Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2

Chen, Chialin; Huang, Jeffrey Y.; Wang, Chun‐Hsiang; Tahara, Stanley M.; Zhou, Lin; Kondo, Yasuteru; Schechter, Joel; Su, Lishan; Lai, Michael M. C.; Wakita, Takaji; Cosset, François‐Loïc; Jung, Jae U.; Machida, Keigo

doi:10.1038/ncomms13882

Cited by 36 publications

(33 citation statements)

References 81 publications

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“…Similar to HPgV-2, HPgV can replicate in PBMCs, although it appears to be pan-lymphotropic and can infect multiple mononuclear cells including CD4 + T cells, CD8 + T cells, B cells, monocytes, and NK-cells [35,36]. Our results also show the infection and replication of HCV in B lymphocytes, which is consistent with earlier reports by Chen et al, who have determined the lymphotropism of HCV by using cellular protein B7.2 as co-receptor [37]. Wang et al reported that the association of HCV with B cells occurs mainly through the interaction of complement receptor 2 (CD21) and the CD19/CD81 complex [38].…”

Section: Discussionsupporting

confidence: 92%

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

Wan

Liu

et al. 2020

Emerging Microbes & Infections

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Tang (2020) Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication, Emerging Microbes & Infections, 9:1,[485][486][487][488][489][490][491][492][493][494][495] 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 coinfected 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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Section: Discussionsupporting

confidence: 92%

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

Wan

Liu

et al. 2020

Emerging Microbes & Infections

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“…HCV is not only a hepatotropic but also a lymphotropic virus, and this finding has been supported by the results of several reports that demonstrated the association of HCV with B cells both in vitro and in vivo. 11,20,21 Furthermore, our previous studies indicated that HCV 22 In this study, we confirmed that HCV RNA was detected in B cells of 83.3% and 50% of CH-C patients with G1 and G2, respectively, as previously described (Table 1). 11,14 This result suggested that HCV G1 was more lymphotropic than HCV G2;…”

Section: Discussionsupporting

confidence: 90%

Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study

Arai

Ito

Shimozuma

et al. 2020

Health Science Reports

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Aims Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV‐infected patients during antiviral therapy and investigated the effects of viral eradication. Methods One hundred and eighty‐one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy. Results HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non‐major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN‐based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN‐free therapy was started and remained low during the therapy. Conclusions These results suggested that IFN‐free therapy potentially eradicated HCV in the B cells, leading to the down‐regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.

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“…The recent finding that a co-stimulatory receptor B7.2 (CD86) is involved in the infection of human memory B cells by the abovementioned HCV SB strain [66] substantiated the involvement of a hepatocyte-distinct receptor in HCV lymphotropism [87] ( Table 1). The study showed that the virus E1E2 envelope and 5′-UTR sequences determine lymphotropism of the SB strain and that silencing of the virus sensor retinoic acid-inducible gene I (RIGI) or overexpression of micrcoRNA-122 permitted the persistence of viral replication in B cells.…”

Section: An Important Finding Toward the Recognition Of Virological Dmentioning

confidence: 79%

HCV Lymphotropism and Its Pathogenic Significance

Michalak¹

2018

Hepatitis C - From Infection to Cure

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Hepatitis C virus (HCV) is not only a hepatotropic but also a lymphotropic virus. Infection of the immune system appears to be a natural propensity of HCV and, as the accumulated data indicate, a common characteristic of both symptomatic and clinically silent but molecularly evident infection known as occult infection. The ability of HCV to infect cells of the immune system is consistent with a significantly greater prevalence of certain lymphoproliferative disorders in HCV-infected patients, such as mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma. This chapter recapitulates the approaches used to detect HCV and its replication within lymphoid cells, features of HCV compartmentalization in the lymphatic system and in different types of immune cells, and the cell culture models developed to study HCV lymphotropism. In addition, the characteristics of the molecules recently identified as those specifically mediating HCV entry leading to virus replication in B and T lymphocytes, which are distinct from those involved in virus entry to hepatocytes, are presented. Finally, the biological impact of HCV lymphotropism on the function of immune cells, virus persistence, and immune cell proliferation and lymphomagenesis is summarized.

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Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2

Cited by 36 publications

References 81 publications

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

Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study

HCV Lymphotropism and Its Pathogenic Significance

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