Replication Cycle and Molecular Biology of the West Nile Virus

Abstract

West Nile virus (WNV) is a member of the genus Flavivirus in the family Flaviviridae. Flaviviruses replicate in the cytoplasm of infected cells and modify the host cell environment. Although much has been learned about virion structure and virion-endosomal membrane fusion, the cell receptor(s) used have not been definitively identified and little is known about the early stages of the virus replication cycle. Members of the genus Flavivirus differ from members of the two other genera of the family by the lack of a genomic internal ribosomal entry sequence and the creation of invaginations in the ER membrane rather than double-membrane vesicles that are used as the sites of exponential genome synthesis. The WNV genome 3' and 5' sequences that form the long distance RNA-RNA interaction required for minus strand initiation have been identified and contact sites on the 5' RNA stem loop for NS5 have been mapped. Structures obtained for many of the viral proteins have provided information relevant to their functions. Viral nonstructural protein interactions are complex and some may occur only in infected cells. Although interactions between many cellular proteins and virus components have been identified, the functions of most of these interactions have not been delineated.

Next-generation sequencing shows West Nile virus quasispecies diversification after a single passage in a carrion crow (Corvus corone) in vivo infection model

“…Although the primers used for WNV genome amplification did not allow for the complete sequence of the non-coding region (NCR), two mutations emerged in the 39-NCR isolated from some avian samples: locus 10312 in chicken 3 and crows 4 and 6 and locus 10425 in crow 3, whereas no viral subpopulations could be detected in the 59-NCR of our samples. The conservation of the 59-NCR length (constant 96 nt) compared with the 39-NCR (337 to 649 nt depending on strains) was previously demonstrated (Brinton, 2014). On the other hand, the 39-and 59-NCRs fold into RNA secondary structures whose deletion is lethal for WNV infectious clones (Anthony et al, 2009;Brinton & Dispoto, 1988;Brinton et al, 1986;Deas et al, 2005Deas et al, , 2007Elghonemy et al, 2005;Li et al, 2010;Yu & Markoff, 2005).…”

The Composition of West Nile Virus Lipid Envelope Unveils a Role of Sphingolipid Metabolism in Flavivirus Biogenesis

“…The virus is maintained in nature in an enzootic infectious cycle between birds and mosquitoes, which act as its vectors, although it can also infect multiple vertebrate hosts, including horses and humans (1,2). The continuing spread of WNV due to a variety of ecological factors, combined with the lack of specific therapeutics or vaccines for human use, makes the identification of the viral and host processes that control the biology of this pathogen important to improve the design of specific antiviral strategies (3).…”

Transmembrane Domains of NS2B Contribute to both Viral RNA Replication and Particle Formation in Japanese Encephalitis Virus

“…The single open reading frame encodes a long polyprotein that is co-and posttranslationally processed by cellular proteases and viral protease into three structural proteins (capsid [C], premembrane/membrane [prM/ M], and envelope [E]) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (1). The structural proteins form the virus particle, while the nonstructural proteins function in viral RNA replication, virion assembly, and evasion of the host antiviral immune responses (2)(3)(4)(5). Among them, NS3 is a multifunctional protein with an N-terminal protease domain and a C-terminal RNA helicase/NTPase domain.…”