Abstract
Human immunodeficiency virus type 1 (HIV-1)-infected persons who maintain plasma viral loads of <50 copies RNA/ml without treatment have been termed elite controllers (EC). Factors contributing to durable control of HIV in EC are unknown, but an HLA-dependent mechanism is suggested by overrepresentation of "protective" class I alleles, such as B*27, B*51, and B*57. Here we investigated the relative replication capacity of viruses (VRC) obtained from EC (n = 54) compared to those from chronic progressors (CP; n = 41) by constructing chimeric viruses using patient-derived gag-protease sequences amplified from plasma HIV RNA and inserted into an NL4-3 backbone. The chimeric viruses generated from EC displayed lower VRC than did viruses from CP (P < 0.0001). HLA-B*57 was associated with lower VRC (P = 0.0002) than were other alleles in both EC and CP groups. Chimeric viruses from B*57(+) EC (n = 18) demonstrated lower VRC than did viruses from B*57(+) CP (n = 8, P = 0.0245). Differences in VRC between EC and CP were also observed for viruses obtained from individuals expressing no described "protective" alleles (P = 0.0065). Intriguingly, two common HLA alleles, A*02 and B*07, were associated with higher VRC (P = 0.0140 and 0.0097, respectively), and there was no difference in VRC between EC and CP sharing these common HLA alleles. These findings indicate that cytotoxic T-lymphocyte (CTL) selection pressure on gag-protease alters VRC, and HIV-specific CTLs inducing escape mutations with fitness costs in this region may be important for strict viremia control in EC of HIV.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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HIV-1 / immunology
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HIV-1 / physiology*
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HLA Antigens / genetics*
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HLA Antigens / metabolism
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Humans
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Molecular Sequence Data
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Mutation
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Phylogeny
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RNA, Viral / genetics
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Recombination, Genetic
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Selection, Genetic
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Sequence Analysis, DNA
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Sequence Homology
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T-Lymphocytes, Cytotoxic / immunology
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Virus Replication*
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gag Gene Products, Human Immunodeficiency Virus / genetics*
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gag Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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HLA Antigens
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RNA, Viral
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gag Gene Products, Human Immunodeficiency Virus
Associated data
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GENBANK/EU864042
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GENBANK/EU864043
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GENBANK/EU864044
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GENBANK/EU864045
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GENBANK/EU864046
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