Abstract
We used mandrills (Mandrillus sphinx) naturally infected with simian T-cell leukemia virus type 1 (STLV-1) as a model for evaluating the influence of natural STLV-1 infection on the dynamics and evolution of the immune system during chronic infection. Furthermore, in order to evaluate the role of the immune system in controlling the infection during latency, we induced immunosuppression in the infected monkeys. We first showed that the STLV-1 proviral load was higher in males than in females and increased significantly with the duration of infection: mandrills infected for 10–6 years had a significantly higher proviral load than those infected for 2–4 years. Curiously, this observation was associated with a clear reduction in CD4+ T-cell number with age. We also found that the percentage of CD4+ T cells co-expressing the activation marker HLA-DR and the mean percentage of CD25+ in CD4+ and CD8+ T cells were significantly higher in infected than in uninfected animals. Furthermore, the STLV-1 proviral load correlated positively with T-cell activation but not with the frequency of T cells secreting interferon γ in response to Tax peptides. Lastly, we showed that, during immunosuppression in infected monkeys, the percentages of CD8+ T cells expressing HLA-DR+ and of CD4+ T cells expressing the proliferation marker Ki67 decreased significantly, although the percentage of CD8+ T cells expressing HLA-DR+ and Ki67 increased significantly by the end of treatment. Interestingly, the proviral load increased significantly after immunosuppression in the monkey with the highest load. Our study demonstrates that mandrills naturally infected with STLV-1 could be a suitable model for studying the relations between host and virus. Further studies are needed to determine whether the different compartments of the immune response during infection induce the long latency by controlling viral replication over time. Such studies would provide important information for the development of immune-based therapeutic strategies.
Highlights
Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia/lymphoma (ATLL) [1] and of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/ HAM) [2], has been implicated in pediatric infectious dermatitis [3], uveitis [4], arthropathy [5] and polymyositis [6].Simian T cell leukemia virus (STLV–1), the simian counterpart of HTLV-1, naturally infects Old World monkeys and shares virologic, immunologic, molecular, and pathologic features with HTLV-1 [7,8,9]
The phylogenic relations of most known subtypes indicate that simian T-cell leukemia virus type 1 (STLV-1) is the simian ancestor of HTLV-1, the latter arising by transmission from multiple nonhuman primates to humans [10,11,12,13,14]
The possibility of crossspecies transmission of STLV-1 to humans is supported by the fact that the STLV infection in mandrills (STLVmnd) viruses so far characterized are genetically similar to HTLV-1 subtype D and F viruses isolated from people living in central Africa [11,19]
Summary
Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia/lymphoma (ATLL) [1] and of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/ HAM) [2], has been implicated in pediatric infectious dermatitis [3], uveitis [4], arthropathy [5] and polymyositis [6].Simian T cell leukemia virus (STLV–1), the simian counterpart of HTLV-1, naturally infects Old World monkeys and shares virologic, immunologic, molecular, and pathologic features with HTLV-1 [7,8,9]. The phylogenic relations of most known subtypes indicate that STLV-1 is the simian ancestor of HTLV-1, the latter arising by transmission from multiple nonhuman primates to humans [10,11,12,13,14]. African HTLV-1 and STLV-1 cannot be separated into distinct phylogenetic lineages on the basis of their species of origin, but rather on the geographic origin of their hosts. All this suggests that STLV infection of mandrills could serve as a model of human HTLV infection. To evaluate the role of the immune system in controlling STLV-1 infection, we induced immunosuppression in naturally infected mandrills and evaluated the dynamics of immunologic and virologic parameters during and after treatment
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