Cellular and Biochemical Mechanisms of the Retroviral Restriction Factor SAMHD1

Overview

Journal ISRN Biochem

Specialty Biochemistry

Date 2014 Feb 14

PMID 24523981

Citations 16

Authors

Li Wu

Affiliations

Soon will be listed here.

Abstract

Replication of HIV-1 and other retroviruses is dependent on numerous host proteins in the cells. Some of the host proteins, however, function as restriction factors to block retroviral infection of target cells. The host protein SAMHD1 has been identified as the first mammalian deoxynucleoside triphosphate triphosphohydrolase (dNTPase), which blocks the infection of HIV-1 and other retroviruses in non-cycling immune cells. SAMHD1 protein is highly expressed in human myeloid-lineage cells and CD4 T-lymphocytes, but its retroviral restriction function is only observed in non-cycling cells. Recent studies have revealed biochemical mechanisms of SAMHD1-mediated retroviral restriction. In this review, the latest progress on SAMHD1 research is summarized and the mechanisms by which SAMHD1 mediates retroviral restriction are analyzed. Although the physiological function of SAMHD1 is largely unknown, this review provides perspectives about the role of endogenous SAMHD1 protein in maintaining normal cellular function, such as nucleic acid metabolism and the proliferation of cells.

Citing Articles

Aggravating mechanisms from COVID-19.

Lee J, Sergi C, Kast R, Kanwar B, Bourbeau J, Oh S Virol J. 2024; 21(1):228.

PMID: 39334442 PMC: 11430051. DOI: 10.1186/s12985-024-02506-8.

HIV-1 restriction by SERINC5.

Cano-Ortiz L, Luedde T, Munk C Med Microbiol Immunol. 2022; 212(2):133-140.

PMID: 35333966 PMC: 10085909. DOI: 10.1007/s00430-022-00732-x.

SAMHD1 Impairs HIV-1 Gene Expression and Negatively Modulates Reactivation of Viral Latency in CD4 T Cells.

Antonucci J, Kim S, St Gelais C, Bonifati S, Li T, Buzovetsky O J Virol. 2018; 92(15).

PMID: 29793958 PMC: 6052313. DOI: 10.1128/JVI.00292-18.

SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways.

Chen S, Bonifati S, Qin Z, St Gelais C, Kodigepalli K, Barrett B Proc Natl Acad Sci U S A. 2018; 115(16):E3798-E3807.

PMID: 29610295 PMC: 5910870. DOI: 10.1073/pnas.1801213115.

A Cyclin-Binding Motif in Human SAMHD1 Is Required for Its HIV-1 Restriction, dNTPase Activity, Tetramer Formation, and Efficient Phosphorylation.

St Gelais C, Kim S, Maksimova V, Buzovetsky O, Knecht K, Shepard C J Virol. 2018; 92(6).

PMID: 29321329 PMC: 5827405. DOI: 10.1128/JVI.01787-17.

References

Zhou H, Xu M, Huang Q, Gates A, Zhang X, Castle J . Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe. 2008; 4(5):495-504. DOI: 10.1016/j.chom.2008.10.004. View

Schaller T, Goujon C, Malim M . AIDS/HIV. HIV interplay with SAMHD1. Science. 2012; 335(6074):1313-4. DOI: 10.1126/science.1221057. View

Goujon C, Schaller T, Galao R, Amie S, Kim B, Olivieri K . Evidence for IFNα-induced, SAMHD1-independent inhibitors of early HIV-1 infection. Retrovirology. 2013; 10:23. PMC: 3598776. DOI: 10.1186/1742-4690-10-23. View

Fujita M, Otsuka M, Miyoshi M, Khamsri B, Nomaguchi M, Adachi A . Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages. J Virol. 2008; 82(15):7752-6. PMC: 2493314. DOI: 10.1128/JVI.01003-07. View

Ahn J, Hao C, Yan J, DeLucia M, Mehrens J, Wang C . HIV/simian immunodeficiency virus (SIV) accessory virulence factor Vpx loads the host cell restriction factor SAMHD1 onto the E3 ubiquitin ligase complex CRL4DCAF1. J Biol Chem. 2012; 287(15):12550-8. PMC: 3321004. DOI: 10.1074/jbc.M112.340711. View

Jones K, Petrow-Sadowski C, Huang Y, Bertolette D, Ruscetti F . Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells. Nat Med. 2008; 14(4):429-36. DOI: 10.1038/nm1745. View

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Yu H, Usmani S, Borch A, Kramer J, Sturzel C, Khalid M . The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals. Retrovirology. 2013; 10:27. PMC: 3599662. DOI: 10.1186/1742-4690-10-27. View

REICHARD P . Interactions between deoxyribonucleotide and DNA synthesis. Annu Rev Biochem. 1988; 57:349-74. DOI: 10.1146/annurev.bi.57.070188.002025. View

10.

Engelman A, Cherepanov P . The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol. 2012; 10(4):279-90. PMC: 3588166. DOI: 10.1038/nrmicro2747. View

11.

Berger G, Durand S, Fargier G, Nguyen X, Cordeil S, Bouaziz S . APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells. PLoS Pathog. 2011; 7(9):e1002221. PMC: 3178557. DOI: 10.1371/journal.ppat.1002221. View

12.

Schoggins J, Wilson S, Panis M, Murphy M, Jones C, Bieniasz P . A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011; 472(7344):481-5. PMC: 3409588. DOI: 10.1038/nature09907. View

13.

Van Damme N, Goff D, Katsura C, Jorgenson R, Mitchell R, Johnson M . The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008; 3(4):245-52. PMC: 2474773. DOI: 10.1016/j.chom.2008.03.001. View

14.

Welbourn S, Miyagi E, White T, Diaz-Griffero F, Strebel K . Identification and characterization of naturally occurring splice variants of SAMHD1. Retrovirology. 2012; 9:86. PMC: 3503569. DOI: 10.1186/1742-4690-9-86. View

15.

Bieniasz P . Intrinsic immunity: a front-line defense against viral attack. Nat Immunol. 2004; 5(11):1109-15. DOI: 10.1038/ni1125. View

16.

White T, Brandariz-Nunez A, Valle-Casuso J, Amie S, Nguyen L, Kim B . The retroviral restriction ability of SAMHD1, but not its deoxynucleotide triphosphohydrolase activity, is regulated by phosphorylation. Cell Host Microbe. 2013; 13(4):441-51. PMC: 3864637. DOI: 10.1016/j.chom.2013.03.005. View

17.

Sheehy A, Gaddis N, Choi J, Malim M . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002; 418(6898):646-50. DOI: 10.1038/nature00939. View

18.

Goncalves A, Karayel E, Rice G, Bennett K, Crow Y, Superti-Furga G . SAMHD1 is a nucleic-acid binding protein that is mislocalized due to aicardi-goutières syndrome-associated mutations. Hum Mutat. 2012; 33(7):1116-22. DOI: 10.1002/humu.22087. View

19.

Goujon C, Riviere L, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix J . SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells. Retrovirology. 2007; 4:2. PMC: 1779362. DOI: 10.1186/1742-4690-4-2. View

20.

Wu L . Biology of HIV mucosal transmission. Curr Opin HIV AIDS. 2008; 3(5):534-40. PMC: 2542876. DOI: 10.1097/COH.0b013e32830634c6. View