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.

Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients / Statzu, Maura; Santinelli, Letizia; Viscido, Agnese; Pinacchio, Claudia; Ceccarelli, Giancarlo; Rotondo, Claudia; Corano Scheri, Giuseppe; Mezzaroma, Ivano; Turriziani, Ombretta; Antonelli, Guido; D'Ettorre, Gabriella; Scagnolari, Carolina. - In: MEDICAL MICROBIOLOGY AND IMMUNOLOGY. - ISSN 0300-8584. - (2018), pp. 1-14. [10.1007/s00430-018-0574-x]

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

Statzu, Maura
Primo
;
Santinelli, Letizia;Viscido, Agnese;Pinacchio, Claudia;Ceccarelli, Giancarlo;Rotondo, Claudia;Corano Scheri, Giuseppe;Mezzaroma, Ivano;Turriziani, Ombretta;Antonelli, Guido;d'Ettorre, Gabriella
Penultimo
;
Scagnolari, Carolina
Ultimo
2018

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.
2018
HIV-1; IFN; IRF3; ISG; SAMHD1
01 Pubblicazione su rivista::01a Articolo in rivista
Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients / Statzu, Maura; Santinelli, Letizia; Viscido, Agnese; Pinacchio, Claudia; Ceccarelli, Giancarlo; Rotondo, Claudia; Corano Scheri, Giuseppe; Mezzaroma, Ivano; Turriziani, Ombretta; Antonelli, Guido; D'Ettorre, Gabriella; Scagnolari, Carolina. - In: MEDICAL MICROBIOLOGY AND IMMUNOLOGY. - ISSN 0300-8584. - (2018), pp. 1-14. [10.1007/s00430-018-0574-x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1243762
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