RESUMO
Human T cell lymphotropic virus types I and II (HTLV-I/II) are endemic in certain areas of the world. The cause two life-threatening diseases, adult T cell leukaemia/lymphoma and tropical spastic paraparesis. A vaccine is needed because in developing countries there are no other feasible preventive interventions against these diseases and in Western countries intravenous drug users at high risk for HTLV-I and HTLV-II infections and the health workers in contact with such populations must be protected. We have developed a rat model in which we observed variations of susceptibility to viral infection between inbred strains, the most susceptible being Fischer F344, and the possibility of viral latency in the nervous system. We have prepared a recombinant adenovirus vector that expresses the HTLV-I envelope glycoprotein env in HeLa cells. A target human population in French Guyana, in which the prevalence rate reaches 5.6 percent in one ethnic group (Bonis), has been identified for possible intervention (AU)
Assuntos
21003 , Humanos , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Infecções por HTLV-I/prevenção & controle , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Infecções por HTLV-II/prevenção & controle , Vacinas Sintéticas/uso terapêutico , Vacinas Virais/uso terapêutico , Modelos Animais de Doenças , Estudos de Viabilidade , Leucemia-Linfoma de Células T do Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras/prevenção & controle , Paraparesia Espástica Tropical/prevenção & controleRESUMO
Twelve long term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-I) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long term interlukin-2-dependent cell lines exhibited a pattern characteristic of CD4+ -activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50 percent of the cells exhibited HTLV-I antigens by IF. However numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high M-r polypeptides were detected by Western blot in cell lysates when comparing TSP-or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46. (AU)
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Antígenos HTLV-I/análise , Paraparesia Espástica Tropical/imunologia , Linfócitos T/imunologia , Antígenos CD/análise , Western Blotting , Divisão Celular , Linhagem Celular , Vírus Linfotrópico T Tipo 1 Humano/crescimento & desenvolvimento , Vírus Linfotrópico T Tipo 1 Humano/ultraestrutura , Microscopia Eletrônica , Fenótipo , Linfócitos T/microbiologia , Linfócitos T/ultraestrutura , Proteínas do Core Viral/análise , República Centro-Africana , Guiana Francesa , Índias Ocidentais , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica TropicalRESUMO
Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clincal illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one call, we estimated that this HTLV-I integration is present in 3 percent to 15 percent of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10 percent of thier lymphocytes abnormal, presening either a misshapen nucleus or an adult T-cell leukemia/lymphoma(ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity. (AU)
Assuntos
Humanos , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucócitos Mononucleares/microbiologia , Paraparesia Espástica Tropical/microbiologia , Anticorpos Monoclonais , Antígenos CD , Southern Blotting , Células Clonais , Sondas de DNA , DNA Viral/análise , Guiana Francesa , Anticorpos Antideltaretrovirus/análise , Côte d'Ivoire , Martinica , Mapeamento por Restrição , Proteínas do Envelope Viral/genética , Índias Ocidentais , República Democrática do CongoRESUMO
Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strenghten the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies. (AU)