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-gamma and tumour necrosis factor-alpha. 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.
Souquière
Sandrine
S
Département de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
Mouinga-Ondeme
Augustin
A
Makuwa
Maria
M
Beggio
Paola
P
Radaelli
Antonia
A
De Giuli Morghen
Carlo
C
Mortreux
Franck
F
Kazanji
Mirdad
M
D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D048528:Mandrillus; D016133:Polymerase Chain Reaction / Q000662:veterinary; D015303:Simian T-lymphotropic virus 1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019562:Viral Load
D000906:Antibodies; D016207:Cytokines