title: Enhanced replication of M-tropic HIV-1 strains in Herpesvirus saimiri immortalised T-cells which express CCR5.
abstract: A better characterisation of mononuclear cell-tropic (M-tropic) HIV-1 is central to disease control as these viruses predominate in disease transmission. M-tropic viruses do not replicate in conventional T-cell lines, and virus titres obtained in peripheral blood mononuclear cells (PBMC) are low. Human T-lymphocytes which have been immortalised by Herpesvirus saimiri strain C488 (HVS T-cells) are highly permissive to the replication of T-cell tropic strains of HIV. This study aimed to determine if HVS T-cells support replication of M-tropic HIV isolates that have not been adapted to conventional T-cell lines. A panel of PBMC low passage/primary field isolates and their molecular clones was used. Results show that infection in HVS T-cells was longer lived than in PBMC. In terms of peak virus titre and duration of productive 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 further biological studies such as virus neutralisation, co receptor usage and testing 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 HIV-1 in vivo.
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002472:Cell Transformation, Viral; D018946:Chemokine CCL5 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015497:HIV-1 / Q000502:physiology*; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000821:virology; D018523:Tropism / Q000502:physiology; D014779:Virus Replication