title: Escape from CD8(+) T cell responses in Mamu-B*00801(+) macaques differentiates progressors from elite controllers.
abstract: A small number of HIV-infected individuals known as elite controllers experience low levels of chronic phase viral replication and delayed progression to AIDS. Specific HLA class I alleles are associated with elite control, implicating CD8(+) T lymphocytes in the establishment of these low levels of viral replication. Most HIV-infected individuals that express protective HLA class I alleles, however, do not control viral replication. Approximately 50% of Mamu-B*00801(+) Indian rhesus macaques control SIVmac239 replication in the chronic phase in a manner that resembles elite control in humans. We followed both the immune response and viral evolution in SIV-infected Mamu-B*00801(+) animals to better understand the role of CD8(+) T lymphocytes during the acute phase of viral infection, when viral control status is determined. The virus escaped from immunodominant Vif and Nef Mamu-B*00801-restricted CD8(+) T lymphocyte responses during the critical early weeks of acute infection only in progressor animals that did not control viral replication. Thus, early CD8(+) T lymphocyte escape is a hallmark of Mamu-B*00801(+) macaques who do not control viral replication. By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8(+) T lymphocytes, implying that these cells play a role in viral control.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Mudd
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016384:Consensus Sequence; D018450:Disease Progression; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D016346:Gene Products, vif / Q000276:immunology; D015754:Genes, nef; D016341:Genes, vif; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000276:immunology*
chemical_list: D015693:Gene Products, nef; D016346:Gene Products, vif; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D012367:RNA, Viral