molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs分子进化的人类免疫缺陷病毒1型传播人类白细胞抗原不同的捐助者与接受者之间对.pdfVIP

Molecular Evolution of Human Immunodeficiency Virus Type 1 upon Transmission between Human Leukocyte Antigen Disparate Donor-Recipient Pairs ¤ Marjon Navis, Diana Edo Matas, Andrea Rachinger, Fransje A. Koning , Peter van Swieten, Neeltje A. Kootstra, Hanneke Schuitemaker* Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands Abstract Background: To address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methodology/Principal Findings: In the first weeks after transmission, the majority of donor-derived mutations in and outside donor-HLA-restricted epitopes in Gag, Env, and Nef, were preserved in the recipient. Reversion to the HIV-1 subtype B consensus sequence of mutations in- and outside donor-HLA-restricted CTL epitopes, and new mutations away from the consensus B sequence mostly within recipient-HLA-restricted epitopes, contributed equally to the early sequence changes. In the subsequent period (1–2 years) after transmission, still only a low number of both reverting and forward mutations had occurred. During subsequent long-term follow-up, sequence dynamics were dominated by forward mutations, mostly (50–85%) in recipient-HLA-restricted CTL epitopes. At the end of long-term follow-up, on average 43% of the transmitted CTL escape mutations in donor-HLA-restricted epitopes had reverted to the subtype