Rapid, complex adaption of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression.
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Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
Wolters Kluwer Health.
Abstract
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.
Description
CAPRISA 2013.
Keywords
Acute infection., Africa., Cytotoxic T-lymphocytes., Genome., HIV-1., Progression.
Citation
Abrahams, M.R., Treurnicht, F.K., Ngandu, N.K., Goodier, S.A., Marais, J.C., Bredell, H., Thebus, R., de Assis Rosa, D., Mlisana, K., Seoighe, C. and Abdool Karim, S.S. 2013. Rapid, complex adaption of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression. AIDS (London, England) 27(4), 507-518.