STLV-1 as a model for studying HTLV-1 infection.

Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.

Simian T-lymphotropic Virus-associated lymphoma in 2 naturally infected baboons: T-cell clonal expansion and immune response during tumor development.

Two young female baboons naturally infected with simian T-lymphotropic virus type 1 (STLV1) were euthanized due to chronic respiratory disease that was unresponsive to treatment. Massive lymphocytic infiltration of the lung interstitium suggested a diagnosis of STLV-associated lymphoma. In each case, the diagnosis was confirmed through inverse PCR (IPCR) that detected monoclonally integrated STLV1 provirus in cellular DNA extracted from lymphoma tissue and peripheral blood cells (PBC). One dominant STLV1-infected T-cell clone and 3 minor clones were detected in PBC from each baboon. Using archived PBC DNA and primers within the proviral genome and chromosomal DNA flanking the STLV1 integration sites in PCR analyses, we determined that the dominant clone in one baboon had first appeared approximately 8 mo after infection and had circulated for 4 y before clinical disease developed. ELISA testing of archived serum revealed that both baboons seroconverted to the p19 and p24 gag proteins and the envelope gp46 protein but not to the viral tax protein. Titers to p24 and gp46 rose significantly after infection and remained relatively constant until death, whereas titers to p19 increased with time. Although spontaneous STLV1-associated lymphomas have been described in baboons, the STLV1-associated lymphomas described here occurred in 2 relatively young baboons, both of whom had become infected with STLV at 3 to 4 y of age and developed lymphoma within 5 y of infection.

Two distinct STLV-1 subtypes infecting Mandrillus sphinx follow the geographic distribution of their hosts.

The mandrill (Mandrillus sphinx) has been shown to be infected with an STLV-1 closely related to HTLV-1. Two distinct STLV-1 subtypes (D and F) infect wild mandrills with high overall prevalence (27.0%) but are different with respect to their phylogenetic relationship and parallel to the mandrills' geographic range. The clustering of these new STLV-1mnd sequences with HTLV-1 subtype D and F suggests first, past simian-to-human transmissions in Central Africa and second, that species barriers are easier to cross over than geographic barriers.

High variety of different simian T-cell leukemia virus type 1 strains in chimpanzees (Pan troglodytes verus) of the Taï National Park, Côte d'Ivoire.

We found human T-cell leukemia virus type 1- and simian T-cell leukemia virus type 1 (STLV-1)-related infections in 5 of 10 chimpanzees originating from three groups of wild chimpanzees. The new virus isolates showed a surprising heterogeneity not only in comparison to STLV-1 described previously in other primate species but also between the different chimpanzee groups, within a group, or even between strains isolated from an individual animal. The interdisciplinary combination of virology, molecular epidemiology, and long-term behavioral studies suggests that the primary route of infection might be interspecies transmission from other primates, such as red colobus monkeys, that are hunted and consumed by chimpanzees.

Simian T cell leukemia virus type I-induced malignant adult T cell leukemia-like disease in a naturally infected African green monkey: implication of CD8+ T cell leukemia.

Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV-I). The hematological features and the evidence for monoclonal integration of provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like disease. The expression of surface markers on the leukemic cells indicated that they were defined as an activated CD8+ T cell subset. Together with the finding that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with human ATL. Finally, we assessed characteristics of the CD8 chains on these transformed cells. The result indicated that the leukemic cells expressed only the alpha chains but not the beta chains. However, in the case of in vitro-transformed cell lines the expression pattern of the CD8 chains varied in individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both alphaalpha+ and alphabeta+) T cells in AGMs.

Spontaneously generated non-Hodgkin's lymphoma in twenty-seven simian T-cell leukemia virus type 1 antibody-positive baboons (Papio species).

Simian T-cell leukemia virus type 1 (STLV-1), a type C retrovirus associated with leukemia/lymphoma in Old World monkeys, is closely related to human T-cell leukemia virus type 1, the etiologic agent of adult T-cell leukemia/lymphoma in humans. In a colony of 3200 baboons, the prevalence of antibodies to STLV-1 is more than 40%. Seropositivity is more frequent in female baboons than in males and increases with age. Of 27 STLV-1 antibody-positive baboons with non-Hodgkin's lymphoma, 20 were females and 7 were males, ranging in age from 3 to 21 years (mean, 13 years). Non-Hodgkin's lymphoma was not found in STLV-1 antibody-negative baboons. Clinical signs and laboratory findings were variable but generally included lethargy, low body weights, anemia, dyspnea, lymphadenopathy, hepatosplenomegaly, pneumonia, nodular skin lesions, and leukemia with or without multilobulated lymphocytes in peripheral blood. Radiography revealed pulmonary infiltrates consistent with pneumonia in 17 of the baboons. Serum chemical values were normal except for hypercalcemia in one baboon. Lymphocytosis was found in 18 of the baboons, with leukemia diagnosed in 11. At necropsy, variable enlargement of lymph nodes and other lymphopoietic tissue was usually found. Pale tan to white space-occupying foci typical of proliferative lymphoid tissue were often found in various organs, including lungs, spleens, livers, skin, and hearts. The lungs in 14 baboons had thickened pleuras, congestion,edema, and large tan to brown areas of consolidation.(ABSTRACT TRUNCATED AT 250 WORDS)