O'nyong nyong Virus Molecular Determinants of Unique Vector Specificity Reside in Non-Structural Protein 3

Kali D Saxton-Shaw,Erin M Borland,Jeffrey Wilusz,Amber J Singh,Ann M Powers,Janae L Stovall,Jeremy P Ledermann,Eric C Mossel,Eva Harris

doi:10.1371/journal.pntd.0001931

Kali D Saxton-Shaw, Erin M Borland + Show 7 more

Open Access

https://doi.org/10.1371/journal.pntd.0001931

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Abstract

O'nyong nyong virus (ONNV) and Chikungunya virus (CHIKV) are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3), was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3) replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.

Highlights

O’nyong nyong virus (ONNV) is an arthropod-borne virus associated with a small number of large- scale epidemics
Previous research using other arboviruses has shown that specific viral genomic regions, amino acid sequences, or even single nucleotide mutations can have a profound effect on virus growth, infection, and virulence characteristics
When ONNV non-structural protein 3 replaced nsP3 from chikungunya virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%

Summary

Introduction

O’nyong nyong virus (ONNV) is an arthropod-borne virus (arbovirus) associated with a small number of large- scale epidemics. One such epidemic began in 1959 in Uganda, lasted three years and affected over 2 million people [1]. The known distribution of ONNV mirrors that of the mosquito vectors that transmit the virus, Anopheles gambiae and Anopheles funestus [5]. Humans are the only currently known reservoir of ONNV [6]. ONNV infection in humans is usually selflimiting, but does cause a low grade-fever, joint pain, lymphadenopathy, and a generalized papular or maculopapular rash [7]

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