An SIR model of Zika virus (ZIKV) spread is formulated that includes ZIKV infections to newborns. Analytically, the model has one disease free and one endemic equilibrium point. The free one is stable for some conditi...An SIR model of Zika virus (ZIKV) spread is formulated that includes ZIKV infections to newborns. Analytically, the model has one disease free and one endemic equilibrium point. The free one is stable for some conditions when R0 and unstable when R0>1. In Brazil, when R0≈2>1 ZIKV infections expand and for R0 = 0.875R0) of the model. There are parameters for human-mosquito transmission and some for sexual-transmission factor. It appears that controlling spread of ZIKV infections by human-mosquito transmission may greatly reduce the value of R0.展开更多
As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)...As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)secretion,growth delay and deficits in learning and memory in suckling mice.Early administration of GH can improve the cognitive function of the mice.Therefore,in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice.Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication.Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.展开更多
Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we ha...Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we have intracranially serially passaged a clinical ZIKV isolate(SW01)in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism.Deep sequencing analysis combining with molecular virology studies revealed that a single 67D(Aspartic acid)to N(Asparagine)substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo.Notably,virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect(CPE)in human neural astrocytes U251 cells in vitro,indicating its potential neurological toxicity to human brain.These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.展开更多
Nowadays the Zika virus (ZIKV) has been one of the most studied vector-borne diseases due to the considerable outbreaks that have generated around the world as well as due to the new transmission mechanisms and health...Nowadays the Zika virus (ZIKV) has been one of the most studied vector-borne diseases due to the considerable outbreaks that have generated around the world as well as due to the new transmission mechanisms and health complications originated. According to statistics of the INS-Colombia for July 2016, 68% of the population infected by ZIKV (confirmed cases) are pregnant women. Furthermore, the Quindío department belongs to the states with more than 50% of the total infected persons being pregnant women. Taking into account those characteristics, a theoretical model is proposed and analyzed to describe the population dynamics considering the sexual and vectorial transmission of ZIKV, with special emphasis in the consequences of the non-vectorial transmission in the population. The obtained results with simulations through the beta parameter indicate that the probability of sexual transmission between susceptible women and infected men points out the importance of campaigns to inculcate prevention measures for the safe sexual relationships between ZIKV infected population.展开更多
Antibodies targeting non-structural protein 1(NS1)confer protection against Zika virus(ZIKV).Although monoclonal an-tibodies(MAbs)3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mic...Antibodies targeting non-structural protein 1(NS1)confer protection against Zika virus(ZIKV).Although monoclonal an-tibodies(MAbs)3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models,the epitopes are unclear.Herein,we determined the Cryo-electron microscopy(Cryo-EM)structures of ZIKV NS1 in com-plex withfive human antibodies at 2.6–2.9Åresolution.Group I antibodies(3G2 and 4B8)recognize the previously un-reported epitopes on the outer surface of the NS1 dimer.The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1(sNS1)-induced endothelial permeability via their immunoglobulin G(IgG)and Fab.Group II antibodies(4F10,2E11,and 14G5)recognize common epitopes in the distal end of the b-ladder domain,with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG.Thesefindings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.展开更多
Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Cu...Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Currently,there is no commercial vaccine or specific treatment available to prevent ZIKV infection.Therefore,controlling the epidemic's spread relies on preventing mosquitoes from transmitting the virus.Although various studies have explored the transmission of ZIKV between mosquitoes and vertebrate hosts,comprehensive research on potential mosquito-to-mosquito transmission of ZIKV remains limited.In this study,we conducted systematic laboratory investigations to assess the ability of ZIKV to spread among mosquitoes,and to evaluate the impact of ZIKV infection on mosquito development.Our findings revealed that ZIKV can be transmitted between Aedes aegypti mosquitoes both vertically and horizontally,through oviposition and contact between mosquitoes of the same or opposite sex.Additionally,we observed that ZIKV infection resulted in a reduction in the number of mosquito eggs but an increase in their size.The widespread distribution of ZIKV in infected mosquitoes and the altered levels of hormone related genes following viral infection were noted,which may contribute to viral transmission among mosquitoes and affect mosquito development.This research provides systematic experimental evidence of ZIKV transmission among mosquitoes,which is crucial for developing novel strategies to disrupt the spread of orthoflaviviruses and other mosquitoborne pathogens.展开更多
In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Boju...In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.展开更多
Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pat...Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pathogens and the host immune system plays a critical role in the pathogenesis and treatment of VRTIs.This review aims to provide a comprehensive overview of the multifaceted roles of the immune system in both contributing to and combating VRTIs.The review will also address the consequent perturbations in immune homeostasis and the implications for disease manifestation and progression.The interrelation between systemic immunity and local immune responses is discussed,providing insights into the challenges and breakthroughs in managing these infections.By providing a comprehensive overview of the mechanisms,implications,and therapeutic strategies associated with viral reproductive tract infections and immune dysfunction,this review also informs future research and clinical practice in this important area of reproductive health.展开更多
The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related stu...The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKVin the process of ZIKVinfection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.展开更多
Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigate...Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.展开更多
文摘An SIR model of Zika virus (ZIKV) spread is formulated that includes ZIKV infections to newborns. Analytically, the model has one disease free and one endemic equilibrium point. The free one is stable for some conditions when R0 and unstable when R0>1. In Brazil, when R0≈2>1 ZIKV infections expand and for R0 = 0.875R0) of the model. There are parameters for human-mosquito transmission and some for sexual-transmission factor. It appears that controlling spread of ZIKV infections by human-mosquito transmission may greatly reduce the value of R0.
基金the grants from the National Key Research and Development Plan of China(2021YFC2300200)the National Natural Science Foundation of China(NSFC)(U1902210 and 81972979 to J.An,and 82172266 to P.G.Wang)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Fiveyear Plan(IDHT20190510 to J.An)。
文摘As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)secretion,growth delay and deficits in learning and memory in suckling mice.Early administration of GH can improve the cognitive function of the mice.Therefore,in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice.Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication.Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.
基金supported in part by the following grants:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040301 to X.J.)National Key R&D Program of China(2016YFC1201000 to X.J.)+2 种基金Ministry of Science and Technology of China(2016YFE0133500 to X.J.)the National Natural Science Foundation of China(31770190 and 81925025 to CF.Q.)European Union Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement(734548 to X.J.)
文摘Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we have intracranially serially passaged a clinical ZIKV isolate(SW01)in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism.Deep sequencing analysis combining with molecular virology studies revealed that a single 67D(Aspartic acid)to N(Asparagine)substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo.Notably,virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect(CPE)in human neural astrocytes U251 cells in vitro,indicating its potential neurological toxicity to human brain.These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.
文摘Nowadays the Zika virus (ZIKV) has been one of the most studied vector-borne diseases due to the considerable outbreaks that have generated around the world as well as due to the new transmission mechanisms and health complications originated. According to statistics of the INS-Colombia for July 2016, 68% of the population infected by ZIKV (confirmed cases) are pregnant women. Furthermore, the Quindío department belongs to the states with more than 50% of the total infected persons being pregnant women. Taking into account those characteristics, a theoretical model is proposed and analyzed to describe the population dynamics considering the sexual and vectorial transmission of ZIKV, with special emphasis in the consequences of the non-vectorial transmission in the population. The obtained results with simulations through the beta parameter indicate that the probability of sexual transmission between susceptible women and infected men points out the importance of campaigns to inculcate prevention measures for the safe sexual relationships between ZIKV infected population.
基金supported by grants from the National Natural Science Foundation of China(81971924 to L.Y.and 32370146 to W.Z.)Guangzhou Municipal Science and Technology Bureau(2023A03J0791 to L.Y.)+6 种基金Guangdong Science and Technology Program(2021B1212030014 to W.Z.)Guangdong Basic and Applied Basic Research Fund Enterprise Joint Fund(2021A1515220017 to W.Z.)Medical Scientific Research Foundation of Guangdong Province(B2022112 to J.Y.),Shenzhen Science and Technology Innovation Committee(JCYJ20210324131802008 to H.H.)Ganghong Young Scholar Development Fund(to H.H.)the Shenzhen-Hong Kong Cooperation Zone for Technology and Innovation(HZQB-KCZYB-2020056 to H.H.)the Kobilka Institute of Innovative Drug Discovery and Presidential Fellowship and University Development Fund at the Chinese University of Hong Kong,Shenzhen(to H.H.,H.J.,and Q.C.)Presidential Fellowship at the Chinese University of Hong Kong,Shenzhen(to Q.P.and W.Z.)。
文摘Antibodies targeting non-structural protein 1(NS1)confer protection against Zika virus(ZIKV).Although monoclonal an-tibodies(MAbs)3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models,the epitopes are unclear.Herein,we determined the Cryo-electron microscopy(Cryo-EM)structures of ZIKV NS1 in com-plex withfive human antibodies at 2.6–2.9Åresolution.Group I antibodies(3G2 and 4B8)recognize the previously un-reported epitopes on the outer surface of the NS1 dimer.The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1(sNS1)-induced endothelial permeability via their immunoglobulin G(IgG)and Fab.Group II antibodies(4F10,2E11,and 14G5)recognize common epitopes in the distal end of the b-ladder domain,with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG.Thesefindings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.
基金supported by National Key Research and Development Program of China,China(2024YFD1800102,2022YFD1800105 and 2022YFD1801500)National Natural Science Foundation of China,China(32372993 and 32030107)Fundamental Research Funds for the Central Universities,China(2662023PY005).
文摘Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Currently,there is no commercial vaccine or specific treatment available to prevent ZIKV infection.Therefore,controlling the epidemic's spread relies on preventing mosquitoes from transmitting the virus.Although various studies have explored the transmission of ZIKV between mosquitoes and vertebrate hosts,comprehensive research on potential mosquito-to-mosquito transmission of ZIKV remains limited.In this study,we conducted systematic laboratory investigations to assess the ability of ZIKV to spread among mosquitoes,and to evaluate the impact of ZIKV infection on mosquito development.Our findings revealed that ZIKV can be transmitted between Aedes aegypti mosquitoes both vertically and horizontally,through oviposition and contact between mosquitoes of the same or opposite sex.Additionally,we observed that ZIKV infection resulted in a reduction in the number of mosquito eggs but an increase in their size.The widespread distribution of ZIKV in infected mosquitoes and the altered levels of hormone related genes following viral infection were noted,which may contribute to viral transmission among mosquitoes and affect mosquito development.This research provides systematic experimental evidence of ZIKV transmission among mosquitoes,which is crucial for developing novel strategies to disrupt the spread of orthoflaviviruses and other mosquitoborne pathogens.
文摘In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.
基金supported by the Universiti Malaya ArtScience Fellowship Grant(UMG004-2024IAS)UM Community Engagement Grant 2023(Project RUU002-23KS).
文摘Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pathogens and the host immune system plays a critical role in the pathogenesis and treatment of VRTIs.This review aims to provide a comprehensive overview of the multifaceted roles of the immune system in both contributing to and combating VRTIs.The review will also address the consequent perturbations in immune homeostasis and the implications for disease manifestation and progression.The interrelation between systemic immunity and local immune responses is discussed,providing insights into the challenges and breakthroughs in managing these infections.By providing a comprehensive overview of the mechanisms,implications,and therapeutic strategies associated with viral reproductive tract infections and immune dysfunction,this review also informs future research and clinical practice in this important area of reproductive health.
文摘The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKVin the process of ZIKVinfection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.
基金supported by the National Key Research and Development Program of China(2022YFD1800100)the National Natural Science Foundation of China(32302843,32070702,and 82161128014)+5 种基金GuangDong Basic and Applied Basic Research Foundation(2023A1515010748)Innovation and Technology Fund of Hong Kong(MRP/064/21,GHP/097/20GD,and MHP/072/21)Hong Kong Research Grant Council(RGC)grant(11103620 and 11104422)research grants from Shenzhen Science and Technology Innovation Committee(SGDX20201103093201010 and JCYJ20210324134007020)Kunshan Shuang Chuang Grant(kssc202302073)the Kunshan Municipal Government research funding。
文摘Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.
