Format

Send to

Choose Destination
Virus Evol. 2018 Jun 4;4(1):vey012. doi: 10.1093/ve/vey012. eCollection 2018 Jan.

Chikungunya virus evolution following a large 3'UTR deletion results in host-specific molecular changes in protein-coding regions.

Author information

1
Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT 06511-8934, USA.
2
Department of Microbiology, New York University, New York, NY, USA.
3
Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
4
Viral Populations and Pathogenesis Unit, Institut Pasteur, Paris, France.
5
Program in Microbiology, Yale School of Medicine, New Haven, CT, USA.

Abstract

The 3'untranslated region (UTR) in alphavirus genomes functions in virus replication and plays a role in determining virus host range. However, the molecular evolution of virus UTRs is understudied compared to the evolution of protein-coding regions. Chikungunya virus (CHIKV) has the longest 3'UTR among the alphaviruses (500-700 nt), and 3'UTR length and sequence structure vary substantially among different CHIKV lineages. Previous studies showed that genomic deletions and insertions are key drivers of CHIKV 3'UTR evolution. Inspired by hypothesized deletion events in the evolutionary history of CHIKV, we used experimental evolution to examine CHIKV adaptation in response to a large 3'UTR deletion. We engineered a CHIKV mutant with a 258 nt deletion in the 3'UTR (ΔDR1/2). This deletion reduced viral replication on mosquito cells, but did not reduce replication on mammalian cells. To examine how selective pressures from vertebrate and invertebrate hosts shape CHIKV evolution after a deletion in the 3'UTR, we passaged ΔDR1/2 virus populations strictly on primate cells, strictly on mosquito cells, or with alternating primate/mosquito cell passages. We found that virus populations passaged on a single host cell line increased in fitness relative to the ancestral deletion mutant on their selected host, and viruses that were alternately passaged improved on both hosts. Surprisingly, whole genome sequencing revealed few changes in the 3'UTR of passaged populations. Rather, virus populations evolved improved fitness through mutations in protein coding regions that were associated with specific hosts.

KEYWORDS:

adaptation; alphavirus; arbovirus; emerging pathogen; experimental evolution

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center