title: Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.
abstract: The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments.
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Jianying
authors: J
authors: Liu
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.|SZCDC-SUSTech Joint Key Laboratory for Tropical Diseases, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, China.|School of Life Science, Tsinghua University, Beijing 100084, China.
authors: Yang
authors: Y
authors: Liu
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Kaixiao
authors: K
authors: Nie
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Senyan
authors: S
authors: Du
authors: Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, Shaanxi 710032, China.
authors: Jingjun
authors: J
authors: Qiu
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Xiaojing
authors: X
authors: Pang
authors: Department of Microbiology and Immunology, School of Medicine, New York Medical College, Valhalla, New York 10595, USA.
authors: Penghua
authors: P
authors: Wang
authors: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.|SZCDC-SUSTech Joint Key Laboratory for Tropical Diseases, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, China.
authors: Gong
authors: G
authors: Cheng
mesh_terms: D000818:Animals; D002460:Cell Line; D009033:Culicidae / Q000276:immunology / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics*; D004330:Drosophila; D004664:Encephalitis Virus, Japanese / Q000235:genetics*; D005260:Female; D005416:Flavivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018177:Flavivirus Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017471:Receptors, Interferon / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D017361:Viral Nonstructural Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D014771:Virion
chemical_list: C100315:NS1 protein, Flavivirus; D017471:Receptors, Interferon; D017361:Viral Nonstructural Proteins