Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Abstract
Antigen-specific T cell immunity is HLA-restricted. Human immunodeficiency virus–type 1 (HIV-1) mutations that allow escape from host immune responses may therefore be HLA allele–specific. We analyzed HIV-1 reverse transcriptase sequences from a large HLA-diverse population of HIV-1–infected individuals. Polymorphisms in HIV-1 were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA class I alleles. Absence of polymorphism was also HLA allele–specific. At a population level, the degree of HLA-associated selection in viral sequence was predictive of viral load. These results support a fundamental role for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo.
Get full access to this article
View all available purchase options and get full access to this article.
Supplementary Material
REFERENCES AND NOTES
1
McMichael A. J., Rowland-Jones S. L., Nature 410, 980 (2001).
2
Evans D. T., et al., Nature Med. 5, 1270 (1999).
3
Allen T. M., et al., Nature 407, 386 (2000).
4
Barouch D. H., et al., Nature 415, 335 (2002).
5
Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H., Cell 66, 1145 (1991).
6
Wrobel J. A., et al., Proc. Natl. Acad. Sci. U.S.A. 95, 638 (1998).
7
Layne S. P., et al., Virology 189, 695 (1992).
8
Walker B. D., et al., Science 240, 64 (1988).
9
Hosmalin A., et al., Proc. Natl. Acad. Sci U.S.A. 87, 2344 (1990).
10
Mallal S. A., J. AIDS Hum. Retrovirol. 17, S23 (1998).
11
The Western Australian HIV Cohort Study is a prospective observational cohort study of HIV-infected patients that was established in 1983. Comprehensive demographic, clinical, and laboratory data are collected on all individuals and maintained in an electronic database. Participants in the cohort typically have had HIV-1 RT proviral DNA sequencing performed at first presentation and before antiretroviral therapy and serially posttreatment as required for clinical care since 1995.
12
HIV-1 DNA was extracted from buffy coats (QIAMP DNA blood mini kit; Qiagen, Hilden, Germany) and codons 20 to 227 of RT were amplified by polymerase chain reaction (PCR). A nested second round PCR was done, and the PCR product was purified with Bresatec purification columns and sequenced in forward and reverse directions with a model 373 ABI DNA sequencer. Raw sequence was manually edited with software packages Factura and MT Navigator (PE Biosystems).
13
All HLA-A and -B broad alleles were typed by the standard National Institutes of Health complement-dependent microtoxicity technique. Fifty-one HLA-B5 individuals and 57 HLA-B35 individuals had HLA-B sequence amplified with primers to the first intronic dimorphism, and products were sequenced by automated sequencing.
14
Ratner L., et al., Nature 313, 277 (1985).
15
For supplementary analyses, detailed description of all statistical methods, and a full version of Fig. 1, see ScienceOnline at www.sciencemag.org/cgi/content/full/296/5572/1439/DC1.
16
F. L. Ramsey, D. W. Schafer, in The Statistical Sleuth. A Course in Methods of Data Analysis (Duxbury Press, Belmont, CA 1997), pp. 10–13, chap. 1.3.
17
B. T. M. Korber et al., HIV Molecular Immunology Database 1999 (Theoretical Biology and Biophysics, Los Alamos, New Mexico, 1999).
18
Kuttler C., et al., J. Mol. Biol. 298, 417 (2000).
19
de Groot A. S., et al., AIDS Res. Hum. Retroviruses 13, 529 (1997).
20
Sipsas N. V., et al., J. Clin. Invest. 99, 752 (1997).
21
Wagner L., et al., Nature 391, 908 (1998).
22
Campos-Lima P. O., et al., Science 260, 98 (1993).
23
Campos-Lima P. O., Levitsky V., Imreh M. P., Gavioli R., Masucci M. G., J. Exp. Med. 186, 83 (1997).
24
Hay C. M., et al., J. Virol. 73, 5509 (1999).
25
Brander C., et al., J. Clin. Invest. 101, 2559 (1998).
26
Shankar P., Sprang H., Lieberman J., J. AIDS Hum. Retrovirol. 19, 111 (1998).
27
Rowland-Jones S., et al., Nature Med. 1, 59 (1995).
28
Fowke K. R., et al., Lancet 348, 1347 (1996).
29
Rowland-Jones S. L., et al., J. Clin. Invest. 102, 1758 (1998).
30
Rowland-Jones S. L., et al., Immunol. Lett. 66, 9 (1999).
31
Mazzoli S., et al., Nature Med. 3, 1250 (1997).
32
Fabio G., et al., Clin. Exp. Immunol. 87, 20 (1992).
33
The viral load assay used until November 1999 was the HIV Amplicor (Roche Diagnostics, Branchburg, NJ) (lower limit of detection, 400 copies per ml). The Roche Amplicor HIV monitor version 1.5, Ultrasensitive (lower limit of detection, 50 copies per ml) was used thereafter.
34
Goulder P. J. R., et al., Immunol. Rev. 159, 17 (1997).
35
Schmitt M., et al., AIDS 14, 653 (2000).
36
We are indebted to participants in the WA HIV Cohort Study as well as past and present clinical and laboratory staff of the Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Western Australia. We thank S. Rowland-Jones for helpful comments on the manuscript. C.B.M. was recipient of an Australian Postgraduate Award, and M.J. is recipient of a National Health and Medical Research Council of Australia Postgraduate Scholarship.
(0)eLetters
eLetters is a forum for ongoing peer review. eLetters are not edited, proofread, or indexed, but they are screened. eLetters should provide substantive and scholarly commentary on the article. Embedded figures cannot be submitted, and we discourage the use of figures within eLetters in general. If a figure is essential, please include a link to the figure within the text of the eLetter. Please read our Terms of Service before submitting an eLetter.
Log In to Submit a ResponseNo eLetters have been published for this article yet.
Information & Authors
Information
Published In
Science
Volume 296 | Issue 5572
24 May 2002
24 May 2002
Submission history
Received: 9 January 2002
Accepted: 27 March 2002
Published in print: 24 May 2002
Authors
Metrics & Citations
Metrics
Article Usage
Altmetrics
Citations
Cite as
- Corey B. Moore et al.
Export citation
Select the format you want to export the citation of this publication.
Cited by
- Sequence diversity of hepatitis D virus in Mongolia, Frontiers in Medicine, 10, (2023).https://doi.org/10.3389/fmed.2023.1108543
- Single-cycle influenza virus vaccine generates lung CD8+ Trm that cross-react against viral variants and subvert virus escape mutants, Science Advances, 9, 36, (2023)./doi/10.1126/sciadv.adg3469
- Nano-vaccines for gene delivery against HIV-1 infection, Expert Review of Vaccines, 22, 1, (315-326), (2023).https://doi.org/10.1080/14760584.2023.2193266
- Baseline QOL, QOL-relevant HLA-restricted HERV gene-derived peptides, and survival outcomes in gastric cancer, Annals of Cancer Research and Therapy, 30, 2, (55-66), (2022).https://doi.org/10.4993/acrt.30.55
- On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses, Viruses, 15, 1, (70), (2022).https://doi.org/10.3390/v15010070
- High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort, Viruses, 14, 2, (273), (2022).https://doi.org/10.3390/v14020273
- Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains, PLOS Pathogens, 18, 12, (e1010965), (2022).https://doi.org/10.1371/journal.ppat.1010965
- HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients , Journal of Virology, 96, 17, (2022).https://doi.org/10.1128/jvi.01191-22
- Next-generation T cell–activating vaccination increases influenza virus mutation prevalence, Science Advances, 8, 14, (2022)./doi/10.1126/sciadv.abl5209
- SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity, Virus Evolution, 8, 2, (2022).https://doi.org/10.1093/ve/veac106
- See more
Loading...
View Options
Check Access
Log in to view the full text
AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.
- Become a AAAS Member
- Activate your AAAS ID
- Purchase Access to Other Journals in the Science Family
- Account Help
Log in via OpenAthens.
Log in via Shibboleth.
More options
Purchase digital access to this article
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.