Infection of common marmosets with hepatitis C virus/GB virus-B chimeras

Li, Tingting; Zhu, Shaoyu; Shuai, Lifang; Xu, Yikai; Yin, Sha; Bian, Yixin; Wang, Yuanzhan; Zuo, Bingfeng; Wang, Wenjing; Zhao, Shuoxian; Zhang, Ling; Zhang, George; Gao, George F.; Allain, Jean‐Pierre; Li, Chengyao

doi:10.1002/hep.26750

Cited by 28 publications

(55 citation statements)

References 35 publications

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“…2), with viral replication patterns similar to those seen in HCV-infected patients and in previously reported HCV C-E1-E2-p7 or E1-E2-p7 chimera-infected marmosets (22,47). The viral loads in two FK506-treated immunosuppressed marmosets (M23-P 0 and M24-P 1 ) were significantly higher than those in immunocompetent animals (P ϭ 0.02).…”

Section: Discussionsupporting

confidence: 80%

“…Serum from M23-P 0 at wk 4, 5, 8 50 Control P 0 M2-P 0 PBS buffer 26 P 0 M4-P 0 GBV-B RNA 23 P 1 M9-P 1 GBV-B serum of M4-P 0 29 P 1 -FK506 as described previously (22). Viral cDNA was synthesized with random primers and sequenced commercially by next-generation sequencing (Huada Gene Company, Shenzhen, China).…”

mentioning

confidence: 99%

“…The formalin-fixed, paraffin-embedded liver tissues were tested for HCV NS2 to -4A protein expression by immunohistochemical (IHC) staining as described previously (22). Primary antibodies to HCV NS3 (clone 3E5) and to both HCV and GBV-B NS3 conserved epitopes (clone 2E12) were available in the laboratory (24).…”

mentioning

confidence: 99%

“…The liver tissues of marmosets were examined with hematoxylin and eosin (H&E) staining and Masson's trichrome staining as described previously (22). The necrosis and inflammation were graded on a scale of 0 to 18, while fibrosis was scored on a scale of 0 to 6 according to the modified HAI system (26,27).…”

mentioning

confidence: 99%

“…The peptides (4 g/ml each) were pooled in PBS. The specific T-cell response of peripheral blood mononuclear cells (PBMCs) from marmosets was measured by stimulating them with the pooled peptides in an enzyme-linked immunosorbent spot (ELISpot) assay as described previously (22). A precoated human gamma interferon (IFN-␥) ELISpot Plus plate (Mebtech AB, Sweden) was used in the assay.…”

mentioning

confidence: 99%

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Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus

Zhu

Liu

et al. 2016

J Virol

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A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. H epatitis C virus (HCV) infection is a global health threat thatcauses chronic hepatitis and is associated with 78% of primary hepatocellular carcinoma (1). Currently, limitations of small-primate models hamper the development of HCV vaccines and affordable antiviral drugs. Chimpanzees have been used as a uniquely reliable animal for HCV infection in past decades (2), significantly contributing to defining the infection natural history, pathogenesis, immune response, and rechallenge of HCV (3-6). However, the utility of chimpanzees has been more and more restricted by ethical concerns, and though rare, the use of this primate model in medical studies is extremely costly (2). The nonprimate animal models simulating HCV infection might potentially be mimicked with rodent hepacivirus (RHV)-infected rats (7,8), canine hepacivirus (CHV)-infected dogs (9), and equine hepacivirus (EHCV) (nonprimate hepacivirus [NPHV])-infected horses (10). HCV infection in immunocompetent mice was reported in genetically humanized mouse CD81 and occludin (OCLN) (11,12). However, the differences in infection courses and immune responses fundamentally separate these mice from HCV-infected patients.Common marmosets (Callithrix jacchus), one of the New World small ...

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus

Zhu

Liu

et al. 2016

J Virol

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Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

Dale

Hood

Bowen

et al. 2020

Journal of Medical Virology

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GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.

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Mouse Models for Studying HCV Vaccines and Therapeutic Antibodies

Gaska

Ding

Ploß

2018

Methods in Molecular Biology

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In spite of the immense progress in hepatitis C virus (HCV) research, efforts to prevent infection, such as generating a vaccine, have not yet been successful. The high price tag associated with current treatment options for chronic infection and the spike in new infections concurrent with growing opioid abuse are strong motivators for developing effective immunization and understanding neutralizing antibodies’ role in preventing infection. Humanized mice—both human liver chimeras as well as genetically humanized models—are important platforms for testing both possible vaccine candidates as well as antibody-based therapies. This chapter details the variety of ways humanized mouse technology can be employed in pursuit of learning how HCV infection can be prevented.

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Infection of common marmosets with hepatitis C virus/GB virus-B chimeras

Cited by 28 publications

References 35 publications

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

Mouse Models for Studying HCV Vaccines and Therapeutic Antibodies

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