Early Production of Type I Interferon during West Nile Virus Infection: Role for Lymphoid Tissues in IRF3-Independent Interferon Production

Abstract

Infection of cells with flaviviruses in vitro is

Interferon Regulatory Factor IRF-7 Induces the Antiviral Alpha Interferon Response and Protects against Lethal West Nile Virus Infection

“…Accordingly, IRF-3 Ϫ/Ϫ mice, similarly to IFN-␣␤R Ϫ/Ϫ mice, show greater WNV burden in the periphery, expanded tissue tropism, and early entry into the CNS, leading to uniform lethality after subcutaneous infection with low doses of virus (6). Somewhat surprisingly, and in contrast to that observed with encephalomyocarditis virus (EMCV) infection (40), an absence of IRF-3 in vivo did not impair the systemic IFN-␣ or IFN-␤ responses after WNV infection (4,6). Ex vivo experiments in primary macrophages showed IRF-3-restricted WNV infection through an IFN-independent mechanism by regulating the basal expression of key host defense molecules, including ISG54, ISG56, RIG-I, and MDA5 (6).…”

“…WNV is a potent trigger of IRF-3 activation (4,14,41,45), and its antiviral response limits the spread of infection. Accordingly, IRF-3 Ϫ/Ϫ mice, similarly to IFN-␣␤R Ϫ/Ϫ mice, show greater WNV burden in the periphery, expanded tissue tropism, and early entry into the CNS, leading to uniform lethality after subcutaneous infection with low doses of virus (6).…”

Identification of Mutated Cyclization Sequences That Permit Efficient Replication of West Nile Virus Genomes: Use in Safer Propagation of a Novel Vaccine Candidate

“…A WNR genome containing the entire WNV C gene (WNR-CNS1-5) was described previously (9). WNR-CNS1-5Rluc was constructed from WNR-CNS1-5 by inserting an IRES (internal ribosome entry site)-driven humanized Renilla luciferase (Rluc) gene into an NsiI site located 39 bases downstream of the termination codon (see Fig.…”

A Single Mutation in the VP1 of Enterovirus 71 Is Responsible for Increased Virulence and Neurotropism in Adult Interferon-Deficient Mice

“…It has also been shown that interferon is one of three major barriers that limit poliovirus trafficking from the periphery to the central nervous system (CNS), and knocking out part of the interferon response allowed a greater portion of the viral population to enter the brain (30). Interferon deficiency of AG129 mice aids in the systemic spread of viral infections (31,32) while maintaining humoral and cell-mediated immunity (33)(34)(35). In our model, eliminating interferon allowed the virus to spread to more organs, including the brain.…”