Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
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有证据表明第二种人类 Pegivirus (HPgV-2) 主要是嗜淋巴细胞病毒并且可以独立于 HCV 复制进行复制

DOI:
10.1080/22221751.2020.1730247
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发表时间:
2020-01
影响因子:
13.2
通讯作者:
Shixing Tang
Shixing Tang
中科院分区:
医学2区
文献类型:
--
作者:
Zhengwei Wan;Junwei Liu;Fengyu Hu;Jingwei Shui;Linghua Li;Haiying Wang;Xiaoping Tang;Chengguang Hu;Yuanhao Liu;Yuanping Zhou;Weiping Cai;Shixing Tang

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摘要第二种人类巨细胞病毒HPgV-2是一种新的血液传播病毒,与丙型肝炎病毒(HCV)感染密切相关。然而,它们相互关联的分子证据以及HPgV-2的自然病史和组织趋向性仍有待阐明。在这项纵向研究中,共有753名患者入选,其中包括512名HIV-1和丙型肝炎病毒混合感染的患者,以描述HPgV-2感染的自然病史。采集外周血单个核细胞(PBMC)和肝活检组织标本,用HPgV-2抗原免疫组织化学染色和HPgV-2RNA原位杂交检测HPgV-2的组织趋向性。我们记录了持续存在HPgV-2病毒RNA和抗体长达4.6年的HPgV-2感染,并治愈了HPgV-2感染,同时伴随着抗HPgV-2抗体的下降和HPgV-2病毒血症的清除。此外,我们观察了直接作用抗病毒药物(DAAs)对丙型肝炎病毒的清除,但没有观察到HPgV-2的清除。生化测试和病理分析没有发现任何HPgV-2引起肝脏损害的迹象。HPgV-2RNA和非结构抗原在淋巴细胞中检测到,而在肝活检标本中的肝细胞中未检测到。此外,在PBMC中也检测到HPgV-2正链和负链RNA,尤其是在B细胞中。本研究首次证明HPgV-2是嗜淋巴病毒,而不是嗜肝病毒,并且HPgV-2复制与丙型肝炎病毒血症无关。这些新发现让我们对人类RNA病毒的进化和持续感染有了更深入的了解。
ABSTRACT The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.
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