Fibrogenic Gene Expression in Hepatic Stellate Cells Induced by HCV and HIV Replication in a Three Cell Co-Culture Model System

Abdellah Akil, Mark Endsley, Saravanabalaji Shanmugam, Omar Saldarriaga, Anoma Somasunderam, Heidi Spratt, Heather Stevenson-Lerner, Netanya S. Utay, Monique Ferguson, Min Kyung Yi

Research output: Contribution to journalArticle

Abstract

Retrospective studies indicate that co-infection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) accelerates hepatic fibrosis progression. We have developed a co-culture system (MLH) comprising primary macrophages, hepatic stellate cells (HSC, LX-2), and hepatocytes (Huh-7), permissive for active replication of HCV and HIV, and assessed the effect of these viral infections on the phenotypic changes and fibrogenic gene expression in LX-2 cells. We detected distinct morphological changes in LX-2 cells within 24 hr post-infection with HCV, HIV or HCV/HIV in MLH co-cultures, with migration enhancement phenotypes. Human fibrosis microarrays conducted using LX-2 cell RNA derived from MLH co-culture conditions, with or without HCV and HIV infection, revealed novel insights regarding the roles of these viral infections on fibrogenic gene expression in LX-2 cells. We found that HIV mono-infection in MLH co-culture had no impact on fibrogenic gene expression in LX-2 cells. HCV infection of MLH co-culture resulted in upregulation (>1.9x) of five fibrogenic genes including CCL2, IL1A, IL1B, IL13RA2 and MMP1. These genes were upregulated by HCV/HIV co-infection but in a greater magnitude. Conclusion: Our results indicate that HIV-infected macrophages accelerate hepatic fibrosis during HCV/HIV co-infection by amplifying the expression of HCV-dependent fibrogenic genes in HSC.

Original languageEnglish (US)
Article number568
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Hepatic Stellate Cells
Virus Replication
Coculture Techniques
Hepacivirus
Virus Diseases
Cell Culture Techniques
HIV
Gene Expression
Coinfection
Fibrosis
Macrophages
Genes
Liver
Hepatocytes
Up-Regulation
Retrospective Studies
RNA
Phenotype

ASJC Scopus subject areas

  • General

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Fibrogenic Gene Expression in Hepatic Stellate Cells Induced by HCV and HIV Replication in a Three Cell Co-Culture Model System. / Akil, Abdellah; Endsley, Mark; Shanmugam, Saravanabalaji; Saldarriaga, Omar; Somasunderam, Anoma; Spratt, Heidi; Stevenson-Lerner, Heather; Utay, Netanya S.; Ferguson, Monique; Yi, Min Kyung.

In: Scientific Reports, Vol. 9, No. 1, 568, 01.12.2019.

Research output: Contribution to journalArticle

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