Low-level HIV infection of hepatocytes

Kong, Ling; Maya, Wálter Cardona; Moreno‐Fernandez, Maria E.; Ma, Gang; Shata, Mohamed T.; Sherman, Kenneth E.; Chougnet, Claire; Blackard, Jason T.

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

Cited by 47 publications

(43 citation statements)

References 50 publications

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“…Kong et al have reported detection of integrated HIV-1 DNA and release of infectious virus in liver epithelium following in vitro infection of hepatocyte cell lines and primary hepatocytes [102]. In addition, hepatic stellate cells have also been shown to release infectious virus following infection in vitro [103].…”

Section: Usual and Unusual Suspectsmentioning

confidence: 99%

Are T cells the only HIV-1 reservoir?

2016

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Current antiretroviral therapies have improved the duration and quality of life of people living with HIV-1. However, viral reservoirs impede complete eradication of the virus. Although there are many strategies to eliminate infectious virus, the most actively pursued are latency reversing agents in conjunction with immune modulation. This strategy, known as “shock and kill”, has been tested primarily against the most widely recognized HIV-1 latent reservoir found in resting memory CD4+ T cells. This is in part because of the dearth of conclusive evidence about the existence of non-T cell reservoirs. Studies of non-T cell reservoirs have been difficult to interpret because of technical and biological issues that have hampered a better understanding. This review considers the current knowledge of non-T cell reservoirs, the challenges encountered in a better understanding of these populations, and their implications for HIV-1 cure research.

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Section: Usual and Unusual Suspectsmentioning

confidence: 99%

Are T cells the only HIV-1 reservoir?

2016

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“…Similarly, Iser et al observed increased HIV reverse transcriptase activity following HIV infection of hepatocyte cell lines [26]. Recently, our group demonstrated that both CXCR4- and CCR5-utilizing HIVs can infect hepatocyte cell lines, as well as primary hepatocytes [27]. Moreover, it has been shown that human hepatoma cells can transmit surface bound HIV to CD4+ T cells [28].…”

Section: Introductionsupporting

confidence: 52%

Effects of HCV on Basal and Tat-Induced HIV LTR Activation

et al. 2013

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Hepatitis C virus (HCV) co-infection occurs in ∼30–40% of the HIV-infected population in the US. While a significant body of research suggests an adverse effect of HIV on HCV replication and disease progression, the impact of HCV on HIV infection has not been well studied. Increasing data suggest that hepatocytes and other liver cell populations can serve as reservoirs for HIV replication. Therefore, to gain insight into the impact of HCV on HIV, the effects of the HCV Core protein and infectious hepatitis C virions were evaluated on basal and Tat-induced activation of the HIV long terminal repeat (LTR) in hepatocytes. The HIV LTR was highly induced by the HIV transactivator protein Tat in hepatocytes. Activation varied according to the number of NF-kB binding sites present in the LTRs from different HIV subtypes. Involvement of the NF-kB binding pathway in LTR activation was demonstrated using an NF-kB inhibitor and deletion of the NF-kB binding sites. TNFα, a pro-inflammatory cytokine that plays an important role in HIV pathogenesis, also induced LTR activity in hepatocytes. However, HIV LTR activity was suppressed in hepatocytes in the presence of HCV Core protein, and the suppressive effect persisted in the presence of TNFα. In contrast, infectious hepatitis C virions upregulated HIV LTR activation and gene transcription. Core-mediated suppression remained unaltered in the presence of HCV NS3/4A protein, suggesting the involvement of other viral/cellular factors. These findings have significant clinical implications as they imply that HCV could accelerate HIV disease progression in HIV/HCV co-infected patients. Such analyses are important to elucidate the mechanisms by which these viruses interact and could facilitate the development of more effective therapies to treat HIV/HCV co-infection.

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“…We previously reported that integrated HIV DNA was detected in Huh7.5 and Huh7.5 JFH1 cells, as well as in primary hepatocytes, after in vitro infection [27]. Several antiretroviral agents inhibited HIV infection of hepatocytes, although HIV levels were modest compared to those in a lymphocyte cell line.…”

Section: Resultsmentioning

confidence: 99%

HIV Infection of Hepatocytes Results in a Modest Increase in Hepatitis C Virus Expression In Vitro

et al. 2014

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Previous studies demonstrate that soluble HIV proteins impact both hepatocyte function and HCV replication in vitro. It has also been reported that HIV can productively infect hepatocytes. We therefore investigated the impact of HIV infection of hepatocytes on HCV expression. The Huh7.5JFH1 cell line that constitutively expresses infectious HCV was infected with the lab-adapted strains HIVNL4-3 or HIVYK-JRCSF. HCV expression was quantified via HCV core antigen ELISA, Western blot, and strand-specific real-time PCR for positive-sense and negative-sense HCV RNA. After HIVNL4-3 infection of Huh7.5JFH1 cells, positive-sense and negative-sense HCV RNA levels were elevated compared to HIV uninfected cells. Increased HCV RNA synthesis was also observed after infection of Huh7.5JFH1 cells with HIVYK-JRCSF. HIV-induced HCV core production was decreased in the presence of the anti-HIV drugs AZT, T20, and raltegravir, although these medications had a minimal effect on HCV expression in the absence of HIV. HCV core, NS3, and NS5A protein expression were increased after HIV infection of Huh7.5JFH1 cells. Chemically inactivated HIV had a minimal effect on HCV expression in Huh7.5JFH1 cells suggesting that ongoing viral replication was critical. These data demonstrate that HIV induces HCV RNA synthesis and protein production in vitro and complement previous in vivo reports that HCV RNA levels are elevated in individuals with HIV/HCV co-infection compared to those with HCV mono-infection. These findings suggest that HIV suppression may be a critical factor in controlling liver disease, particularly if the underlying liver disease is not treated.

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Low-level HIV infection of hepatocytes

Cited by 47 publications

References 50 publications

Are T cells the only HIV-1 reservoir?

Are T cells the only HIV-1 reservoir?

Effects of HCV on Basal and Tat-Induced HIV LTR Activation

HIV Infection of Hepatocytes Results in a Modest Increase in Hepatitis C Virus Expression In Vitro

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