title: Comprehensive analyses of a unique HIV-1-infected nonprogressor reveal a complex association of immunobiological mechanisms in the context of replication-incompetent infection.
abstract: We recently demonstrated that a unique HIV-1-infected nonprogressor was infected with a nonevolving replication-incompetent HIV-1 strain, showing a total absence of viral evolution in vivo. Potent immune responses against HIV-1 were observed in his PBMC, despite an apparent lack of viral replication for at least 8 years. His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains, although highly purified CD4+ T cells supported infection, but without any visible cytopathic effect. Potent noncytolytic CD8+ T cell antiviral activity was shown to protect his PBMC from productive infection. This activity was not mediated by several known chemokines or IFN-gamma, which were produced at high levels after PHA activation of his CD8+ T cells, indicating the action of other CAF-like CD8 factors. This antiviral activity was a memory response, induced by HIV-specific stimulation to similar levels observed by PHA stimulation, but absent in ex vivo resting T cells. Immunological mechanisms associated with this antiviral suppressive activity included vigorous Gag-specific helper T cell proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T cells. These responses were broadly directed against multiple Gag epitopes, both previously reported and some novel epitopes. Strong HIV-specific helper T cell function was also associated with strong neutralizing antibodies. Understanding how to induce these protective immune responses in other individuals could provide a major step forward in the design of effective immunotherapies or vaccines against HIV infection.
authors.affiliation: Retroviral Genetics Laboratory, Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Westmead, New South Wales 2145, Australia.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Dyer
authors.forename: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Meriet
authors.initials: M
authors.lastname: Mikhail
authors.forename: John S
authors.initials: JS
authors.lastname: Sullivan
authors.forename: Lisa
authors.initials: L
authors.lastname: Williams
authors.forename: Da'ed N
authors.initials: DN
authors.lastname: Haddad
authors.forename: Graeme
authors.initials: G
authors.lastname: Harris
authors.forename: John A G
authors.initials: JA
authors.lastname: Holt
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Monica
authors.initials: M
authors.lastname: Miranda-Saksena
authors.forename: Ross
authors.initials: R
authors.lastname: Boadle
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication
chemical_list: C515334:CCR2 protein, human; D018925:Chemokines; D016207:Cytokines; D015483:HIV Antibodies; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine