gisaid.org/)(Table S5),on which this research is basedThis work is supported by the National Key R&D Projects of China(Grant Nos.2021YFC2301300,2022YFC2304100,and 2022YFC2303401)+2 种基金the National Natural Science Foundation of China(Grant No.82241080)the Beijing Natural Science Foundation,China(Grant No.L222009)the SLS-Qidong Innovation Fund,China,and the Beijing Postdoctoral Research Foundation,China(Grant No.2023-ZZ-018).
文摘The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequences and codon usage in MPXV.We first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of MPXV.Subsequently,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak.Furthermore,we showed strong epistasis between amino acid substitutions located in different genes.The codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱb-B.While the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates.This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.
基金supported by funds from the National Key R&D Program of China (2022YFE0203100)the CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-038 and CIFMS 2022-I2M-1-021)the National Natural Science Foundation of China (82271802,82241075,and 82072288).
文摘Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission.However,few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions,and their sensitivity to biocides.Here,we systematically measured the stability of vaccinia virus(VACV)under different environmental conditions and sensitivity to inactivation methods via plaque assay,quantitative real‐time polymerase chain reaction(qPCR),and Gaussia luciferase(G‐luciferase)reporter system.The results show that VACV is stable on the surface of stainless steel,glass,clothing,plastic,towel,A4 paper,and tissue and persists much longer at 4℃ and?20℃,but is effectively inactivated by ultraviolet(UV)irradiation,heat treatment,and chemical reagents.Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants,which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.
基金the National Natural Science Foundation of China(Nos.82241068 and 82241072).
文摘Mpox is a zoonotic infectious disease caused by the mpox virus(MPXV).Historically,the majority of mpox cases have been documented in Central Africa.However,since May 2022,there has been a notable rise in reported cases from regions beyond Africa.Currently,over 110 countries spanning Europe,North America,South America,Asia,and other territories have reported mpox infections.This report details a case involving a patient who identifies as a man who has sex with men(MSM)and is concurrently infected with MPXV,human immunodeficiency virus type 1(HIV-1),Pneumocystis jiroveci,as well as extensively drug-resistant tuberculosis(XDR-TB).This patient had also received a vaccination for smallpox in the past.Additionally,we provide photographic documentation charting the progression of dermatological manifestations associated with mpox.This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox.The rapid and widespread dissemination of the MPXV across various regions,especially among MSM communities,underscores the importance of enhancing preventive education efforts targeted at high-risk populations.
基金supported by the National Natural Science Foundation of China(82272306 and 82072270)Shandong Provincial Natural Science Foundation(ZR2024MH017)Taishan Scholars Program(tstp20221142).
文摘In 2022,a sharp rise in global cases of mpox virus(MPXV)led the World Health Organization(WHO)to declare it a public health emergency of international concern.However,progress in developing drugs targeting MPXV has been slow.Here,we investigate the natural alkaloid narciclasine as a potential inhibitor of poxviruses.Our investigation demonstrates that narciclasine at 40 nmol/L(nM)to 160 nM dosages effectively blocks vaccinia virus(VACV),a representative poxvirus.Specifically,narciclasine disrupts the production of extracellular enveloped virus(EEV),which is crucial for viral spread.Narciclasine’s antiviral impact is probably attributed to its activation of the RhoA signaling pathway.This study highlights narciclasine’s potential as a promising new therapeutic candidate against poxviruses,offering prospects for its development into a potent antiviral agent that is essential for combating emerging poxvirus outbreaks.
