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Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients

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Abstract

Purpose

To investigate the contribution of SAMHD1 to HIV-1 infection in vivo and its relationship with IFN response, the expression of SAMHD1 and IFN-related pathways was evaluated in HIV-1-infected patients.

Methods

Peripheral blood mononuclear cells (PBMC) from 388 HIV-1-infected patients, both therapy naïve (n = 92) and long-term HAART treated (n = 296), and from 100 gender and age-matched healthy individuals were examined. CD4+ T cells, CD14+ monocytes and gut biopsies were also analyzed in HIV-1-infected subjects on suppressive antiretroviral therapy. Gene expression levels of SAMDH1, ISGs (MxA, MxB, HERC5, IRF7) and IRF3 were evaluated by real-time RT-PCR assays.

Results

SAMHD1 levels in HIV-1-positive patients were significantly increased compared to those in healthy donors. SAMHD1 expression was enhanced in treated patients compared to naïve patients (p < 0.0001) and healthy donors (p = 0.0038). Virologically suppressed treated patients exhibited higher SAMHD1 levels than healthy donors (p = 0.0008), viraemic patients (p = 0.0001) and naïve patients (p < 0.0001). SAMHD1 levels were also increased in CD4+ T cells compared to those in CD14+ monocytes and in PBMC compared to those of GALT. Moreover, SAMHD1 was expressed more strongly than ISGs in HIV-1-infected patients and positive correlations were found between SAMHD1, ISGs and IRF3 levels.

Conclusions

SAMHD1 is more strongly expressed than the classical IFN-related genes, increased during antiretroviral therapy and correlated with ISGs and IRF3 in HIV-1-infected patients.

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Funding

This work was supported by a grant to C.S. (Carolina Scagnolari) from Sapienza University of Rome (Finanziamenti di ateneo per la ricerca scientifica - anno 2017, RM11715C586062AF).

Author information

Authors and Affiliations

  1. Laboratory of Virology, Department of Molecular Medicine, Affiliated to Istituto Pasteur Italia, Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy

    Maura Statzu, Letizia Santinelli, Agnese Viscido, Claudia Rotondo, Ombretta Turriziani, Guido Antonelli & Carolina Scagnolari

  2. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy

    Claudia Pinacchio, Giancarlo Ceccarelli, Giuseppe Corano Scheri & Gabriella d’Ettorre

  3. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Ivano Mezzaroma

Authors
  1. Maura Statzu
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  2. Letizia Santinelli
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  3. Agnese Viscido
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  4. Claudia Pinacchio
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  5. Giancarlo Ceccarelli
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  6. Claudia Rotondo
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  7. Giuseppe Corano Scheri
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  8. Ivano Mezzaroma
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  9. Ombretta Turriziani
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  10. Guido Antonelli
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  11. Gabriella d’Ettorre
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  12. Carolina Scagnolari
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Contributions

MS wrote the paper, carried out the experiment and performed statistical analysis. LS, AV, CP, and CR collected the samples and participated in carrying out the experiments. IM, GC and GD provided patient’s samples and participated in the design and revision of the manuscript. OT and GA participated in the design and revision of the manuscript. CS conceived the study, analyzed the data, wrote the paper and supervised the work. All authors reviewed the work and approved the final manuscript.

Corresponding author

Correspondence to Carolina Scagnolari.

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The authors declare no potential conflict of interest.

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Edited by: O.T. Keppler.

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Statzu, M., Santinelli, L., Viscido, A. et al. Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients. Med Microbiol Immunol 208, 679–691 (2019). https://doi.org/10.1007/s00430-018-0574-x

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  • DOI: https://doi.org/10.1007/s00430-018-0574-x

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