The immune control and cell-to-cell spread of human T-lymphotropic virus type 1.
Human T-lymphotropic virus type 1 (HTLV-1) varies little in sequence compared with human immunodeficiency virus type 1 (HIV) and it is difficult to detect HTLV-1 mRNA, proteins or virions in fresh blood. But the strong and chronically activated T cell response to the virus indicates that HTLV-1 proteins are expressed persistently. It now appears that the efficiency of an individual's cytotoxic T cell (CTL) response to HTLV-1 is the chief single determinant of that person's provirus load, which can differ between HTLV-1-infected people by more than 10 000-fold. Progress is now being made towards defining this CTL 'efficiency' in terms of host genetics, T cell function, T cell gene expression and mathematical dynamics. Lymphocytes that are naturally infected with HTLV-1 do not produce enveloped extracellular virions in short-term culture and this has reinforced the erroneous conclusion that the virus is latent. But recent evidence shows that HTLV-1 can spread directly between lymphocytes across a specialized, virus-induced cell-cell contact - a 'viral synapse'. Instead of making extracellular virions, HTLV-1 uses the mobility of the host cell to spread within and between hosts. In this review the evidence is summarized on the persistent gene expression of HTLV-1 in vivo, the role of the immune system in protection and pathogenesis in HTLV-1 infection, and the mechanism of cell-to-cell spread of HTLV-1.
Bangham
Charles R M
CRM
Wright-Fleming Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015686:Gene Products, env / Q000032:analysis; D015683:Gene Products, gag / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007365:Intercellular Junctions / Q000821:virology; D016015:Logistic Models; D018655:Lymphocyte Count; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D011533:Proviruses / Q000472:pathogenicity; D012194:RNA-Directed DNA Polymerase / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D019562:Viral Load; D017735:Virus Latency
D015686:Gene Products, env; D015683:Gene Products, gag; D012194:RNA-Directed DNA Polymerase