Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells

Fromentin, Rémi; Tardif, Maurice; Tremblay, Michel J.

doi:10.1099/vir.0.028746-0

Cited by 11 publications

(10 citation statements)

References 63 publications

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“…Our results corroborate the findings of other investigators that human hepatocytes and hepatocytic cell lines can be infected with HIV-1 (3,6,22,70). In contrast, some human hepatoma cell lines lack both CD4 and CXCR4 at the cell surface and are not productively infected with X4-tropic HIV-1 strains (16). This discrepancy could relate to methodological differences used to detect cell surface receptors or the loss of or altered HIV-1 coreceptor expression due to multiple passages of the cell lines.…”

Section: Discussionsupporting

confidence: 90%

HIV-1 Coinfection and Morphine Coexposure Severely Dysregulate Hepatitis C Virus-Induced Hepatic Proinflammatory Cytokine Release and Free Radical Production: Increased Pathogenesis Coincides with Uncoordinated Host Defenses

El‐Hage

Dever

Fitting

et al. 2011

J Virol

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Section: Discussionsupporting

confidence: 90%

HIV-1 Coinfection and Morphine Coexposure Severely Dysregulate Hepatitis C Virus-Induced Hepatic Proinflammatory Cytokine Release and Free Radical Production: Increased Pathogenesis Coincides with Uncoordinated Host Defenses

El‐Hage

Dever

Fitting

et al. 2011

J Virol

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“…The presence of the late HIV protein p24 at day 1-2 post-infection could be due to internalization of the viral particles in hepatocytes and prolonged p24 expression until it is degraded. In fact, lysosome was reported to participate in p24 degradation [43]. Because ethanol metabolism suppresses lysosome function and biogenesis [49], we observed higher p24 levels in hepatocytes treated with AGS.…”

Section: Discussionmentioning

confidence: 62%

“…This rapid clearance of HIV-infected hepatocytes partially explains low reverse transcriptase (RT) activity in cell supernatants. In the literature, there are several very controversial reports on HIV DNA integration even in the absence of AGS: while some authors demonstrated HIV DNA integration and low levels of productive infection in hepatocytes [7,35], others did not support this evidence [43]. In fact, our experimental conditions, which allow the detection of HIV DNA integration in hepatocytes in the presence of AGS, are artificial because this phenomenon can be observed only when apoptosis in infected hepatocytes is prevented by PCI (in vitro conditions).…”

Section: Discussionmentioning

confidence: 99%

Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease

et al. 2019

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In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause of morbidity and mortality, resulting in death in 15–17% of human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated liver damage and promotes the progression to advanced fibrosis and cirrhosis. However, the mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation of HIV in hepatocytes, causing oxidative stress and intensive apoptotic cell death. Engulfment of HIV-containing apoptotic hepatocytes by non-parenchymal cells (NPCs) triggers their activation and liver injury progression. This study was performed on primary human hepatocytes and Huh7.5-CYP cells infected with HIV-1ADA, and major findings were confirmed by pilot data obtained on ethanol-fed HIV-injected chimeric mice with humanized livers. We demonstrated that ethanol exposure potentiates HIV accumulation in hepatocytes by suppressing HIV degradation by lysosomes and proteasomes. This leads to increased oxidative stress and hepatocyte apoptosis. Exposure of HIV-infected apoptotic hepatocytes to NPCs activates the inflammasome in macrophages and pro-fibrotic genes in hepatic stellate cells. We conclude that while HIV and ethanol metabolism-triggered apoptosis clears up HIV-infected hepatocytes, continued generation of HIV-expressing apoptotic bodies may be detrimental for progression of liver inflammation and fibrosis due to constant activation of NPCs.

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“…In fact, several studies confirmed that HIV-1 productive infection in primary hepatocytes and hepatoma cell lines is CD4-independent[ 55 , 57 - 59 ]. Another optional entry for HIV in hepatocytes is through plasma membrane glycosphingolipids, such as Glycolipid galactosyl ceramide[ 60 ]. Usually, the level of HIV-infection in hepatocytes is low, but can be significantly potentiated by second hits like co-infection[ 53 ] or alcohol.…”

Section: Hiv and Liver Cellsmentioning

confidence: 99%

Liver as a target of human immunodeficiency virus infection

Ganesan¹,

Poluektova²,

Kharbanda³

et al. 2018

WJG

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Liver injury is a characteristic feature of human immunodeficiency virus (HIV) infection, which is the second most common cause of mortality in HIV-infected patients. Now it is recognized that liver plays a key role in HIV infection pathogenesis. Antiretroviral therapy (ART), which suppresses HIV infection in permissive immune cells, is less effective in hepatocytes, thereby making these cells a silent reservoir of HIV infection. In addition to direct hepatotoxic effects of HIV, certain ART treatment modalities provide hepatotoxic effects. The exact mechanisms of HIV-triggered chronic hepatitis progression are not elucidated, but the liver is adversely affected by HIV-infection and liver cells are prominently involved in HIV-elicited injury. These effects are potentiated by second hits like alcohol. Here, we will focus on the incidence of HIV, clinical evidence of HIV-related liver damage, interactions between HIV and liver cells and the role of alcohol and co-infection with hepatotropic viruses in liver inflammation and fibrosis progression.

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Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells

Cited by 11 publications

References 63 publications

HIV-1 Coinfection and Morphine Coexposure Severely Dysregulate Hepatitis C Virus-Induced Hepatic Proinflammatory Cytokine Release and Free Radical Production: Increased Pathogenesis Coincides with Uncoordinated Host Defenses

HIV-1 Coinfection and Morphine Coexposure Severely Dysregulate Hepatitis C Virus-Induced Hepatic Proinflammatory Cytokine Release and Free Radical Production: Increased Pathogenesis Coincides with Uncoordinated Host Defenses

Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease

Liver as a target of human immunodeficiency virus infection

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