scholarly journals Unexpected host range of hepatitis C virus replicons

Hepatology ◽  
2004 ◽  
Vol 39 (3) ◽  
pp. 835-838 ◽  
Author(s):  
Ralf Bartenschlager
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Range

scholarly journals Mice Expressing Minimally Humanized CD81 and Occludin Genes Support Hepatitis C Virus Uptake In Vivo

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Qiang Ding ◽  
Markus von Schaewen ◽  
Gabriela Hrebikova ◽  
Brigitte Heller ◽  
Lisa Sandmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Range ◽  
Amino Acid Sequences ◽  
Host Factors ◽  
Narrow Host Range ◽  
Junction Protein ◽  
Mouse Hepatocytes

ABSTRACT Hepatitis C virus (HCV) causes chronic infections in at least 150 million individuals worldwide. HCV has a narrow host range and robustly infects only humans and chimpanzees. The underlying mechanisms for this narrow host range are incompletely understood. At the level of entry, differences in the amino acid sequences between the human and mouse orthologues of two essential host factors, the tetraspanin CD81 and the tight junction protein occludin (OCLN), explain, at least in part, HCV's limited ability to enter mouse hepatocytes. We have previously shown that adenoviral or transgenic overexpression of human CD81 and OCLN facilitates HCV uptake into mouse hepatocytes in vitro and in vivo. In efforts to refine these models, we constructed knock-in mice in which the second extracellular loops of CD81 and OCLN were replaced with the respective human sequences, which contain the determinants that are critical for HCV uptake. We demonstrate that the humanized CD81 and OCLN were expressed at physiological levels in a tissue-appropriate fashion. Mice bearing the humanized alleles formed normal tight junctions and did not exhibit any immunologic abnormalities, indicating that interactions with their physiological ligands were intact. HCV entry factor knock-in mice take up HCV with an efficiency similar to that in mice expressing HCV entry factors transgenically or adenovirally, demonstrating the utility of this model for studying HCV infection in vivo. IMPORTANCE At least 150 million individuals are chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can result in progressive liver disease and liver cancer. New antiviral treatments can cure HCV in the majority of patients, but a vaccine remains elusive. To gain a better understanding of the processes culminating in liver failure and cancer and to prioritize vaccine candidates more efficiently, small-animal models are needed. Here, we describe the characterization of a new mouse model in which the parts of two host factors that are essential for HCV uptake, CD81 and occludin (OCLN), which differ between mice and humans, were humanized. We demonstrate that such minimally humanized mice develop normally, express the modified genes at physiological levels, and support HCV uptake. This model is of considerable utility for studying viral entry in the three-dimensional context of the liver and to test approaches aimed at preventing HCV entry.

scholarly journals Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus

Hepatology ◽  
2005 ◽  
Vol 41 (2) ◽  
pp. 265-274 ◽  
Author(s):  
Dimitri Lavillette ◽  
Alexander W. Tarr ◽  
C�cile Voisset ◽  
Peggy Donot ◽  
Birke Bartosch ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Range ◽  
Cell Entry

Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees

2001 ◽  
Vol 65 (4) ◽  
pp. 694-697 ◽  
Author(s):  
Jens Bukh ◽  
Carl L. Apgar ◽  
Sugantha Govindarajan ◽  
Robert H. Purcell
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Range ◽  
New World ◽  
New World Monkeys

HEPATITIS C VIRUS INFECTION (AND ADDITIONAL NEOPLASMS) AMONG MARGINAL ZONE LYMPHOMAS

1997 ◽  
Vol 96 (2) ◽  
pp. 427-428 ◽  
Author(s):  
FREDERICO SILVESTRI ◽  
GIOVANNI BARILLARI ◽  
RENATO FANIN ◽  
FLAVIA SALMASO ◽  
LAURA INFANTI ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Marginal Zone ◽  
Hepatitis C Virus Infection

Public health challenges in hepatitis C virus infection

2000 ◽  
Vol 15 (5 (Suppl.)) ◽  
pp. E83-E90 ◽  
Author(s):  
John M Kaldor ◽  
Gregory J Dore ◽  
Patricia Kl Correll
Keyword(s):  
Public Health ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Hepatitis C Virus Infection ◽  
Public Health Challenges
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