Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV- I- infected subjects using standard peptide screening methods

Autor(es)

Jones, R. ; Leal, Fabio ; Hasenkrug, Aaron ; Segurado, Aluisio ; Nixon, Douglas ; Ostrowski, Mario ; Kallas, Esper

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEGATIVE RESULTS IN BIOMEDICINE; v. 12, p. 6-pg., 2013-01-01.

Resumo

Background: An estimated 10-20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results: Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions: Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology. (AU)

• Processo FAPESP: 10/05845-0 - Resposta imune celular em doenças infecciosas e imunodeficiências primárias
• Beneficiário: Esper Georges Kallás
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
• Processo FAPESP: 04/15856-9 - Análise prospectiva das características virológicas e imunológicas em indivíduos com infecção recente pelo HIV-1 das cidades de São Paulo e Santos, SP
• Beneficiário: Ricardo Sobhie Diaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático