Rapid, complex adaptation of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression
Autor: | Nobubelo K. Ngandu, Sarah Goodier, Cathal Seoighe, Clive M. Gray, Jinny C. Marais, Koleka Mlisana, Helba Bredell, Debra de Assis Rosa, Ruwayhida Thebus, Melissa-Rose Abrahams, Carolyn Williamson, Florette K. Treurnicht, Salim S. Abdool Karim |
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Rok vydání: | 2013 |
Předmět: |
Immunology
selection cytotoxic t-lymphocytes hiv-1 Viremia medicine.disease_cause Genome Article Epitope Virus rhesus macaques evolution medicine Immunology and Allergy immune-responses genome neutralizing antibody-responses Genetics immunodeficiency-virus type-1 Mutation viremia biology t-cell responses medicine.disease Virology CTL Infectious Diseases africa biology.protein escape progression Antibody acute infection Viral load set-point |
Zdroj: | AIDS. 27:507-518 |
ISSN: | 0269-9370 |
Popis: | 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 thefirst 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. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:507‐518 |
Databáze: | OpenAIRE |
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