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

ABSTRACTThe 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 longitudin...

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Main Authors: Zhengwei Wan, Junwei Liu, Fengyu Hu, Jingwei Shui, Linghua Li, Haiying Wang, Xiaoping Tang, Chengguang Hu, Yuanhao Liang, Yuanping Zhou, Weiping Cai, Shixing Tang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1730247
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author Zhengwei Wan
Junwei Liu
Fengyu Hu
Jingwei Shui
Linghua Li
Haiying Wang
Xiaoping Tang
Chengguang Hu
Yuanhao Liang
Yuanping Zhou
Weiping Cai
Shixing Tang
author_facet Zhengwei Wan
Junwei Liu
Fengyu Hu
Jingwei Shui
Linghua Li
Haiying Wang
Xiaoping Tang
Chengguang Hu
Yuanhao Liang
Yuanping Zhou
Weiping Cai
Shixing Tang
author_sort Zhengwei Wan
collection DOAJ
description ABSTRACTThe 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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spelling doaj.art-ac8a13771648486baab3b4596cb352602024-03-11T16:04:25ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019148549510.1080/22221751.2020.1730247Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replicationZhengwei Wan0Junwei Liu1Fengyu Hu2Jingwei Shui3Linghua Li4Haiying Wang5Xiaoping Tang6Chengguang Hu7Yuanhao Liang8Yuanping Zhou9Weiping Cai10Shixing Tang11Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of ChinaDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of ChinaDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of ChinaABSTRACTThe 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.https://www.tandfonline.com/doi/10.1080/22221751.2020.1730247HPgV-2persistent infectionresolved infectionlymphotropicHCV
spellingShingle Zhengwei Wan
Junwei Liu
Fengyu Hu
Jingwei Shui
Linghua Li
Haiying Wang
Xiaoping Tang
Chengguang Hu
Yuanhao Liang
Yuanping Zhou
Weiping Cai
Shixing Tang
Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
Emerging Microbes and Infections
HPgV-2
persistent infection
resolved infection
lymphotropic
HCV
title Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
title_full Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
title_fullStr Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
title_full_unstemmed Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
title_short Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication
title_sort evidence that the second human pegivirus hpgv 2 is primarily a lymphotropic virus and can replicate independent of hcv replication
topic HPgV-2
persistent infection
resolved infection
lymphotropic
HCV
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1730247
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