Asigbee Theodore Worlanyo, Nakamura-Hoshi Midori, Kuse Nozomi, Ishii Hiroshi, Ishikawa Koichi, Kawana-Tachikawa Ai, Horibe Erika, Nakashima Makoto, Yamano Yoshihisa, Uchimaru Kaoru, Matano Tetsuro
Graduate School of Medical Sciences and Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Microbiol Spectr. 2025 Mar 4;13(3):e0250724. doi: 10.1128/spectrum.02507-24. Epub 2025 Jan 31.
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 ( = 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 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.
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.
1型人类T细胞白血病病毒（HTLV-1）可引发慢性长期潜伏感染，进而导致包括成人T细胞白血病在内的致命疾病。在感染的无症状阶段，HTLV-1的产生很少且无法检测到。潜伏感染中病毒与宿主的免疫相互作用尚未完全明确。在本研究中，对无症状HTLV-1携带者（n = 77）的病毒特异性抗体和T细胞反应进行了调查。中和抗体反应在抗Env SU（gp46）抗体水平较高的个体中显著更高，且与前病毒载量呈正相关。外周血单个核细胞过夜培养导致在CD4 T细胞中可检测到HTLV-1 Gag抗原（p19）表达，在CD8 T细胞中诱导产生干扰素-γ（IFN-γ）。这些表达p19的CD4 T细胞和非特异性IFN-γ诱导的CD8 T细胞的频率分别与前病毒载量呈正相关。Tax特异性CD8 T细胞频率与前病毒载量无关，但与表达p19的CD4 T细胞频率与前病毒载量的比值呈负相关，这意味着Tax特异性CD8 T细胞参与了HTLV-1复制的控制。这些结果为阐明潜伏性HTLV-1感染中病毒与宿主的免疫相互作用提供了见解。
1型人类T细胞白血病病毒（HTLV-1）在长期无症状感染后可导致人类的致命疾病，包括成人T细胞白血病。在无症状HTLV-1携带者中，可在淋巴细胞中检测到大量前病毒，并且已观察到较高的前病毒载量与更高的疾病进展风险相关。然而，在无症状携带者中病毒复制受到控制且HTLV-1产生很少。潜伏感染期间病毒与宿主的免疫相互作用尚未完全明确。在本研究中，对无症状HTLV-1携带者的病毒特异性抗体和T细胞反应进行了调查。中和抗体反应与前病毒载量呈正相关。Tax特异性CD8 T细胞频率与前病毒载量无关，但与表达p19的CD4 T细胞频率与前病毒载量的比值呈负相关，支持了Tax特异性CD8 T细胞反应在控制HTLV-1复制中起重要作用的观点。这些结果为潜伏性HTLV-1感染中病毒与宿主免疫相互作用的机制提供了见解。
