Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells

Linda Andrus, Svetlana Marukian, Christopher T. Jones, Maria Teresa Catanese, Timothy P. Sheahan, John W. Schoggins, Walter T. Barry, Lynn B. Dustin, Kartik Trehan, Alexander Ploss, Sangeeta N. Bhatia, Charles M. Rice

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Abstract

Here we demonstrate that primary cultures of human fetal liver cells (HFLC) reliably support infection with laboratory strains of hepatitis C virus (HCV), although levels of virus replication vary significantly between different donor cell preparations and frequently decline in a manner suggestive of active viral clearance. To investigate possible contributions of the interferon (IFN) system to control HCV infection in HFLC, we exploited the well-characterized ability of paramyxovirus (PMV) V proteins to counteract both IFN induction and antiviral signaling. The V proteins of measles virus (MV) and parainfluenza virus 5 (PIV5) were introduced into HFLC using lentiviral vectors encoding a fluorescent reporter for visualization of HCV-infected cells. V protein-transduced HFLC supported enhanced (10 to 100-fold) levels of HCV infection relative to untransduced or control vector-transduced HFLC. Infection was assessed by measurement of virus-driven luciferase, by assays for infectious HCV and viral RNA, and by direct visualization of HCV-infected hepatocytes. Live cell imaging between 48 and 119 hours postinfection demonstrated little or no spread of infection in the absence of PMV V protein expression. In contrast, V protein-transduced HFLC showed numerous HCV infection events. V protein expression efficiently antagonized the HCV-inhibitory effects of added IFNs in HFLC. In addition, induction of the type III IFN, IL29, following acute HCV infection was inhibited in V protein-transduced cultures. Conclusion: These studies suggest that the cellular IFN response plays a significant role in limiting the spread of HCV infection in primary hepatocyte cultures. Strategies aimed at dampening this response may be key to further development of robust HCV culture systems, enabling studies of virus pathogenicity and the mechanisms by which HCV spreads in its natural host cell population. (HEPATOLOGY 2011;)

Original languageEnglish (US)
Pages (from-to)1901-1912
Number of pages12
JournalHepatology
Volume54
Issue number6
DOIs
StatePublished - Dec 2011

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Hepacivirus
Liver
Virus Diseases
Interferons
Paramyxovirus V protein
Hepatocytes
Parainfluenza Virus 5
Proteins
Hepatovirus
Laboratory Infection
Viruses
Viral RNA
Virus Replication
Infection
Luciferases
Antiviral Agents
Virulence

ASJC Scopus subject areas

  • Hepatology

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Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells. / Andrus, Linda; Marukian, Svetlana; Jones, Christopher T.; Catanese, Maria Teresa; Sheahan, Timothy P.; Schoggins, John W.; Barry, Walter T.; Dustin, Lynn B.; Trehan, Kartik; Ploss, Alexander; Bhatia, Sangeeta N.; Rice, Charles M.

In: Hepatology, Vol. 54, No. 6, 12.2011, p. 1901-1912.

Research output: Contribution to journalArticle

Andrus, L, Marukian, S, Jones, CT, Catanese, MT, Sheahan, TP, Schoggins, JW, Barry, WT, Dustin, LB, Trehan, K, Ploss, A, Bhatia, SN & Rice, CM 2011, 'Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells', Hepatology, vol. 54, no. 6, pp. 1901-1912. https://doi.org/10.1002/hep.24557
Andrus, Linda ; Marukian, Svetlana ; Jones, Christopher T. ; Catanese, Maria Teresa ; Sheahan, Timothy P. ; Schoggins, John W. ; Barry, Walter T. ; Dustin, Lynn B. ; Trehan, Kartik ; Ploss, Alexander ; Bhatia, Sangeeta N. ; Rice, Charles M. / Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells. In: Hepatology. 2011 ; Vol. 54, No. 6. pp. 1901-1912.
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AU - Catanese, Maria Teresa

AU - Sheahan, Timothy P.

AU - Schoggins, John W.

AU - Barry, Walter T.

AU - Dustin, Lynn B.

AU - Trehan, Kartik

AU - Ploss, Alexander

AU - Bhatia, Sangeeta N.

AU - Rice, Charles M.

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