HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women

Costello, Caroline; Tang, Jianming; Rivers, Charles A.; Karita, Etienne; Meizen-Derr, Jareen; Allen, Susan; Kaslow, Richard A.

doi:10.1097/00002030-199910010-00031

Cited by 95 publications

(71 citation statements)

References 19 publications

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“…Thus, humoral immunity is probably not the explanation for the nonprogression in these patients. ES1 and ES8 are positive for the HLA-B‫72ء‬ and HLA-B‫75ء‬ allele groups, which are over-represented in LTNP (9,13,25,26,28,36) and ES (41). HLA-B‫44ء‬ has not been associated with slow progression, but three of the four ES had this allele.…”

Section: Discussionmentioning

confidence: 95%

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

Blankson

Bailey

Thayil

et al. 2007

J Virol

242

245

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Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who control viremia to levels below the limit of detection of current assays. The mechanisms involved in this control have not been fully elucidated. Several studies have demonstrated that some ES are infected with defective viruses, but it remains unclear whether others are infected with replication-competent HIV-1. To answer this question, we used a sensitive coculture assay in an attempt to isolate replication-competent virus from a cohort of 10 ES. We successfully cultured six replication-competent isolates from 4 of the 10 ES. The frequency of latently infected cells in these patients was more than a log lower than that seen in patients on highly active antiretroviral therapy with undetectable viral loads. Full-length sequencing of all six isolates revealed no large deletions in any of the genes. A few mutations and small insertions and deletions were found in some isolates, but phenotypic analysis of the affected genes suggested that their function remained intact. Furthermore, all six isolates replicated as well as standard laboratory strains in vitro. The results suggest that some ES are infected with HIV-1 isolates that are fully replication competent and that long-term immunologic control of replication-competent HIV-1 is possible.

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Section: Discussionmentioning

confidence: 95%

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

Blankson

Bailey

Thayil

et al. 2007

J Virol

242

245

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“…Interestingly, HLA-B*57 has also been associated with slow progression of HIV-1 disease in different ethnic populations (8,15); thus, this allele may have some protective activity in a variety of chronic viral illnesses. Alternatively, HLA-B*57 may be in linkage disequilibrium with a gene that promotes elimination of viral infections.…”

Section: Discussionmentioning

confidence: 99%

HLA-Cw04* and Hepatitis C Virus Persistence

Thio¹,

Gao

Goedert

et al. 2002

J Virol

169

165

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In studies of acute hepatitis C virus (HCV) infectionHepatitis C virus (HCV) is an important blood-borne pathogen that is eliminated from the host in approximately 15% of acutely infected individuals while persisting in the remaining 85% of acutely infected individuals (1, 26). The factors involved in viral clearance are not understood, but many studies suggest host differences are critical. Of 704 Irish women who were accidentally infected with the same viral inoculum (contaminated immunoglobulin D antibody), 314 (45%) cleared their infection (13). Likewise, 43% of 152 German women cleared their infection after being exposed to the same contaminated lot of immunoglobulin D antibody (16). Since the women in their respective studies received the same virus, viral diversity cannot account for the dichotomy in outcome, rather differences in host response were likely the determining factor. Another study found marked differences in the frequency of viral clearance in Caucasians and African-Americans (21). The breadth and vigor of the host cellular immune response correlated with viral clearance in a study of six chimpanzees (6). Similarly, studies in humans have shown that a stronger polyclonal cytotoxic T lymphocyte (CTL) response is associated with viral clearance (18).The class I and class II human leukocyte antigens (HLA) are central to the host immune response and thus are ideal candidate genes to investigate for associations with HCV outcomes. Class I and class II HLA are encoded by the most polymorphic genes known and present antigen to CD8 ϩ cytotoxic T cells and CD4 ϩ helper T cells, respectively. Polymorphisms in the peptide binding regions of these molecules determine antigenic specificities and the strength of the immune response to a given pathogen. Certain HLA alleles have been shown to influence the outcome of other chronic viral infections (12,19,23), and a few recent studies examined class II HLA alleles in the context of HCV clearance (3,20,22,25). Given the importance of the cellular immune response in HCV infection, it is reasonable to postulate that certain HLA class I molecules may present HCV epitopes to cytotoxic T cells, resulting in a protective immune response, whereas other types may participate less efficiently in clearance of the virus. To date, this hypothesis has not been investigated; thus, using three distinct cohorts of individuals, we examined whether particular HLA class I alleles are predisposing factors to either HCV clearance or persistence.

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“…Of the MHC class I alleles also associated with prolonged AIDS-free survival, HLA-B*27 and HLA-B*57 have been consistently described (10,(12)(13)(14)(15). The GAG p24-derived B*2705-restricted epitope (KRWIILGLNK), is highly immunodominant and induces a potent CD8 ϩ T cell-mediated immune response consistent with slower onset of AIDS in HIV-1-infected donors.…”

Section: P Articularly During Acute Infection (1-4) Cd8mentioning

confidence: 99%

Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression

Stewart‐Jones

Gillespie

Overton

et al. 2005

The Journal of Immunology

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Long-term nonprogression during acute HIV infection has been strongly associated with HLA-B*5701 or HLA-B*5703. In this study, we present the high resolution crystal structures of HLA-B*5703 complexes with three HIV-1 epitopes: ISPRTLNAW (ISP), KAFSPEVIPMF (KAF-11), and KAFSPEVI (KAF-8). These reveal peptide anchoring at position 2 and their C termini. The different peptide lengths and primary sequences are accommodated by variation in the specific contacts made to the HLA-B*5703, flexibility in water structure, and conformational adjustment of side chains within the peptide-binding groove. The peptides adopt markedly different conformations, and trap variable numbers of water molecules, near a cluster of tyrosine side chains located in the central region of the peptide-binding groove. The KAF-11 epitope completely encompasses the shorter KAF-8 epitope but the peptides are presented in different conformations; the KAF-11 peptide arches out of the peptide-binding groove, exposing a significant main chain surface area. Bioinformatic analysis of the MHC side chains observed to contribute to the peptide anchor specificity, and other specific peptide contacts, reveals HLA alleles associated with long-term nonprogression and a number of related HLA alleles that may share overlapping peptide repertoires with HLA-B*5703 and thus may display a similar capacity for efficient immune control of HIV-1 infection.

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HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women

Cited by 95 publications

References 19 publications

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

HLA-Cw04* and Hepatitis C Virus Persistence

Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression

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HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women

Cited by 95 publications

References 19 publications

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

HLA-Cw*04 and Hepatitis C Virus Persistence

Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression

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Product

Resources

About

HLA-Cw04* and Hepatitis C Virus Persistence