Effective activation alleviates the replication block of CCR5-tropic HIV-1 in chimpanzee CD4+ lymphocytes.
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.
Decker
Julie M
JM
Department of Medicine, University of Alabama at Birmingham, 720 20th Street South, KAUL 852, Birmingham, AL 35294, USA.
Zammit
Kenneth P
KP
Easlick
Juliet L
JL
Santiago
Mario L
ML
Bonenberger
Denise
D
Hahn
Beatrice H
BH
Kutsch
Olaf
O
Bibollet-Ruche
Frederic
F
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
D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D019041:L-Selectin