Van Epps H L, Schmaljohn C S, Ennis F A
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
J Virol. 1999 Jul;73(7):5301-8. doi: 10.1128/JVI.73.7.5301-5308.1999.
Hantaan virus, the prototypic member of the Hantavirus genus, causes hemorrhagic fever with renal syndrome in humans. We examined the human memory T-lymphocyte responses of three donors who had previous laboratory-acquired infections with Hantaan virus. We demonstrated virus-specific responses in bulk cultures of peripheral blood mononuclear cells (PBMC) from all donors. Bulk T-cell responses were directed against either Hantaan virus nucleocapsid (N) or G1 protein, and these responses varied between donors. We established both CD4(+) and CD8(+) N-specific cell lines from two donors and CD4(+) G1-specific cell lines from a third donor. All CD8(+) cytotoxic T-lymphocyte (CTL) lines recognized one of two epitopes on the nucleocapsid protein: one epitope spanning amino acids 12 to 20 and the other spanning amino acids 421 to 429. The CTL lines specific for amino acids 12 to 20 were restricted by HLA B51, and those specific for amino acids 421 to 429 were restricted by HLA A1. The N-specific CTL lines isolated from these two donors included both Hantaan virus-specific CTLs and hantavirus cross-reactive CTLs. Responses to both epitopes are detectable in short-term bulk cultures of PBMC from one donor, and precursor frequency analysis confirms that CTLs specific for these epitopes are present at relatively high precursor frequencies in the peripheral T-cell pool. These data suggest that infection with Hantaan virus results in the generation of CTL to limited epitopes on the nucleocapsid protein and that infection also results in the generation of cross-reactive T-cell responses to distantly related hantaviruses which cause the distinct hantavirus pulmonary syndrome. This is the first demonstration of human T-lymphocyte responses to Hantaan virus.
汉坦病毒是汉坦病毒属的原型成员，可引起人类肾综合征出血热。我们检测了三名曾有过实验室获得性汉坦病毒感染的供者的人类记忆性T淋巴细胞反应。我们在所有供者的外周血单核细胞（PBMC）大量培养物中证实了病毒特异性反应。大量T细胞反应针对汉坦病毒核衣壳（N）或G1蛋白，且这些反应在供者之间有所不同。我们从两名供者建立了CD4(+)和CD8(+) N特异性细胞系，从第三名供者建立了CD4(+) G1特异性细胞系。所有CD8(+)细胞毒性T淋巴细胞（CTL）系识别核衣壳蛋白上的两个表位之一：一个表位跨越氨基酸12至20，另一个跨越氨基酸421至429。针对氨基酸12至20的CTL系受HLA B51限制，针对氨基酸421至429的CTL系受HLA A1限制。从这两名供者分离出的N特异性CTL系包括汉坦病毒特异性CTL和汉坦病毒交叉反应性CTL。在一名供者的PBMC短期大量培养物中可检测到对两个表位的反应，前体频率分析证实针对这些表位的CTL在外周T细胞库中以相对较高的前体频率存在。这些数据表明，汉坦病毒感染导致针对核衣壳蛋白上有限表位产生CTL，且感染还导致对引起不同汉坦病毒肺综合征的远缘相关汉坦病毒产生交叉反应性T细胞反应。这是首次证明人类T淋巴细胞对汉坦病毒的反应。
