Enhanced replication of M-tropic HIV-1 strains in Herpesvirus saimiri immortalised T-cells which express CCR5

A better characterisation of mononuclear cell-tropic (M-tropic) HIV-1 is ce ntral to disease control as these viruses predominate in disease transmissi on. M-tropic viruses do not replicate in conventional T-cell lines, and vir us titres obtained in peripheral blood mononuclear cells (PBMC) are low. Hu man T-lymphocytes which have been immortalised by Herpesvirus saimiri strai n C488 (HVS T-cells) are highly permissive to the replication of T-cell tro pic strains of HIV. This study aimed to determine if HVS T-cells support re plication of M-tropic HIV isolates that have not been adapted to convention al T-cell lines. A panel of PBMC low passage/primary field isolates and the ir molecular clones was used. Results show that infection in HVS T-cells wa s longer lived than in PBMC. In terms of peak virus titre and duration of p roductive infection, the two HVS T-cell lines studied were superior to PBMC , and one supported enhanced replication of all M-tropic isolates. This is important for generating M-tropic virus pools of sufficient titre for furth er biological studies such as virus neutralisation, co recptor usage and te sting of antivirals. Phenotypic analysis showed that HVS T-cells are CD4(+) -activated memory cells expressing both CXCR-4 and CCR5 co receptors. Thus, HVS immortalisation appears to select for the T-cell subset targeted by HI V-I in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.