High-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections.

J Virol
Authors
Keywords
Abstract

Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia.

Year of Publication
2012
Journal
J Virol
Volume
86
Issue
2
Pages
835-43
Date Published
2012 Jan
ISSN
1098-5514
URL
DOI
10.1128/JVI.05985-11
PubMed ID
22090119
PubMed Central ID
PMC3255838
Links
Grant list
HHSN272200900006C / AI / NIAID NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States