title: Effective activation alleviates the replication block of CCR5-tropic HIV-1 in chimpanzee CD4+ lymphocytes.
abstract: Human immunodeficiency virus type 1 (HIV-1) originated in chimpanzees; yet, several previous studies have shown that primary HIV-1 isolates replicate poorly in chimpanzee CD4+ T lymphocytes in vitro and in vivo. The reasons for this apparent restriction are not understood. Here, we describe a new activation protocol that led to a reproducible expansion and activation of chimpanzee CD4+ T lymphocytes in vitro. Using this protocol, we uncovered species-specific differences in the activation profiles of human and chimpanzee CD4+ T-cells, including HLA-DR and CD62L. Moreover, we found that improved activation facilitated the replication of both CXCR4 and CCR5-tropic HIV-1 in CD4+ T-cell cultures from over 30 different chimpanzees. Thus, the previously reported "replication block" of CCR5-tropic HIV-1 in chimpanzee lymphocytes appears to be due, at least in large part, to suboptimal T-cell activation.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 720 20th Street South, KAUL 852, Birmingham, AL 35294, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Zammit
authors.forename: Juliet L
authors.initials: JL
authors.lastname: Easlick
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
authors.forename: Denise
authors.initials: D
authors.lastname: Bonenberger
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Olaf
authors.initials: O
authors.lastname: Kutsch
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation; D002679:Pan troglodytes
chemical_list: D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D019041:L-Selectin