Analysis of intrahost variation in Venezuelan equine encephalitis virus reveals repeated deletions in the 6-kilodalton protein gene

N. L. Forrester, M. Guerbois, A. P. Adams, X. Liang, Scott Weaver

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

RNA viruses exist as a spectrum of mutants that is generated and maintained during replication within the host. Consensus sequencing overlooks minority genotypes present in the viral sample that may impact the population's phenotype. In-depth sequencing of an original field isolate of subtype IE Venezuelan equine encephalitis virus (VEEV) demonstrated the presence of multiple deletions within the 6,000-molecular-weight (6K) protein gene. Using in vitro and in vivo experiments, similar deletions were generated in an additional VEEV strain originating from an infectious cDNA clone. Time course experiments demonstrated that the deletions are produced during acute infection although not until 24 h postinfection. Molecular clones containing some of these deletions were generated, and although the larger deletions appear to be noninfectious, viruses with the smaller deletions were viable and formed small plaques. Serial passages provided no evidence that these deletion mutants function as defective interfering particles. Furthermore, since wild-type infections generally occur at a low multiplicity of infection, it is unlikely that these deletions are propagated in natural transmission cycles. However, they could affect pathogenesis at later stages of infection. Because they are ubiquitously generated both in vivo and in vitro, further investigation is warranted to understand the generation of these deletions and their significance for disease.

Original languageEnglish (US)
Pages (from-to)8709-8717
Number of pages9
JournalJournal of Virology
Volume85
Issue number17
DOIs
StatePublished - Sep 2011

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Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Infection
infection
Proteins
genes
proteins
Clone Cells
clones
Serial Passage
Defective Viruses
mutants
RNA Viruses
pathogenesis
Complementary DNA
Molecular Weight
Genotype
molecular weight
Viruses
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Virology

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Analysis of intrahost variation in Venezuelan equine encephalitis virus reveals repeated deletions in the 6-kilodalton protein gene. / Forrester, N. L.; Guerbois, M.; Adams, A. P.; Liang, X.; Weaver, Scott.

In: Journal of Virology, Vol. 85, No. 17, 09.2011, p. 8709-8717.

Research output: Contribution to journalArticle

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