Effective activation alleviates the replication block of CCR5-tropic HIV-1 in chimpanzee CD4+ lymphocytes

• Published in: Virology (New York, N.Y.) Vol. 394; no. 1; pp. 109 - 118
• Main Authors: Decker, Julie M, Zammit, Kenneth P, Easlick, Juliet L, Santiago, Mario L, Bonenberger, Denise, Hahn, Beatrice H, Kutsch, Olaf, Bibollet-Ruche, Frederic
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.11.2009
• Subjects: Activation; Animals; CCR5; CD4 antigen; CD4+ lymphocytes; CD4-Positive T-Lymphocytes - virology; CD62L protein; Cell activation; Cells, Cultured; Chimpanzee; CXCR4 protein; Histocompatibility antigen HLA; HIV Core Protein p24 - biosynthesis; HIV-1; HIV-1 - growth & development; HLA-DR Antigens - metabolism; Human immunodeficiency virus 1; Humans; Infectious Disease; L-Selectin - metabolism; Lymphocyte Activation; Lymphocytes T; Pan troglodytes; Replication; HIV-1; CD4+ lymphocytes; Activation; CCR5; Chimpanzee
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.08.027

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.