CCR5 receptor antagonism inhibits hepatitis C virus (HCV) replication in vitro

Autoři: Jason T. Blackard aff001;  Ling Kong aff001;  Susan D. Rouster aff001;  Rebekah Karns aff002;  Paul S. Horn aff003;  Shyam Kottilil aff005;  M. Tarek Shata aff001;  Kenneth E. Sherman aff001
Působiště autorů: Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America aff001;  Digestive Health Center, Cincinnati Children’s Hospital, Cincinnati, OH, United States of America aff002;  Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America aff003;  Neurology Division, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States of America aff004;  University of Maryland, Baltimore, MD, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Background and aim

The hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV. We evaluated the effect of CCR5 blockade or knockdown on HCV replication in Huh7.5JFH1 cells.


Cells were exposed to varying concentrations of maraviroc (CCR5 inhibitor), cenicriviroc (CCR2/CCR5 inhibitor), sofosbuvir (nucleotide polymerase inhibitor), or raltegravir (HIV integrase inhibitor).


HCV RNA was detected utilizing two qualitative strand-specific RT-PCR assays. HCV core antigen and NS3 protein was quantified in the supernatant and cell lysate, respectively. siRNA was utilized to knockdown CCR5 gene expression in hepatocytes. Alternatively, anti-CCR5 antibodies were employed to block the receptor. Supernatant levels of HCV RNA (expressed as fold change) were not reduced in the presence of raltegravir but were reduced 8.55-fold and 12.42-fold with cenicriviroc and maraviroc, respectively. Sofosbuvir resulted in a 16.20-fold change in HCV RNA levels. HCV core and NS3 protein production was also reduced in a dose-dependent manner. Two distinct anti-CCR5 antibodies also resulted in a significant reduction in HCV protein expression, as did siRNA knockdown of CCR5 gene expression.


These data provide evidence that CCR5 modulation could have a significant effect on HCV replication in an in vitro system. Further evaluation of the role of CCR5 inhibition in clinical settings may be warranted.

Klíčová slova:

Hepatitis C virus – Hepatocytes – Chemokines – Small interfering RNAs – Viral replication – Virions – CCR5 coreceptor


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2019 Číslo 10
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