HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy

Zerbato, Jennifer M.; Avihingsanon, Anchalee; Singh, Kasha; Zhao, Wei; Deléage, Claire; Rosen, Elias P.; Cottrell, Mackenzie L.; Rhodes, Ajantha; Dantanarayana, Ashanti; Tumpach, Carolin; Tennakoon, Surekha; Crane, Megan; Price, David; Braat, Sabine; Mason, Hugh S.; Roche, Michael; Kashuba, Angela D. M.; Revill, Peter; Audsley, Jennifer; Lewin, Sharon R

doi:10.1016/j.ebiom.2022.104391

Cited by 14 publications

(8 citation statements)

References 98 publications

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“…For the liver, the susceptibility of its components to HIV-1 has been studied. Both in vivo and in vitro studies have shown the ability of HIV-1 to infect hepatocytes ( Xiao et al., 2008 ; Kong et al., 2012 ; Zerbato et al., 2022 ). An in vitro study verified that HIV-1 can infect hepatic satellite cells ( Tuyama et al., 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans

Zhou

Ren

Yau

2023

Front. Cell. Infect. Microbiol.

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Comprehensive identification of possible target cells for viruses is crucial for understanding the pathological mechanism of virosis. The susceptibility of cells to viruses depends on many factors. Besides the existence of receptors at the cell surface, effective expression of viral genes is also pivotal for viral infection. The regulation of viral gene expression is a multilevel process including transcription, translational initiation and translational elongation. At the translational elongation level, the translational efficiency of viral mRNAs mainly depends on the match between their codon composition and cellular translational machinery (usually referred to as codon adaptation). Thus, codon adaptation for viral ORFs in different cell types may be related to their susceptibility to viruses. In this study, we selected the codon adaptation index (CAI) which is a common codon adaptation-based indicator for assessing the translational efficiency at the translational elongation level to evaluate the susceptibility to two-pandemic viruses (HIV-1 and SARS-CoV-2) of different human cell types. Compared with previous studies that evaluated the infectivity of viruses based on codon adaptation, the main advantage of our study is that our analysis is refined to the cell-type level. At first, we verified the positive correlation between CAI and translational efficiency and strengthened the rationality of our research method. Then we calculated CAI for ORFs of two viruses in various human cell types. We found that compared to high-expression endogenous genes, the CAIs of viral ORFs are relatively low. This phenomenon implied that two kinds of viruses have not been well adapted to translational regulatory machinery in human cells. Also, we indicated that presumptive susceptibility to viruses according to CAI is usually consistent with the results of experimental research. However, there are still some exceptions. Finally, we found that two viruses have different effects on cellular translational mechanisms. HIV-1 decouples CAI and translational efficiency of endogenous genes in host cells and SARS-CoV-2 exhibits increased CAI for its ORFs in infected cells. Our results implied that at least in cases of HIV-1 and SARS-CoV-2, CAI can be regarded as an auxiliary index to assess cells’ susceptibility to viruses but cannot be used as the only evidence to identify viral target cells.

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Section: Resultsmentioning

confidence: 99%

Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans

Zhou

Ren

Yau

2023

Front. Cell. Infect. Microbiol.

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“… 47 , 48 HIV-1 DNA has also been detected in various tissues, including liver and adipose tissue, although it has not yet been shown to be intact/competent for replication. 49 , 50 Concerning the gut, consistently higher levels of total HIV-1 DNA levels were found compared to PBMCs, but intact provirus levels had not been assessed in the gut compartment, 22 , 23 , 24 except in a few people with HIV-1. 26 , 27 We therefore performed a detailed characterization of the HIV-1 reservoir in the intestinal mucosa, sampling different segments of the intestinal tract of people with HIV-1 with sustained undetectable viral load on ART for a mean of 8 years.…”

Section: Discussionmentioning

confidence: 99%

Intact proviruses are enriched in the colon and associated with PD-1+TIGIT− mucosal CD4+ T cells of people with HIV-1 on antiretroviral therapy

Vellas,

Nayrac,

Collercandy

et al. 2024

eBioMedicine

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“…Participants were recruited as part of a larger multi-centre cross sectional and longitudinal cohort which had multiple aims related to liver disease pathogenesis in HIV-HBV co-infection 25 and HIV persistence in the liver. 26 As part of this exploratory analysis, effect sizes and confidence intervals in addition to p-values are reported to support interpretation of the results.…”

Section: Methodsmentioning

confidence: 99%

Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy

Singh,

Avihingsanon,

Zerbato

et al. 2024

eBioMedicine

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HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy

Cited by 14 publications

References 98 publications

Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans

Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans

Intact proviruses are enriched in the colon and associated with PD-1+TIGIT− mucosal CD4+ T cells of people with HIV-1 on antiretroviral therapy

Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy

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