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

Autor: María Rosa López-Huertas, Mayte Coiras, Daniel Valle-Millares, Lourdes Domínguez-Domínguez, Celia Crespo-Bermejo, Sara de la Fuente-Moral, Ignacio Santos, Pablo Ryan, Paula Martínez-Román, María Luisa Gaspar, Luz Martín-Carbonero, Sonia Arca-Lafuente, Verónica Briz, Isabel Cortegano, Amanda Fernández-Rodríguez
Přispěvatelé: Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III - ISCIII, Fondo de Investigaciones Sanitarias, European Regional Development Fund (ERDF/FEDER), Red Española de Investigación en SIDA, Instituto de Salud Carlos III, European Regional Development Fund
Rok vydání: 2020
Předmět:
Zdroj: Repisalud
Instituto de Salud Carlos III (ISCIII)
E-Prints Complutense. Archivo Institucional de la UCM
instname
Journal of Clinical Medicine
Journal of Clinical Medicine, Vol 9, Iss 2091, p 2091 (2020)
Volume 9
Issue 7
Popis: 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&minus
) 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.
Databáze: OpenAIRE