RESUMO
The progression of AIDS depends on the complex host and virus interactions. The most important disease progression hallmarks are immune activation and apoptosis. In this study, we address the prevalence of polymorphisms related to proinflammatory and apoptotic genes, such as IFNG (+874T/A), TNF (308G/A), IL6 (-174G/C), IL8 (-251A/T), FAS (-670A/G), and FASL (-124A/G) in 160 ethnically mixed HIV-1-infected patients from multicentre cohorts with different clinical outcomes (13 elite controllers [EC], 66 slow long-term non-progressors [LTNPs], and 81 progressors [P]). The genotyping was accomplished by TaqMan-qPCR. Among all the polymorphisms analyzed in the cytokines, the IL6 -174G/C polymorphism showed a higher frequency of GG genotype in the LTNP and LTNP+EC groups as compared to the P group. Moreover, there was a significantly higher frequency of the G allele in the LTNP and LTNP+EC groups as compared to the P group. On the other hand, the levels of CD4+ T lymphocytes were higher among individuals showing the AA and AG genotypes for the FASL -124A/G polymorphism as compared to the GG genotype. Furthermore, the AG and AA genotypes were more frequent, as compared to the GG genotype, in individuals showing a lower viral load. In contrast, for the FAS -670A/G polymorphism, a significantly higher viral load was observed in individuals with the AG genotype as compared to the GG genotype. In conclusion, we found three genetic allelic variants of the IL6 -174G/C, FASL -124A/G, and FAS -670A/G polymorphisms that were related to disease progression and immunological and virological markers in cohorts of HIV-1-positive ethnically mixed patients.
Assuntos
Proteína Ligante Fas/genética , Soropositividade para HIV/genética , Soropositividade para HIV/imunologia , Interleucina-6/genética , Receptor fas/genética , Adulto , Progressão da Doença , Etnicidade , Proteína Ligante Fas/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Soropositividade para HIV/etnologia , HIV-1/genética , HIV-1/imunologia , Humanos , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Receptor fas/imunologiaRESUMO
Arawete and Asurini Indian tribes were revisited after a 36-year follow-up in search of HTLV infections. 46 persons (23 from each tribe) were tested for HTLV-1/2 antibodies and viral DNA. None were positive; this was probably because of their social/cultural isolation from neighboring tribes where HTLV-2c is hyperendemic.
Assuntos
Infecções por Deltaretrovirus/etnologia , Infecções por Deltaretrovirus/transmissão , Povos Indígenas , Isolamento Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Criança , Pré-Escolar , DNA Viral/isolamento & purificação , Infecções por Deltaretrovirus/epidemiologia , Feminino , Seguimentos , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
HTLV-1 infections are persistent and frequently latent; however, productive infections trigger different types of immunological responses that utilize cytokines to control infection. The present study investigated the role of IFNG +874A/T polymorphisms among 153 HTLV-1-infected individuals (33 clinically diagnosed with TSP/HAM, 22 with rheumatologic manifestations, 2 with dermatitis, 1 with uveitis, and 95 asymptomatic patients) and 300 healthy control individuals. Genotyping and proviral HTLV-1 load assessment were performed using real-time PCR assays, and the plasma levels of IFN-γ were measured using an enzyme immunoassay (ELISA). Genotype frequencies were not significantly different, but the presence of the T allele was higher (p < 0.0142) among the asymptomatic patients. Plasma levels of IFN-γ were significantly higher (p < 0.0137) among those with the TT genotype. Their proviral load was also higher, although this elevation did not reach statistical significance. There was no difference in the IFN-γ plasma levels among the symptomatic patients, even when ranked according to disease severity (TSP/HAM or rheumatologic manifestations). However, the difference among asymptomatic patients with the T allele was significantly higher (p < 0.0016) and similar to the plasma levels observed among symptomatic individuals. These results suggest that the IFNG +874A/T polymorphism may modulate the plasma levels of IFN-γ during HTLV-1 infection. Asymptomatic carriers of the polymorphic genotypes appear to develop an inflammatory response in a shorter timeframe, triggering progression to HTLV-1-related symptoms and disorders. These results further suggest that HTLV-1-infected asymptomatic individuals expressing the IFNG +874A/T polymorphism should be monitored more closely in order to readily detect the increase in clinical symptoms, as these patients are potentially at risk of a poor prognosis and should therefore start available treatment procedures earlier.
RESUMO
Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with ATL and inflammatory diseases but remains a neglected health problem. HTLV-1 associated diseases were originally described as sporadic entities, but family aggregations have been reported. Viral, genetic, immunological and behavioral factors were used to explain family clusters, but until now a clear explanation remains uncertain. In the present study we report, for the first time, a family cluster of diseased persons presenting the infection across three generations associated with FAS -670A/G polymorphism.