Rapid, complex adaption of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression.

CAPRISA 2013.Objective(s): There is limited information on full-length genome sequences and the early evolution of transmitted HIV-1 subtype C viruses, which constitute the majority of viruses spread in Africa. The purpose of this study was to characterize the earliest changes across the genome of subtype C viruses following transmission, to better understand early control of viremia. Design: We derived the near full-length genome sequence responsible for clinical infection from five HIV subtype C-infected individuals with different disease progression profiles and tracked adaptation to immune responses in the first 6 months of infection. Methods: Near full-length genomes were generated by single genome amplification and direct sequencing. Sequences were analyzed for amino acid mutations associated with cytotoxic T lymphocyte (CTL) or antibody-mediated immune pressure, and for reversion. Results: Fifty-five sequence changes associated with adaptation to the new host were identified, with 38% attributed to CTL pressure, 35% to antibody pressure, 16% to reversions and the remainder were unclassified. Mutations in CTL epitopes were most frequent in the first 5 weeks of infection, with the frequency declining over time with the decline in viral load. CTL escape predominantly occurred in nef, followed by pol and env. Shuffling/toggling of mutations was identified in 81% of CTL epitopes, with only 7% reaching fixation within the 6-month period. Conclusion: There was rapid virus adaptation following transmission, predominantly driven by CTL pressure, with most changes occurring during high viremia. Rapid escape and complex escape pathways provide further challenges for vaccine protection

HIV infection in high school students in rural South Africa: role of transmissions among students.

CAPRISA, 2014.Abstract available in pdf

Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition : implications for active and passive immunization.

CAPRISA, 2016.Abstract available in PDF file

Differences in HIV-1 neutralization breadth in two geographically distinct cohorts in Africa.

CAPRISA, 2015.Abstract available in pdf

Maximum likelihood phylogenetic analysis of southern African clade C acute/early envelope nucleotide sequences (n = 200) (Table 1).

<p>Branches are colored according to country/region. Bootstrap values > 80% of 100 resampled replicates are illustrated as filled circles on nodes. South African samples from Soweto/Johannesburg (Gauteng province), Cape Town (Western Cape Province), and KwaZulu-Natal are highlighted in light green, red, and blue respectively, sequences from other locations in South Africa are shown in grey. Clades that were from the same geographic region are highlighted. Only one of these regional grouping (>2 sequence clusters) had strong bootstrap support (4 sequences from Tanzania, highlighted in orange).</p

Geometric mean titer and tier 1A and 1B classification (n = 200).

<p>(A) Viruses are rank ordered according to neutralization sensitivity to 30 clade C chronic infection serum samples, from the least sensitive to the most sensitive along the x-axis by average log₁₀ GMTs. Two viruses were classified as highly sensitive tier 1A and an additional 17 as above-average sensitive tier 1B. A previously determined cut off ID₅₀ = 200, was used to distinguish between tier 1A and tier 1B is indicated on the graph, with tier 1B classified viruses above this cut off colored in red and those below in orange [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005742#ppat.1005742.ref016" target="_blank">16</a>]. Twelve pseudoviruses classified by both Seaman et al., (2010) and this study were found to be discrepant (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005742#ppat.1005742.s009" target="_blank">S1 Table</a>): Du156.12 consistently falls near the boundary of the tier 2 and tier 1B, was classified as tier 1B here however was previously classified as tier 2; and ZM197M and SM109F were classified as tier 2 here, however were previously classified as 1B. (B) Maximum likelihood phylogenetic analysis of southern African clade C acute/early envelope nucleotide sequences (n = 200) with branches colored according to tier. Bootstrap values > 80% of 100 resampled replicates are illustrated as filled circles on nodes.</p