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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 )
Author(s) -
Souquière Sandrine,
MouingaOndeme Augustin,
Makuwa Maria,
Beggio Paola,
Radaelli Antonia,
De Giuli Morghen Carlo,
Mortreux Franck,
Kazanji Mirdad
Publication year - 2009
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/j.1600-0684.2009.00356.x
Subject(s) - biology , tropism , simian , virology , provirus , cd8 , t cell , cytokine , immune system , virus , immunology , cytotoxic t cell , viral load , in vitro , gene , biochemistry , genome
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.