Human T cell leukemia virus type 1 up-regulation after simian immunodeficiency virus-1 coinfection in the nonhuman primate
ABSTRACT The effects that human T cell leukemia virus (HTLV) type 1 and simian immunodeficiency virus (SIV) coinfection have on HTLV-1 dynamics and disease progression were tested in a nonhuman primate model. Seven rhesus macaques were experimentally inoculated with HTLV-1, and a persistent infection was established. Coinfection with SIV/smB670 resulted in increased HTLV-1 p19 antigens in peripheral blood mononuclear cells and HTLV-1 proviral loads. Circulating CD2(+) and CD8(+) T lymphocytes increased over preinoculation levels, along with a progressive decrease in CD4(+) T cells, typical for terminal SIV disease. Finally documented was the striking emergence of up to 19% of HTLV-associated "flower cell" lymphocytes in the circulation, as seen in patients with adult T cell leukemia/lymphoma. CD8(+)CD25(+) T cell subpopulation increases were positively correlated with flower cell appearance and suggested their possible role in this process. We conclude that SIV may have the potential to up-regulate HTLV-1 and disease expression.
SourceAvailable from: Mirdad Kazanji[Show abstract] [Hide abstract]
ABSTRACT: Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4+ and CD8+ T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4+ and CD8+ T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates.Virology 04/2014; s 454–455:184–196. DOI:10.1016/j.virol.2014.02.019 · 3.28 Impact Factor
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ABSTRACT: The infection dynamics and pathology of a retrovirus may be altered by one or more additional virus(es). To investigate this we characterised proviral load, biodistribution and the immune response in Macaca fascicularis naturally-infected with combinations of SRV-2 and STLV-I. Since the mesenteric lymph node (MLN) and the spleen have been previously implicated in response to retroviral infection, the morphology and immunopathology of these tissues were assessed. Our data revealed a significant change in SRV-2 biodistribution in macaques infected with STLV-I. Pathological changes were greater in the MLN and spleen of STLV-I infected and co-infected macaques, compared with the other groups. Immune cell populations in co-infected macaque spleens were increased and there was an atypical distribution of B-cells. These findings suggest that the infection dynamics of each virus in a co-infected individual may be affected to a different extent and that STLV-I appears to be responsible for enhancing the biodistribution and associated pathological changes of SRV-2 in macaques.Journal of General Virology 11/2012; DOI:10.1099/vir.0.046078-0 · 3.53 Impact Factor
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ABSTRACT: The non-structural proteins encoded by the orf-I, II, III, and IV genes of the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) genome, are critical for the modulation of cellular gene expression and T-cell proliferation, the escape from cytotoxic T-cells and natural killer cells, and virus expression. In here, we review the main functions of the HTLV-1 orf-I products. The 12kDa product from orf-I (p12) is proteolytically cleaved within the endoplasmic reticulum (ER) to generate the 8kDa protein (p8). At the steady state, both proteins are expressed at similar levels in transfected T-cells. The p12 protein remains in the ER and cis-Golgi, whereas the p8 protein traffics to the cell surface and is recruited to the immunological synapse. The p12 and the p8 proteins have seemingly opposite effects on T-cells; the ER resident p12, modulates T-cell activation and proliferation, whereas p8 induces T-cell anergy. The p8 protein also increases the formation of cellular conduits, is transferred to neighboring T-cells, and increases virus transmission. The requirement for HTLV-1 infectivity of orf-I is demonstrated by the loss of virus infectivity in macaques exposed to an engineered virus, whereby expression of orf-I was ablated. Altogether the current knowledge demonstrates that the concerted activity of p8 and p12 is essential for the persistence of virus infected cells in the host.Molecular Aspects of Medicine 10/2010; 31(5):333-43. DOI:10.1016/j.mam.2010.07.001 · 10.30 Impact Factor