Hepatitis C Virus Influences HIV-1 Viral Splicing in Coinfected Patients



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Martínez-Román, Paula and López-Huertas, María Rosa and Crespo Bermejo, Celia and Arca Lafuente, Sonia and Cortegano, Isabel and Valle-Millares, Daniel and Gaspar, María Luisa and Martín-Carbonero, Luz and Domínguez-Domínguez, Lourdes and Ryan, Pablo and de los Santos, Ignacio and de la Fuente-Moral, Sara and Fernández-Rodríguez, Amanda and Coiras, Mayte and Briz, Verónica (2020) Hepatitis C Virus Influences HIV-1 Viral Splicing in Coinfected Patients. Journal of Clinical Medicine, 9 (7). p. 2091. ISSN 2077-0383

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Official URL: https://doi.org/10.3390/jcm9072091


Coinfection with hepatitis C virus (HCV) influences HIV reservoir size. However, it is unknown whether this coinfection also induces a higher provirus transcription. Viral transcription is promoted by synergy between cellular factors such as NF-κB and the viral regulator Tat. The impact of HCV coinfection on HIV provirus transcription was analyzed in resting (r)CD4 T+ cells (CD3+CD4+CD25-CD69-HLADR-) and rCD4 T cells-depleted PBMCs (rCD4 T- PBMCs) from a multicenter cross-sectional study of 115 cART-treated HIV patients: 42 HIV+/HCV+ coinfected individuals (HIV+/HCV+), 34 HIV+ patients with HCV spontaneous clearance (HIV+/HCV−) and 39 HIV patients (HIV+). Viral transcription was assessed in total RNA through the quantification of unspliced, single spliced, and multiple spliced viral mRNAs by qPCR. Linear correlations between viral reservoir size and viral splicing were determined. A 3-fold increase of multiple spliced transcripts in rCD4 T+ cells of HIV+/HCV+ patients was found compared to HIV+ individuals (p < 0.05). As Tat is synthesized by multiple splicing, the levels of Tat were also quantified in these patients. Significant differences in single and multiple spliced transcripts were also observed in rCD4 T- PBMCs. Levels of multiple spliced mRNAs were increased in rCD4 T+ cells isolated from HIV+/HCV+ subjects, which could indicate a higher Tat activity in these cells despite their resting state.

Item Type:Article
Uncontrolled Keywords:viral splicing; HIV/HCV; coinfection; HIV reservoir; resting CD4+ T lymphocytes; qPCR; Tat
Subjects:Medical sciences > Medicine > Communicable diseases
ID Code:67569
Deposited On:31 Aug 2021 07:55
Last Modified:06 Sep 2021 09:13

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