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Retrovirology. 2017 Oct 10;14(1):46. doi: 10.1186/s12977-017-0371-4.

A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies.

Author information

1
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
2
Department of Medicine, Duke Human Vaccine Institute, Duke University Medical Center, 303 Research Dr., 244 Sands Building, DUMC 102359, Durham, NC, 27710, USA.
3
Division II of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, China.
4
Department of Microbiology, Immunology and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
5
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, England, UK.
6
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
7
Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
8
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China. fgao@duke.edu.
9
Department of Medicine, Duke Human Vaccine Institute, Duke University Medical Center, 303 Research Dr., 244 Sands Building, DUMC 102359, Durham, NC, 27710, USA. fgao@duke.edu.

Abstract

BACKGROUND:

Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral fitness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in fitness losses.

RESULTS:

Strongly selected mutations were identified by analyzing 5'-half HIV-1 genome (gag/pol) sequences from longitudinal samples of subject CH0131. The K43R mutation in the gag gene was first detected at day 91 post screening and was fixed in the viral population at day 273 while the synonymous N323tc mutation was first detected at day 177 and fixed at day 670. No conventional or cryptic T cell responses were detected against either mutation sites by ELISpot analysis. However, when fitness costs of both mutations were measured by introducing each mutation into their cognate transmitted/founder (T/F) viral genome, the K43R mutation caused a significant fitness loss while the N323tc mutation had little impact on viral fitness.

CONCLUSIONS:

The rapid fixation, the lack of detectable immune responses and the significant fitness cost of the K43R mutation suggests that it was strongly selected by host factors other than T cell responses and neutralizing antibodies.

KEYWORDS:

Cryptic T cell response; Escape; Fitness; Immune responses; Mutation; Selection

PMID:
29017536
PMCID:
PMC5634943
DOI:
10.1186/s12977-017-0371-4
[Indexed for MEDLINE]
Free PMC Article

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