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Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication.
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2020-02-26 , DOI: 10.1080/22221751.2020.1730247
Zhengwei Wan 1 , Junwei Liu 2 , Fengyu Hu 3 , Jingwei Shui 1 , Linghua Li 3 , Haiying Wang 1 , Xiaoping Tang 3 , Chengguang Hu 2 , Yuanhao Liang 1 , Yuanping Zhou 2 , Weiping Cai 3 , Shixing Tang 1, 4
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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.

中文翻译:

有证据表明第二种人类佩吉病毒(HPgV-2)主要是淋巴病毒,可以独立于HCV复制而复制。

第二种人类佩吉病毒HPgV-2是一种新型的血源性病毒,与丙型肝炎病毒(HCV)感染密切相关。然而,有关其结合以及HPgV-2的自然史和组织嗜性的分子证据仍有待阐明。在这项纵向研究中,共纳入753名患者,其中包括512名HIV-1和HCV合并感染的患者,以表征HPgV-2感染的自然史。使用HPgV-2抗原的免疫组织化学染色和HPgV-2 RNA的原位杂交,收集外周血单个核细胞(PBMC)和肝脏活检样本,以确定HPgV-2的组织嗜性。我们记录了持续存在的HPgV-2感染(存在HPgV-2病毒RNA)和长达4.6年的抗体,并解决了HPgV-2感染,同时出现抗HPgV-2抗体下降和HPgV-2病毒血症清除的情况。此外,我们观察到通过直接作用抗病毒药(DAA)治疗可清除HCV,但未清除HPgV-2。生化测试和病理分析未发现任何由HPgV-2引起的肝功能损害的迹象。在肝活检样本中的淋巴细胞中检测到HPgV-2 RNA和非结构性抗原,但未检测到。另外,在PBMC中,特别是在B细胞中,检测到正链和负链HPgV-2 RNA。本研究是第一个提供证据证明HPgV-2是淋巴病毒,而不是肝病毒,并且HPgV-2复制与HCV病毒血症无关。这些新发现使我们对人类RNA病毒的进化和持续感染有了更深入的了解。
更新日期:2020-02-26
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