Increased Pathogenicity of West Nile Virus (WNV) by Glycosylation of Envelope Protein and Seroprevalence of WNV in Wild Birds in Far Eastern Russia

Hiroaki Kariwa,Ryo Murata,Kentaro Yoshii,Ikuo Takashima,Masashi Totani

doi:10.3390/ijerph10127144

Abstract

In this review, we discuss the possibility that the glycosylation of West Nile (WN) virus E-protein may be associated with enhanced pathogenicity and higher replication of WN virus. The results indicate that E-protein glycosylation allows the virus to multiply in a heat-stable manner and therefore, has a critical role in enhanced viremic levels and virulence of WN virus in young-chick infection model. The effect of the glycosylation of the E protein on the pathogenicity of WN virus in young chicks was further investigated. The results indicate that glycosylation of the WN virus E protein is important for viral multiplication in peripheral organs and that it is associated with the strong pathogenicity of WN virus in birds. The micro-focus reduction neutralization test (FRNT) in which a large number of serum samples can be handled at once with a small volume (15 μL) of serum was useful for differential diagnosis between Japanese encephalitis and WN virus infections in infected chicks. Serological investigation was performed among wild birds in the Far Eastern region of Russia using the FRNT. Antibodies specific to WN virus were detected in 21 samples of resident and migratory birds out of 145 wild bird samples in the region.

Highlights

The West Nile (WN) virus is a mosquito-borne flavivirus of the Japanese encephalitis (JE)serocomplex group that causes lethal encephalitis in humans and horses
We showed that N-glycosylation of the E protein facilitated efficient multiplication of the NY strain of WN virus at high temperatures in an avian cell culture, and it was responsible for the higher viremic level in an avian host
WN virus causes serious problems in public health since a large numbers of patients with severe encephalitis are reported in various regions of the World

Summary

Introduction

The West Nile (WN) virus is a mosquito-borne flavivirus of the Japanese encephalitis (JE). When an outbreak of WN virus occurred in and around NYC in 1999, many wild and exotic birds died, and encephalitis in humans and horses was reported [15,16]. Injected LP variants resulted in a much higher mortality rate (LD50 < 0.1 PFU) than SP variants (Figure 1), suggesting that glycosylation of the E protein of WN virus is a determinant of pathogenicity in chicks that have been peripherally inoculated. Previous studies showed that avian viremic levels higher than 105 PFU/mL are crucial for the efficient infection of vector Culex tritaeniorhynchus mosquitoes [9] N-linked glycosylation of WN virus E protein is a determinant of high viremic levels in young chicks and suggest that glycosylated WN-virus variants may be more efficiently transmitted to vector mosquitoes than non-glycosylated variants because of higher viremia in infected birds

Increased Replication of Glycosylated WN Virus Variant in Vitro

Replication of WN Virus and Cytokine Responses in Infected Chicks

Seroprevalence of WN Virus in Wild Birds in Far Eastern Russia

Findings

Conclusions