HIV-1 DNA sequence diversity and evolution during acute subtype C infection.
Guinevere Q LeeKavidha ReddyKevin B EinkaufKamini GounderJoshua M ChevalierKrista L DongBruce D WalkerXu G YuThumbi Ndung'uMathias LichterfeldPublished in: Nature communications (2019)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected patients
- hiv infected
- circulating tumor
- human immunodeficiency virus
- south africa
- hiv aids
- hiv testing
- cell free
- liver failure
- single molecule
- hepatitis c virus
- men who have sex with men
- drug induced
- respiratory failure
- sars cov
- aortic dissection
- magnetic resonance
- magnetic resonance imaging
- cross sectional
- adipose tissue
- dna methylation
- circulating tumor cells
- gene expression
- computed tomography
- skeletal muscle
- extracorporeal membrane oxygenation
- mechanical ventilation
- combination therapy
- replacement therapy