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Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10

Open access
Shin, Hyoung Doo, Winkler, Cheryl, Stephens, J. Claiborne, Bream, Jay, Young, Howard, Goedert, James J., O'Brien, Thomas R., Vlahov, David, Buchbinder, Susan, Giorgi, Janis, Rinaldo, Charles, Donfield, Sharyne, Willoughby, Anne, O'Brien, Stephen J., Smith, Michael W.·2000·Proceedings of the National Academy of Sciences

Abstract

IL10 is a powerful TH-2 cell cytokine produced by lymphoid cells that limits HIV-1 replication in vivo , ostensibly by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFα, IL6, IL8, and IL12). A genetic epidemiological scan of patients enrolled in AIDS cohorts for candidate gene-linked short tandem repeat polymorphisms revealed significant genotype associations for HIV-1 infection and progression to AIDS with markers adjacent to and tracking (by linkage disequilibrium) common single nucleotide polymorphic variants in the IL10 promoter region. Individuals carrying the IL10-5′−592A ( IL10-5′A ) promoter allele possibly were at increased risk for HIV-1 infection, and once infected they progressed to AIDS more rapidly than homozygotes for the alternative IL10-5′−592 C/C ( IL10 -+/+) genotype, particularly in the later stages of HIV-1 infection. An estimated 25–30% of long-term nonprogressors (who avoid clinical AIDS for 10 or more years after HIV-1 infection) can be attributed to their IL10 -+/+ promoter genotype. Alternative IL10 promoter alleles are functionally distinct in relative IL10 production, in retention of an avian erythroblastosis virus transcription factor recognition sequence and in binding to specific putative nuclear transcription factors, suggesting a potential mechanism whereby IL10-5′A down-regulation of inhibitory IL10 facilitates HIV-1 replication in vivo , accelerating the onset of AIDS.

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Metadata

Authors
Shin, H. D., Winkler, C., Stephens, J. C., Bream, J., Young, H., Goedert, J. J., O'Brien, T. R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinaldo, C., Donfield, S., Willoughby, A., O'Brien, S. J., & Smith, M. W.
Venue
Proceedings of the National Academy of Sciences
Published
2000-12-19
Volume
97
Issue
26
Pages
14467-14472
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2140865115
Cited by
286
References
51
FWCI
3.99
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. https://app.cochat.ai/papers/10.1073/pnas.97.26.14467
The paper
Shin, H. D., Winkler, C., Stephens, J. C., Bream, J., Young, H., Goedert, J. J., O'Brien, T. R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinaldo, C., Donfield, S., Willoughby, A., O'Brien, S. J., & Smith, M. W. (2000). Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.97.26.14467

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.