Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
J Med Virol. 2019 Nov;91(11):1960-1969. doi: 10.1002/jmv.25548. Epub 2019 Jul 25.
Hepatitis E is an important global disease, causing outbreaks of acute hepatitis in many developing countries and sporadic cases in industrialized countries. Hepatitis E virus (HEV) infection typically causes self-limiting acute hepatitis but can also progress to chronic disease in immunocompromised individuals. The immune response necessary for the prevention of chronic infection is T cell-dependent; however, the arm of cellular immunity responsible for this protection is not currently known. To investigate the contribution of humoral immunity in control of HEV infection and prevention of chronicity, we experimentally infected 20 wild-type (WT) and 18 immunoglobulin knockout (JH-KO) chickens with a chicken strain of HEV (avian HEV). Four weeks postinfection (wpi) with avian HEV, JH-KO chickens were unable to elicit anti-HEV antibody but had statistically significantly lower liver lesion scores than the WT chickens. At 16 wpi, viral RNA in fecal material and liver, and severe liver lesions were undetectable in both groups. To determine the role of cytotoxic lymphocytes in the prevention of chronicity, we infected 20 WT and 20 cyclosporine and CD8 antibody-treated chickens with the same strain of avian HEV. The CD8 lymphocyte-depleted, HEV-infected chickens had higher incidences of prolonged fecal viral shedding and statistically significantly higher liver lesion scores than the untreated, HEV-infected birds at 16 wpi. The results indicate that CD8 lymphocytes are required for viral clearance and reduction of liver lesions in HEV infection while antibodies are not necessary for viral clearance but may contribute to the development of liver lesions in acute HEV infection.
戊型肝炎是一种重要的全球性疾病，在许多发展中国家引发急性肝炎暴发，在工业化国家也有散发病例。戊型肝炎病毒（HEV）感染通常导致自限性急性肝炎，但在免疫功能低下的个体中也可进展为慢性疾病。预防慢性感染所需的免疫反应依赖于 T 细胞；然而，目前尚不清楚负责这种保护的细胞免疫分支。为了研究体液免疫在控制 HEV 感染和预防慢性感染中的作用，我们用禽源 HEV 实验性感染了 20 只野生型（WT）和 18 只免疫球蛋白敲除（JH-KO）鸡。感染禽源 HEV 4 周后（感染后 4 周），JH-KO 鸡无法产生抗 HEV 抗体，但肝脏病变评分明显低于 WT 鸡。在 16 周时，粪便和肝脏中的病毒 RNA 以及严重的肝脏病变在两组中均无法检测到。为了确定细胞毒性淋巴细胞在预防慢性感染中的作用，我们用相同的禽源 HEV 感染了 20 只 WT 和 20 只环孢菌素和 CD8 抗体处理的鸡。在 16 周时，CD8 淋巴细胞耗竭、HEV 感染的鸡粪便中病毒持续脱落的发生率更高，肝脏病变评分明显高于未经处理、HEV 感染的鸟类。结果表明，在 HEV 感染中，CD8 淋巴细胞对于病毒清除和减少肝脏病变是必需的，而抗体对于病毒清除不是必需的，但可能有助于急性 HEV 感染中肝脏病变的发展。
