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

JM Decker, KP Zammit, JL Easlick, ML Santiago… - Virology, 2009 - Elsevier
JM Decker, KP Zammit, JL Easlick, ML Santiago, D Bonenberger, BH Hahn, O Kutsch…
Virology, 2009Elsevier
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 …
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.
Elsevier