High frequency of viral protein expression in human T cell lymphotropic virus type 1-infected peripheral blood mononuclear cells

Abstract

Most human T cell lymphotropic virus type (HTLV)-1-infected individuals mount a strong and persistently activated cytotoxic T lymphocyte (CTL) response to the virus, which implies that there is abundant chronic transcription of HTLV-1 genes. On the other hand, several observations suggest that HTLV-1 might be latent in vivo and therefore not detectable by CTLs. To clarify these discrepancies, we quantified the frequency of provirus-positive peripheral blood mononuclear cells (PBMCs) that were capable of expressing the HTLV-1 Tax protein, which is known to be the immunodominant target antigen recognized by HTLV-1-specific CTLs. The analysis showed that a significant proportion of HTLV-1-infected cells (from 14 to 100%) starts to express the Tax protein within a few hours of culture ex vivo. Phenotypic analysis confirmed that the main cell subpopulation expressing the Tax protein is CD4 positive. Frequent Tax expression in CD4(+) T lymphocytes in vivo might account for the chronic activation of the cytotoxic immune response observed in the majority of HTLV-1-infected patients and might contribute to the pathogenesis of HTLV-1-associated diseases.