Impact of Hepatitis B Virus Coinfection on Human T-Lymphotropic Virus Type 1 Clonality in an Indigenous Population of Central Australia

Turpin, Jocelyn; Yurick, David; Khoury, Georges; Pham, Hai; Locarnini, Stephen; Melamed, Anat; Witkover, Aviva; Wilson, Kim; Purcell, Damian; Bangham, Charles R. M.; Einsiedel, Lloyd

doi:10.1093/infdis/jiy546

Cited by 16 publications

(12 citation statements)

References 15 publications

(46 reference statements)

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“…For example, in participant P8, sequences from the provirus integrated in the PAFAH1B1 gene represented 87% of all HIV-1 sequences from CMV-responding cells and 22% of those from cells responding to anti-CD3/CD28 ( Figure 2C and S4). To compare the clonality of HIV-1-infected cells across conditions, we used the Gini coefficient, a measure of distribution previously used to estimate oligoclonality in HTLV-1 infection (45). Proviral populations from CMV-responding cells showed significantly higher oligoclonality than those from Gag-or anti-CD3/28-responding cells ( Figure 2E).…”

Section: Identical Proviral Sequences Are Common Among Ag-specific Cementioning

confidence: 99%

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo

Simonetti

Zhang

Soroosh

et al. 2020

Preprint

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Clonal expansion of infected CD4+ T cells is a major mechanism of HIV-1 persistence and a barrier to cure. Potential causes are homeostatic proliferation, effects of HIV-1 integration, and interaction with antigens. Here we show that it is possible to link antigen responsiveness, full proviral sequence, integration site, and T cell receptor β-chain (TCRβ) sequence to examine the role of recurrent antigenic exposure in maintaining the HIV-1 reservoir. We isolated Cytomegalovirus (CMV)- and Gag-responding CD4+ T cells from 10 treated individuals. Proviral populations in CMV-responding cells were dominated by large clones, including clones harboring replication-competent proviruses. TCRβ repertoires showed high clonality driven by converging adaptive responses. Although some proviruses were in genes linked to HIV-1 persistence (BACH2, STAT5B, MKL1), proliferation of infected cells under antigenic stimulation occurred regardless of the site of integration. Paired TCRβ-integration site analysis showed that infection could occur early or late in the course of a clone's response to antigen and could generate infected cell populations too large to be explained solely by homeostatic proliferation. Together these findings implicate antigen-driven clonal selection as a major factor in HIV-1 persistence, a finding that will be a difficult challenge to eradication efforts.

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Section: Identical Proviral Sequences Are Common Among Ag-specific Cementioning

confidence: 99%

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo

Simonetti

Zhang

Soroosh

et al. 2020

Preprint

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“…appear in the list of the top 20 in the 3 cohorts. The prevalence of HTLV-1 and HBV coinfection is high in certain indigenous Australian populations [41]. According to a population-based analysis [42], annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy

et al. 2020

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Background: Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis. Methods: The Gene Expression Omnibus datasets (GSE83148, GSE84044 and GSE66698) were collected and the differentially expressed genes (DEGs), key biological processes and intersecting pathways were analyzed. The expression of the co-expressed DEGs in the clinical samples was verified by quantitative real time polymerase chain reaction (qRT-PCR). Results: Analysis of all the 3 datasets revealed that there were eight up-regulated and one down-regulated coexpressed DEGs following the HBV infection and after IFN-α treatment. In clinical samples, the mRNA level of HKDC1, EPCAM, GSN, ZWINT and PLD3 were significantly increased, while, the mRNA level of PLEKHA2 was significantly decreased in HBV infected liver tissues compared to normal liver tissues. PI3K-Akt signaling pathway, focal adhesion, HTLV-I infection, cytokine-cytokine receptor interaction, metabolic pathways, NF-κB signaling pathway were important pathways associated with the HBV infection and the response of IFN-α treatment. Conclusions: The co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in HBV infection and response of IFN-α treatment. The dysregulated genes may act as novel biomarkers and therapeutic targets for HBV.

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“…Indeed, HBV infection was detected in 19.2% and 15.9% of HTLV-1–seropositive indigenous adults admitted to Alice Springs Hospital (ASH) in Central Australia and patients in Northern Australia, respectively. Coinfection with HTLV-1 and HBV has previously been described in South America and southern Japan 76…”

Section: Coinfection/comorbidity Is More Probable Within Members Of Tmentioning

confidence: 91%

<p>The Binary Classification Of Chronic Diseases</p>

Elkoshi

2019

JIR

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Acute diseases start with an insult and end when insult disappears. If the trauma induces an immune reaction (which happens in most cases), this reaction must be terminated with some type of resolution mechanism, when the cause of the trauma ceases. Chronicity develops if insult is permanent or if the resolution mechanism is defective. Another way to reach disease chronicity is a positive feedback loop, whereby the immune reaction activates an internal, insult-like reaction. A distinction between chronic states characterized by a persistent, low suppressive effect and those characterized by a persistent, high suppressive effect of regulatory T cells (Treg), is proposed. This two-class division represents two ways to reach chronicity: (a) by maintaining inflammatory reaction long after insult disappears (“low Treg”), or (b) by suppressing inflammatory reaction prior to the disappearance of insult (“high Treg”). This two-class division may explain the strong association between certain pathogens and cancer, on one hand, and between several other pathogens and autoimmunity, on the other hand. The weak association between autoimmune diseases and HIV infection and the relatively weak association between autoimmune diseases and cancer may be elucidated as well. In addition, the model rationalizes why immune-modulating drugs, which are effective in cancer, are also effective in “high Treg” viral infections, while corticosteroids, which are generally effective in autoimmune diseases, are also effective in other “low Treg” diseases (such as asthma, atopic dermatitis, and “low Treg” infections) but are not effective in solid malignancies and “high Treg” infections. Moreover, the model expounds why certain bacteria inhibit tumor growth and why these very bacteria induce autoimmune diseases.

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Impact of Hepatitis B Virus Coinfection on Human T-Lymphotropic Virus Type 1 Clonality in an Indigenous Population of Central Australia

Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) and hepatitis B virus coinfection is frequent in certain Indigenous Australian populations, but its outcome remains unknown. We report a higher degree of HTLV-1 clonal expansion than in those with HTLV-1 alone.

Cited by 16 publications

References 15 publications

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo

Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy

<p>The Binary Classification Of Chronic Diseases</p>

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Impact of Hepatitis B Virus Coinfection on Human T-Lymphotropic Virus Type 1 Clonality in an Indigenous Population of Central Australia

Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) and hepatitis B virus coinfection is frequent in certain Indigenous Australian populations, but its outcome remains unknown. We report a higher degree of HTLV-1 clonal expansion than in those with HTLV-1 alone.

Cited by 16 publications

References 15 publications

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4+T cellsin vivo

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4+T cellsin vivo

Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy

<p>The Binary Classification Of Chronic Diseases</p>

Contact Info

Product

Resources

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Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo

Antigen-driven clonal selection shapes the persistence of HIV-1 infected CD4⁺T cellsin vivo