title: Transmission of human immunodeficiency virus type 1 from a patient who developed AIDS to an elite suppressor.
abstract: Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml. The mechanisms involved in this control of viral replication remain unclear. Prior studies suggested that these patients, as well as long-term nonprogressors, are infected with defective HIV-1 variants. Other reports have shown that the HLA-B*27 and -B*57 alleles are overrepresented in these patients, suggesting that host factors play a role in the control of viral replication. In order to distinguish between these hypotheses, we studied differences in viral isolates and immune responses of an HIV-1 transmission pair. While both patients are HLA-B*57 positive, the transmitter progressed to AIDS, whereas the recipient, who is also HLA-B*27 positive, is an ES. Isolates from both patients were replication competent and contained the T242N escape mutation in Gag, which is known to decrease viral fitness. While the acquisition of compensatory mutations occurred in isolates from the progressor, a superior HIV-specific CD8(+) T-cell response in the ES appears to have prevented viral replication and thus the evolution toward a more fit variant. In addition, CD8(+) T cells in the ES have selected for a rare mutation in an immunodominant HLA-B*27-restricted Gag epitope, which also has a negative impact on fitness. The results strongly suggest that through direct and indirect mechanisms, CD8(+) T cells in some ES control HIV-1 isolates are capable of causing profound immunosuppression.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Bailey
authors.forename: Karen
authors.initials: K
authors.lastname: O'Connell
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Yefei
authors.initials: Y
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jilek
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Williams
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: Joel N
authors.initials: JN
authors.lastname: Blankson
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission* / Q000821:virology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D015796:HLA-B27 Antigen; D054301:gag Gene Products, Human Immunodeficiency Virus