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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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Martin-Carbonero, LuzAuthorDe Los Santos, IgnacioAuthor
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Article

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

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

Authors: 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

Affiliations

Hosp Puerta Hierro, Serv Med Interna, Madrid 28222, Spain - Author
Hosp Univ La Princesa, Serv Med Interna Infecciosas, Madrid 28006, Spain - Author
Hosp Univ Ramon y Cajal, Madrid 28034, Spain - Author
Infanta Leonor Hosp, Dept Infect Dis, Madrid 28031, Spain - Author
Inst Hlth Carlos III, Natl Ctr Microbiol, AIDS Immunopathol Unit, Madrid 28220, Spain - Author
Inst Hlth Carlos III, Natl Ctr Microbiol, Lab Reference & Res Viral Hepatitis, Madrid 28220, Spain - Author
Inst Invest Biomed Hosp Doce Octubre imas12, Unidad VIH, Serv Med Interna, Madrid 28041, Spain - Author
Inst Invest Sanitaria Hosp Paz IdiPAZ, Dept Infect Dis, Madrid 28046, Spain - Author
Inst Ramon y Cajal Invest Sanitaria IRYCIS, Serv Enfermedades Infecciosas, Madrid 28034, Spain - Author
Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol, Dept Immunol, Madrid 28220, Spain - Author
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Abstract

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.

Keywords
coinfectionhiv reservoirhiv/hcvqpcrresting cd4+ t lymphocytestatAntiretroviral therapyCoinfectionEradicationHcvHivHiv reservoirHiv/hcvInfectionLatent reservoirMessenger-rnaPeripheral-bloodProvirusesQpcrReplicationResting cd4+ t lymphocytesResting cd4+t lymphocytesTatTranscriptionType-1Viral splicing

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal of Clinical Medicine due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 39/167, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, General & Internal.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-05-18:

  • WoS: 3
  • Scopus: 3
  • Europe PMC: 4
  • OpenCitations: 3
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 12.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 17.35.
  • The number of mentions on the social network X (formerly Twitter): 12 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.