Low-level HIV infection of hepatocytes

Ling Kong,Kenneth E Sherman,Walter Cardona Maya,Maria E Moreno-Fernandez,Claire Chougnet,Jason T Blackard,Mohamed T Shata,Gang Ma

doi:10.1186/1743-422x-9-157

Abstract

BackgroundThere are only limited data on whether HIV infection occurs within the liver; therefore, we explored early and late stages of the HIV life cycle in two hepatocyte cell lines – Huh7.5 and Huh7.5JFH1 – as well as in primary human hepatocytes.ResultsIntegrated HIV DNA was detected in Huh7.5 and Huh7.5JFH1 cells, as well as in primary hepatocytes, and was inhibited by the integrase inhibitor raltegravir in a dose-dependent manner. HIV p24 protein was also detected in cell culture supernatants at days 1, 3, 5, and 7 post-infection and was inhibited by AZT, although levels were modest compared to those in a lymphocyte cell line. Culture supernatants from HIV-infected hepatocytes were capable of infecting a non-hepatic HIV indicator cell line.ConclusionsThese results indicating low-level HIV replication in hepatoctyes in vitro complement evidence suggesting that HIV has deleterious effects on the liver in vivo.

Highlights

There are only limited data on whether HIV infection occurs within the liver; we explored early and late stages of the HIV life cycle in two hepatocyte cell lines – Huh7.5 and Huh7.5JFH1 – as well as in primary human hepatocytes
Detection of integrated HIV DNA in hepatocytes To assess HIV infection of hepatocytes, we first examined whether the Huh7.5 and Huh7.5JFH1 cell lines could support early steps in the HIV life cycle
The Jurkat lymphocyte cell line was evaluated as a positive control, and demonstrated that HIV integration was approximately 10-fold higher in lymphocytes compared to hepatocytes (Figure 1D)

Summary

Introduction

There are only limited data on whether HIV infection occurs within the liver; we explored early and late stages of the HIV life cycle in two hepatocyte cell lines – Huh7.5 and Huh7.5JFH1 – as well as in primary human hepatocytes. Liver enzyme elevations are frequent in persons with HIV infection even in the absence of viral hepatitis [6,7]. In vivo data further demonstrate the presence of HIV RNA, proviral DNA, and viral proteins in several hepatic cell types, including hepatocytes (reviewed in [9]). Hepatitis C virus (HCV) – a major cause of chronic liver disease – is a significant public health threat worldwide with ~130 million infected persons [10]. Due to their shared routes of transmission, HIV/HCV coinfection is frequent, and liver disease is a major cause

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Conclusion