title: SAMHD1 specifically restricts retroviruses through its RNase activity.
abstract: BACKGROUND
  Human SAMHD1 possesses dual enzymatic functions. It acts as both a dGTP-dependent triphosphohydrolase and as an exoribonuclease. The dNTPase function depletes the cellular dNTP pool, which is required for retroviral reverse transcription in differentiated myeloid cells and resting CD4(+) T cells; thus this activity mainly plays a role in SAMHD1-mediated retroviral restriction. However, a recent study demonstrated that SAMHD1 directly targets HIV-1 genomic RNA via its RNase activity, and that this function (rather than dNTPase activity) is sufficient for HIV-1 restriction. While HIV-1 genomic RNA is a potent target for SAMHD1 during viral infection, the specificity of SAMHD1-mediated RNase activity during infection by other viruses is unclear.
  
  
  RESULTS
  The results of the present study showed that SAMHD1 specifically degrades retroviral genomic RNA in monocyte-derived macrophage-like cells and in primary monocyte-derived macrophages. Consistent with this, SAMHD1 selectively restricted retroviral replication, but did not affect the replication of other common non-retro RNA genome viruses, suggesting that the RNase-mediated antiviral function of SAMHD1 is limited to retroviruses. In addition, neither inhibiting reverse transcription by treatment with several reverse transcriptase inhibitors nor infection with reverse transcriptase-defective HIV-1 altered RNA levels after viral challenge, indicating that the retrovirus-specific RNase function is not dependent on processes associated with retroviral reverse transcription.
  
  
  CONCLUSIONS
  The results presented herein suggest that the RNase activity of SAMHD1 is sufficient to control the replication of retroviruses, but not that of non-retro RNA viruses.
authors.affiliation: Creative Research Initiative Center for Antigen Presentation, Seoul National University, Seoul, Republic of Korea. jschoi1980@snu.ac.kr.|Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea. jschoi1980@snu.ac.kr.
authors.forename: Jongsu
authors.initials: J
authors.lastname: Choi
authors.affiliation: Creative Research Initiative Center for Antigen Presentation, Seoul National University, Seoul, Republic of Korea. ryu0219@snu.ac.kr.|Department of the Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea. ryu0219@snu.ac.kr.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Ryoo
authors.affiliation: Creative Research Initiative Center for Antigen Presentation, Seoul National University, Seoul, Republic of Korea. soojunggoo@gmail.com.|Department of the Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea. soojunggoo@gmail.com.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Oh
authors.affiliation: Creative Research Initiative Center for Antigen Presentation, Seoul National University, Seoul, Republic of Korea. overhsy@snu.ac.kr.|Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea. overhsy@snu.ac.kr.
authors.forename: Sungyeon
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Creative Research Initiative Center for Antigen Presentation, Seoul National University, Seoul, Republic of Korea. ksahn@snu.ac.kr.|Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea. ksahn@snu.ac.kr.
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
mesh_terms: D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000821:virology; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012190:Retroviridae / Q000276:immunology* / Q000502:physiology; D012260:Ribonucleases / Q000378:metabolism*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D012260:Ribonucleases; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins