西尼罗河病毒病的研究进展

西尼罗河病毒病是由西尼罗河病毒(West Nile Virus,WNV)引起的一种人畜共患传染病,病原是一种虫媒病毒,可导致西尼罗河热和致死性的西尼罗河脑炎。自发现以来,西尼罗河病毒病曾在世界上多个国家暴发,给畜牧业和人类生命安全造成了巨大的危害。我国目前尚无该病的发生,但是防治技术储备是必要的。本文对西尼罗河病毒病的流行病学、病原学、致病机制、临床症状和病理剖检变化、诊断方法和候选疗法进行综述,为西尼罗河病毒病的防控提供资料。

西尼罗河病肆虐美国

西尼罗河病是由西尼罗河病毒(West Nile Virus,WNV)引起的一种人畜共患的自然疫源性的虫媒传染病,在临床上可表现为症状轻微的流感样的西尼罗河热和症状严重、可导致死亡的西尼罗河脑炎(包括脑膜炎和脑膜脑炎).该病于60年前首次爆发于乌干达,随后传播到非洲各国、欧亚大陆和中东国家,但1999年以前,西半球却从未发现.然而,自1999年8月首次爆发于美国纽约后,该病已迅速肆虐美国.目前已扩展到39个州和地区,仅2002年1-10月,发病人数就已达到3 296例,死亡182人;发病马匹¨526例.而死亡野鸟更多.近期从WHO和OIE网络获悉:加拿大于2001年8月首次从喔太华的一只死亡乌鸦中分离到WNV,近期却传来了有加拿大人死于西尼罗河脑炎的报道.由此可见,该病对人类和动物的健康已构成较大威胁,随着物流的快速发展,人们交流来往的增多,该病正在以令人难以致信的速度传播.因此,我们要予以重视,防患于未然.现对该病及其在美国的流行情况和美国政府为此所采取的措施等进行简要介绍,希望能引起同行们的注意.

西尼罗河病毒和西尼罗河病毒性脑炎

西尼罗河病毒(West Nile virus，WNV)于1937年最先在乌干达的西尼罗河地区发现，当时所引发的传染性疾病称为西尼罗河热(West Nile fever)，在临床表现上类似于登革热的一类疾病，在1999年以前这种虫媒病毒只在东半球发现过，主要分布在非洲和中东地区。

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

Mutagenesis of D80-82 and G83 Residues in West Nile Virus NS2B: Effects on NS2B-NS3 Activity and Viral Replication

Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis substrates. The residues D80DDG in West Nile virus (WNV) NS2B are important for protease activity. To investigate the effects of D80DDG in NS2B on protease activity and viral replication, the negatively charged region D80DD and the conserved residue G83 of NS2B were mutated (D80DD/E80EE, D80DD/K80KK, D80DD/A80AA, G83F, G83S, G83D, G83K, and G83A), and NS3 D75A was designated as the negative control. The effects of the mutations on NS2B-NS3 activity, viral translation, and viral RNA replication were analyzed using kinetic analysis of site-directed enzymes and a transient replicon assay. All substitutions resulted in significantly decreased enzyme activity and blocked RNA replication. The negative charge of D80DD is not important for maintaining NS2B function, but side chain changes in G83 have dramatic effects on protease activity and RNA replication. These results demonstrate that NS2B is important for viral replication and that D80DD and G83 substitutions prevent replication; they will be useful for understanding the relationship between NS2B and NS3.

Development and Characterization of West Nile Virus Replicon Expressing Secreted Gaussia Luciferase

We developed a Gaussia luciferase (Gluc) reporter replicon of West Nile virus (WNV) and used it to quantify viral translation and RNA replication. The advantage of the Gluc replicon is that Gaussia luciferase is secreted into the culture medium from cells transfected with Gluc replicon RNA, and the medium can be assayed directly for luciferase activity. Using a known Flavivirus inhibitor (NITD008), we demonstrated that the Gluc-WNV replicon could be used for antiviral screening. The Gluc-WNV-Rep will be useful for research in antiviral drug development programs, as well as for studying viral replication and pathogenesis of WNV.

Duck egg drop syndrome virus:an emerging Tembusu-related flavivirus in China

Duck egg drop syndrome virus(DEDSV) is a newly emerging pathogenic flavivirus isolated from ducks in China.DEDSV infection mainly results in severe egg drop syndrome in domestic poultry,which leads to huge economic losses.Thus,the discovery of ways and means to combat DEDSV is urgent.Since 2010,a remarkable amount of progress concerning DEDSV research has been achieved.Here,we review current knowledge on the epidemiology,symptomatology,and pathology of DEDSV.A detailed dissection of the viral genome and polyprotein sequences,comparative analysis of viral antigenicity and the corresponding potential immunity against the virus are also summarized.Current findings indicate that DEDSV should be a distinct species from Tembusu virus.Moreover,the adaption of DEDSV in wildlife and its high homology to pathogenic flaviviruses(e.g.,West Nile virus,Japanese encephalitis virus,and dengue virus),illustrate its reemergence and potential to become a zoonotic pathogen that should not be overlooked.Detailed insight into the antigenicity and corresponding immunity against the virus is of clear significance for the development of vaccines and antiviral drugs specific for DEDSV.

Spreading and vanishing in a West Nile virus model with expanding fronts

We study a simplified version of a West Nile virus （WNv） model discussed by Lewis et al. （2006）, which was considered as a first approximation for the spatial spread of WNv. The basic reproduction number R0 for the non-spatial epidemic model is defined and a threshold parameter RD for the corresponding problem with null Dirichlet boundary condition is introduced. We consider a free boundary problem with a coupled system, which describes the diffusion of birds by a PDE and the movement of mosquitoes by an ODE. The risk index R0^F（t） associated with the disease in spatial setting is represented. Sufficient conditions for the WNv to eradicate or to spread are given. The asymptotic behavior of the solution to the system when the spreading occurs is considered. It is shown that the initial number of infected populations, the diffusion rate of birds and the length of initial habitat exhibit important impacts on the vanishing or spreading of the virus. Numerical simulations are presented to illustrate the analytical results.

Origin, dissemination and entry of the pandemic Zika viruses

Zika virus （ZIKV） is a previously-neglected, but newly-emerging zoonotic pathogen that has swept most of the western hemisphere. The unexpected attention aroused worldwide lies in the explosive spread of ZIKV to Brazil and USA in 2015 and its rare correlation to micro- cephaly in newborns, raising a serious challenge to public health. We show the origin and fast dissemination of these epidemic ZIKA isolates. Phylogenetic analyses revealed that all the newly-emerging ZIKV isolates belong to the Asian-American Lineage. Structural analyses of the ZIKV E surface protein suggested that it might adopt a similar entry mechanism to that of other Flavi-viruses like Dengue Virus and West Nile Virus.