Virus-host immune interaction in asymptomatic HTLV-1 carriers.

UNLABELLED: Human T-cell leukemia virus type 1 (HTLV-1) induces chronic long-term latent infection that can cause fatal diseases, including adult T-cell leukemia. HTLV-1 production is poor and undetectable during the asymptomatic phase of infection. Virus-host immune interaction in latent infection has not been fully determined. In the present study, virus-specific antibody and T-cell responses in asymptomatic HTLV-1 carriers (n = 77) were investigated. Neutralizing antibody responses were significantly higher in individuals with higher anti-Env SU (gp46) antibody levels and positively correlated with proviral loads. Overnight ex vivo culture of peripheral blood mononuclear cells resulted in detectable HTLV-1 Gag antigen (p19) expression in CD4+ T cells and interferon-γ (IFN-γ) induction in CD8+ T cells. Frequencies of these p19-expressing CD4+ T cells and non-specific IFN-γ-induced CD8+ T cells were positively correlated with proviral loads, respectively. Tax-specific CD8+ T-cell frequencies were not associated with proviral loads but inversely correlated with the ratios of p19-expressing CD4+ T-cell frequencies to proviral loads, implying the involvement of Tax-specific CD8+ T cells in the control of HTLV-1 replication. These results provide insights into the elucidation of the virus-host immune interaction in latent HTLV-1 infection.

IMPORTANCE: Human T-cell leukemia virus type 1 (HTLV-1) can cause fatal diseases, including adult T-cell leukemia in humans after long-term asymptomatic infection. In asymptomatic HTLV-1 carriers, substantial proviruses are detectable in lymphocytes, and the association of a higher proviral load with a higher risk of disease progression has been observed. However, viral replication is controlled and HTLV-1 production is poor in asymptomatic carriers. Virus-host immune interaction during latent infection has not been fully determined. In the present study, virus-specific antibody and T-cell responses in asymptomatic HTLV-1 carriers were investigated. Neutralizing antibody responses were positively correlated with proviral loads. Tax-specific CD8+ T-cell frequencies were not associated with proviral loads but inversely correlated with the ratios of p19-expressing CD4+ T-cell frequencies to proviral loads, supporting the notion that Tax-specific CD8+ T-cell responses play an important role in the control of HTLV-1 replication. These results provide insights into the mechanism of virus-host immune interaction in latent HTLV-1 infection.