title: Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.
abstract: HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Macdonald
authors.initials: M
authors.lastname: Mahiti
authors.affiliation: Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.affiliation: Jessen Praxis, Berlin, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Jessen
authors.affiliation: Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. Electronic address: uenotaka@kumamoto-u.ac.jp.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ueno
mesh_terms: D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D054311:nef Gene Products, Human Immunodeficiency Virus
keywords: HIV-1; HLA class I; HLA class II; Immune evasion; Nef