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.
Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Marjon
M
Navis
Diana Edo
DE
Matas
Andrea
A
Rachinger
Fransje A
FA
Koning
Peter
P
van Swieten
Neeltje A
NA
Kootstra
Hanneke
H
Schuitemaker
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