Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
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.


RESULTS
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 B consensus sequence.


CONCLUSIONS
The relatively high proportion of long-term preserved mutations after transmission points to a lack of back selection even in the absence of CTL pressure, which may lead to an accumulating loss of critical CTL epitopes. Our data are supportive for a continuous adaptation of HIV-1 to host immune pressures which may have implications for vaccine design.
Navis
Marjon
M
Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Matas
Diana Edo
DE
Rachinger
Andrea
A
Koning
Fransje A
FA
van Swieten
Peter
P
Kootstra
Neeltje A
NA
Schuitemaker
Hanneke
H
D001483:Base Sequence; D017931:DNA Primers; D019143:Evolution, Molecular; D015497:HIV-1 / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D014019:Tissue Donors
D017931:DNA Primers; D006680:HLA Antigens; D012367:RNA, Viral