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Zuo T.,Tsinghua University | Sun J.,Tsinghua University | Sun J.,University of Sichuan | Wang G.,CAS Institut Pasteur of Shanghai | And 16 more authors.
Nature Communications | Year: 2015

Understanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity. Source

Dai L.,Chinese Academy of Sciences | Song J.,CAS Institute of Microbiology | Song J.,University of Chinese Academy of Sciences | Lu X.,CAS Tianjin Institute of Industrial Biotechnology | And 29 more authors.
Cell Host and Microbe | Year: 2016

Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.0 Å and in complex with a flavivirus broadly neutralizing murine antibody 2A10G6 at 3.0 Å. ZIKV-E resembles all the known flavivirus E structures but contains a unique, positively charged patch adjacent to the fusion loop region of the juxtaposed monomer, which may influence host attachment. The ZIKV-E-2A10G6 complex structure reveals antibody recognition of a highly conserved fusion loop. 2A10G6 binds to ZIKV-E with high affinity in vitro and neutralizes currently circulating ZIKV strains in vitro and in mice. The E protein fusion loop epitope represents a potential candidate for therapeutic antibodies against ZIKV. Zika virus (ZIKV) is a mosquito-borne flavivirus. Dai et al. report the structures of ZIKV envelope (E) protein and its complex with a flavivirus broadly protective antibody, which reveals antibody recognition of a conserved fusion loop. Antibody binds to ZIKV-E with high affinity and neutralizes currently circulating ZIKV strains in mice. © 2016 Elsevier Inc. Source

Wang H.,CAS Institute of Microbiology | Wang H.,University of Chinese Academy of Sciences | Shi Y.,CAS Institute of Microbiology | Shi Y.,Chinese Academy of Sciences | And 17 more authors.
Cell | Year: 2016

Filoviruses, including Ebola and Marburg, cause fatal hemorrhagic fever in humans and primates. Understanding how these viruses enter host cells could help to develop effective therapeutics. An endosomal protein, Niemann-Pick C1 (NPC1), has been identified as a necessary entry receptor for this process, and priming of the viral glycoprotein (GP) to a fusion-competent state is a prerequisite for NPC1 binding. Here, we have determined the crystal structure of the primed GP (GPcl) of Ebola virus bound to domain C of NPC1 (NPC1-C) at a resolution of 2.3 Å. NPC1-C utilizes two protruding loops to engage a hydrophobic cavity on head of GPcl. Upon enzymatic cleavage and NPC1-C binding, conformational change in the GPcl further affects the state of the internal fusion loop, triggering membrane fusion. Our data therefore provide structural insights into filovirus entry in the late endosome and the molecular basis for design of therapeutic inhibitors of viral entry. © 2016 Elsevier Inc. Source

Wong G.,CAS Institute of Microbiology | Wong G.,Chinese Academy of SciencesBeijing | Liu W.,CAS Institute of Microbiology | Liu W.,Chinese Academy of SciencesBeijing | And 9 more authors.
Cell Host and Microbe | Year: 2015

Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014-15 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading. © 2015 Elsevier Inc. Source

Su S.,Nanjing Agricultural University | Wong G.,Shenzhen Key Laboratory of Pathogen and Immunity | Wong G.,CAS Institute of Microbiology | Wong G.,Chinese Academy of Sciences | And 16 more authors.
Trends in Microbiology | Year: 2016

Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans. Six coronaviruses (CoVs) are known to infect humans: 229E, OC43, SARS-CoV, NL63, HKU1, and MERS-CoV.Many CoVs are simultaneously maintained in nature, allowing for genetic recombination, resulting in novel viruses.Recombination of CoV in camels has resulted in a dominant MERS lineage that caused human outbreaks in 2015. © 2016 Elsevier Ltd. Source

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