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Financial support was provided by the Instituto de Salud Carlos III to VB and AFR (PI15CIII/00031 and PI18CIII/00020), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016-78480-R), and the SPANISH AIDS Research Network RD16CIII/0002/0001 and RD16CIII/0002/0002-ISCIII-FEDER. A.F.R. is supported by the Miguel Servet programme from Fondo de Investigacion Sanitaria (ISCIII) (CP14/CIII/00010).

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

Publicado en:Journal of Clinical Medicine. 9 (7): 2091-18 - 2020-07-01 9(7), DOI: 10.3390/jcm9072091

Autores: Martinez-Roman, Paula; Rosa Lopez-Huertas, Maria; Crespo-Bermejo, Celia; Arca-Lafuente, Sonia; Cortegano, Isabel; Valle-Millares, Daniel; Luisa Gaspar, Maria; Martin-Carbonero, Luz; Dominguez-Dominguez, Lourdes; Ryan, Pablo; de los Santos, Ignacio; de la Fuente-Moral, Sara; Fernandez-Rodriguez, Amanda; Coiras, Mayte; Briz, Veronica

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Resumen

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-kappa B 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.

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