A central role for PI3K-AKT signaling pathway in linking SAMHD1-deficiency to the type I interferon signature DOI Creative Commons
Changhoon Oh, Jeongmin Ryoo, Kiwon Park

et al.

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Jan. 2, 2018

The autoimmune disorder Aicardi-Goutières syndrome (AGS) is characterized by a constitutive type I interferon response. SAMHD1 possesses both dNTPase and RNase activities mutations in cause AGS; however, how SAMHD1-deficiency causes the response patients with AGS remains unknown. Here, we show that endogenous RNA substrates accumulated absence of act as major immunogenic source for Reconstitution SAMHD1-negative human cells wild-type but not RNase-defective abolishes spontaneous induction. We further identify PI3K/AKT/IRF3 signaling pathway essential SAMHD1-deficient monocytic cells. Treatment PI3K or AKT inhibitors dramatically reduces signatures Moreover, SAMHD1/AKT1 double knockout relieves to levels observed Identification AGS-related sensing provides critical insights into molecular pathogenesis interferonopathies such overlapping disorders.

Language: Английский

Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1 DOI Creative Commons
Gi Uk Jeong,

Il-Hyun Park,

Kwangseog Ahn

et al.

Virology, Journal Year: 2016, Volume and Issue: 495, P. 71 - 78

Published: May 11, 2016

Language: Английский

Citations

40
Impaired influenza A virus replication by the host restriction factor SAMHD1 which inhibited by PA-mediated dephosphorylation of the host transcription factor IRF3 DOI Creative Commons
Zhilei Zhao, Shuyi Han, Qingxun Zhang

et al.

Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 29, 2024

Abstract Background Influenza A virus (IAV) can cause severe and life-threatening illness in humans animals. Therefore, it is important to search for host antiviral proteins elucidate their mechanisms the development of potential treatments. As a part human innate immunity, restriction factors inhibit replication viruses, among which SAM HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) restrict such as HIV enterovirus EV71. Viruses also developed countermeasures arms race with hosts. There are few reports about whether SAMHD1 has effect on IAV. Methods To investigate impact IAV infection expression A549 cells, we infected cells varying multiplicity (MOI) collected cell samples at different time points WB RT-qPCR analysis detect viral protein levels. The level culture supernatant was determined using TCID50 assay. Luciferase assay used reveal that H5N1 polymerase acidic (PA) affected activity promoter. assess capacity SAMHD1, generated knockdown overexpressed line detecting replication. Results In this study, observed intracellular PA downregulate by affecting transcriptional promoter activity. We found SAMHD1's ability related phosphorylation 592-tyrosine. Conclusions conclusion, may affect IAVs factor be countered PA. Furthermore, target developing drugs.

Language: Английский

Citations

4
Roles of SAMHD1 in antiviral defense, autoimmunity and cancer DOI
Miaomiao Li, Dong Zhang, Mengying Zhu

et al.

Reviews in Medical Virology, Journal Year: 2017, Volume and Issue: 27(4)

Published: April 25, 2017

The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells resting CD4+ T cells. This dNTP degradation reduces the concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. antiviral enzymatic activity can be inhibited X (Vpx). HIV-2/SIV Vpx causes SAMHD1, thus interfering with SAMHD1-mediated restriction Recently, SAMHD1 has been suggested restrict HIV-1 directly digesting genomic RNA through still controversial RNase activity. Here, we summarize current knowledge about structure, mechanisms, localization, interferon-regulated expression SAMHD1. We also describe SAMHD1-deficient animal models an drug on basis disrupting proteasomal In addition, possible roles regulating innate immune sensing, Aicardi-Goutières syndrome cancer are discussed this review.

Language: Английский

Citations

37
CD81 association with SAMHD1 enhances HIV-1 reverse transcription by increasing dNTP levels DOI
Vera Rocha‐Perugini,

Henar Suárez,

Susana Álvarez

et al.

Nature Microbiology, Journal Year: 2017, Volume and Issue: 2(11), P. 1513 - 1522

Published: Sept. 1, 2017

Language: Английский

Citations

37
A central role for PI3K-AKT signaling pathway in linking SAMHD1-deficiency to the type I interferon signature DOI Creative Commons
Changhoon Oh, Jeongmin Ryoo, Kiwon Park

et al.

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Jan. 2, 2018

The autoimmune disorder Aicardi-Goutières syndrome (AGS) is characterized by a constitutive type I interferon response. SAMHD1 possesses both dNTPase and RNase activities mutations in cause AGS; however, how SAMHD1-deficiency causes the response patients with AGS remains unknown. Here, we show that endogenous RNA substrates accumulated absence of act as major immunogenic source for Reconstitution SAMHD1-negative human cells wild-type but not RNase-defective abolishes spontaneous induction. We further identify PI3K/AKT/IRF3 signaling pathway essential SAMHD1-deficient monocytic cells. Treatment PI3K or AKT inhibitors dramatically reduces signatures Moreover, SAMHD1/AKT1 double knockout relieves to levels observed Identification AGS-related sensing provides critical insights into molecular pathogenesis interferonopathies such overlapping disorders.

Language: Английский

Citations

35