Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit

Chu Wang; Donglai Liu; Tao Zuo; Bhavna Hora; Fangping Cai; Haitao Ding; John Kappes; Christina Ochsenbauer; Wei Kong; Xianghui Yu; Tanmoy Bhattacharya; Alan S Perelson; Feng Gao

doi:10.1016/j.jinf.2019.12.001

Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit

J Infect. 2020 Feb;80(2):210-218. doi: 10.1016/j.jinf.2019.12.001. Epub 2019 Dec 5.

Authors

Chu Wang¹, Donglai Liu², Tao Zuo¹, Bhavna Hora³, Fangping Cai³, Haitao Ding⁴, John Kappes⁴, Christina Ochsenbauer⁴, Wei Kong⁵, Xianghui Yu⁵, Tanmoy Bhattacharya⁶, Alan S Perelson⁶, Feng Gao⁷

Affiliations

¹ National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
² National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Division of the Second in Vitro Diagnostic, National Institute for Food and Drug Control, Beijing 100050, China.
³ Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
⁴ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁵ National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China.
⁶ Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
⁷ National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: fgao@duke.edu.

Abstract

Objective: Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early infection affect viral fitness has not been well studied.

Methods: Paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection were generated from 10 infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo viruses to their cognate T/F viruses.

Results: All ten 6-mo viruses were less fit than their cognate T/F viruses. Moreover, the fitness losses of the 6-mo viruses correlated with the decrease in viral loads from the peak of viremia.

Conclusion: These results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.

Keywords: Fitness; HIV-1; Infection; Mutation; Transmitted/founder virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

HIV Infections*
HIV Seropositivity*
HIV-1* / genetics
Humans
Mutation
Viral Load
Virus Replication

Abstract

Publication types

MeSH terms

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