T‐Cell tropism of simian T‐cell leukaemia virus type 1 and cytokine profiles in relation to proviral load and immunological changes during chronic infection of naturally infected mandrills (Mandrillus sphinx)

Background  Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. Methods  We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. Results  With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4+ and CD8+ T cells; however, proviral loads were significantly higher (P = 0.01) in CD4+ than in CD8+ cells (mean STLV-1 copies number per 100 cells (± SD) was 7.8 ± 8 in CD4+ T cells and 3.9 ± 4.5 in CD8+ T cells). After culture, STLV-1 provirus was detected in enriched CD4+ but not in enriched CD8+ T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3+, CD4+ and HLADR+ were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-γ and tumour necrosis factor-α. The two monkeys with the highest STLV-1 proviral load had activated CD4+HLADR+ and CD8+HLADR+ T-cell subsets and a high percentage of CD25+ in CD4+ and CD8+ T cells. Conclusions  Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses.