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

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Title: A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies
Authors: Liu, D
Wang, C
Hora, B
Zuo, T
Goonetilleke, N
Liu, MKP
Berrong, M
Ferrari, G
McMichael, AJ
Bhattacharya, T
Perelson, AS
Gao, F
Item Type: Journal Article
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 ftness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in ftness losses. Results: Strongly selected mutations were identifed by analyzing 5′-half HIV-1 genome (gag/pol) sequences from longitudinal samples of subject CH0131. The K43R mutation in the gag gene was frst detected at day 91 post screening and was fxed in the viral population at day 273 while the synonymous N323tc mutation was frst detected at day 177 and fxed at day 670. No conventional or cryptic T cell responses were detected against either mutation sites by ELISpot analysis. However, when ftness costs of both mutations were measured by introducing each mutation into their cognate transmitted/founder (T/F) viral genome, the K43R mutation caused a signifcant ftness loss while the N323tc mutation had little impact on viral ftness. Conclusions: The rapid fxation, the lack of detectable immune responses and the signifcant ftness cost of the K43R mutation suggests that it was strongly selected by host factors other than T cell responses and neutralizing antibodies
Issue Date: 10-Oct-2017
Date of Acceptance: 3-Oct-2017
URI: http://hdl.handle.net/10044/1/52004
DOI: https://dx.doi.org/10.1186/s12977-017-0371-4
ISSN: 1742-4690
Publisher: BioMed Central
Journal / Book Title: Retrovirology
Volume: 14
Copyright Statement: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
Mutation
Selection
Immune responses
Cryptic T cell response
Fitness
Escape
IMMUNODEFICIENCY-VIRUS TYPE-1
ESCAPE MUTATIONS
CLASS-I
LYMPHOCYTE RESPONSE
IMMUNE ESCAPE
SUBTYPE C
FITNESS
GAG
PRESSURE
INFECTION
Cryptic T cell response
Escape
Fitness
Immune responses
Mutation
Selection
Science & Technology
Life Sciences & Biomedicine
Virology
Mutation
Selection
Immune responses
Cryptic T cell response
Fitness
Escape
IMMUNODEFICIENCY-VIRUS TYPE-1
ESCAPE MUTATIONS
CLASS-I
LYMPHOCYTE RESPONSE
IMMUNE ESCAPE
SUBTYPE C
FITNESS
GAG
PRESSURE
INFECTION
1103 Clinical Sciences
Virology
Publication Status: Published
Article Number: 46
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