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

  • Author Footnotes
    1 These two authors contributed equally to this work.
    Chu Wang
    Footnotes
    1 These two authors contributed equally to this work.
    Affiliations
    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
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  • Author Footnotes
    1 These two authors contributed equally to this work.
    Donglai Liu
    Footnotes
    1 These two authors contributed equally to this work.
    Affiliations
    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
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  • Tao Zuo
    Affiliations
    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
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  • Bhavna Hora
    Affiliations
    Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
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  • Fangping Cai
    Affiliations
    Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
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  • Haitao Ding
    Affiliations
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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  • John Kappes
    Affiliations
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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  • Christina Ochsenbauer
    Affiliations
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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  • Wei Kong
    Affiliations
    National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China
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  • Xianghui Yu
    Affiliations
    National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China
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  • Tanmoy Bhattacharya
    Affiliations
    Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
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  • Alan S Perelson
    Affiliations
    Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
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  • Feng Gao
    Correspondence
    Corresponding author at: Department of Medicine, Duke University Medical Center, 244 Sands Building, 303 Research Drive, DUMC 102359, Durham, NC 27710, USA.
    Affiliations
    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
    Search for articles by this author
  • Author Footnotes
    1 These two authors contributed equally to this work.
Published:December 05, 2019DOI:https://doi.org/10.1016/j.jinf.2019.12.001

      Highlights

      • Mutations in early HIV-1-infection collectively impair fitness of the T/F viruses.
      • Fitness loss is associated with reduced viral loads from viremia peak.
      • Testing mutations in the cognate T/F genome accurately determinates HIV-1 fitness.

      Summary

      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

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