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HIV-1 DNA sequence diversity and evolution during acute subtype C infection

Author

Listed:
  • Guinevere Q. Lee

    (Ragon Institute of MGH, MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Kavidha Reddy

    (University of KwaZulu-Natal
    Africa Health Research Institute)

  • Kevin B. Einkauf

    (Ragon Institute of MGH, MIT and Harvard
    Brigham and Women’s Hospital)

  • Kamini Gounder

    (University of KwaZulu-Natal
    Africa Health Research Institute)

  • Joshua M. Chevalier

    (Ragon Institute of MGH, MIT and Harvard)

  • Krista L. Dong

    (Ragon Institute of MGH, MIT and Harvard
    Harvard Medical School)

  • Bruce D. Walker

    (Ragon Institute of MGH, MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School
    University of KwaZulu-Natal)

  • Xu G. Yu

    (Ragon Institute of MGH, MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Thumbi Ndung’u

    (Ragon Institute of MGH, MIT and Harvard
    University of KwaZulu-Natal
    Africa Health Research Institute
    Max Planck Institute for Infection Biology)

  • Mathias Lichterfeld

    (Ragon Institute of MGH, MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

Abstract

Little is known about the genotypic make-up of HIV-1 DNA genomes during the earliest stages of HIV-1 infection. Here, we use near-full-length, single genome next-generation sequencing to longitudinally genotype and quantify subtype C HIV-1 DNA in four women identified during acute HIV-1 infection in Durban, South Africa, through twice-weekly screening of high-risk participants. In contrast to chronically HIV-1-infected patients, we found that at the earliest phases of infection in these four participants, the majority of viral DNA genomes are intact, lack APOBEC-3G/F-associated hypermutations, have limited genome truncations, and over one year show little indication of cytotoxic T cell-driven immune selections. Viral sequence divergence during acute infection is predominantly fueled by single-base substitutions and is limited by treatment initiation during the earliest stages of disease. Our observations provide rare longitudinal insights of HIV-1 DNA sequence profiles during the first year of infection to inform future HIV cure research.

Suggested Citation

  • Guinevere Q. Lee & Kavidha Reddy & Kevin B. Einkauf & Kamini Gounder & Joshua M. Chevalier & Krista L. Dong & Bruce D. Walker & Xu G. Yu & Thumbi Ndung’u & Mathias Lichterfeld, 2019. "HIV-1 DNA sequence diversity and evolution during acute subtype C infection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10659-2
    DOI: 10.1038/s41467-019-10659-2
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    Cited by:

    1. Guinevere Q. Lee & Pragya Khadka & Sarah N. Gowanlock & Dennis C. Copertino & Maggie C. Duncan & F. Harrison Omondi & Natalie N. Kinloch & Jingo Kasule & Taddeo Kityamuweesi & Paul Buule & Samiri Jami, 2024. "HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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