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Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein
Open accessAbstract
Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
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In the citing paper
“This approach was necessary because PU.1 is the master transcriptional regulator necessary for macrophage differentiation and silencing PU.1 prior to infection results in a change in the cellular phenotype that causes resistance to HIV infection72,73.”
From HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages (2024) · cites this paper as [73]
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“It was then determined that Vpx may facilitate the association of SAMHD1 with this complex to promote its proteasome-dependent degradation.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [81]
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“Upon MS analysis, the cellular innate immune protein SAMHD1 was the most spectrally abundant association with the Vpx-E3 ubiquitin ligase complex.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [81]
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In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Trex1 prevents cell-intrinsic initiation of autoimmunity
Stetson, D. B., Ko, J. S., Heidmann, T., & Medzhitov, R. (2008) · Cell · doi:10.1016/j.cell.2008.06.032 · Cited by 1,280
Dendritic Cells: Translating Innate to Adaptive Immunity
Steinman, R. M., & Hemmi, H. (2006) · Springer eBooks · doi:10.1007/3-540-32636-7_2 · Cited by 855
A quantitative assay for HIV DNA integration in vivo
Butler, S. L., Hansen, M. S., & Bushman, F. D. (2001) · Nature Medicine · doi:10.1038/87979 · Cited by 695
Rice, G., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.373 · Cited by 686
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674
The Challenge of Viral Reservoirs in HIV-1 Infection
Blankson, J. N., Persaud, D., & Siliciano, R. F. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104024 · Cited by 649 · cited 1×
“MDM were subjected to RNAi targeting DCAF1, SAMHD1 or non-targeting RNAi (NT1, NT2), and infected (1) or not (2) with SIV VLP loaded with SIVmac Vpx, 2 days later.”
MethodTrex1 Exonuclease Degrades ssDNA to Prevent Chronic Checkpoint Activation and Autoimmune Disease
Yang, Y., Lindahl, T. L., & Barnes, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.10.017 · Cited by 574
Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells
Manel, N., Hogstad, B., Wang, Y., Levy, D. E., Unutmaz, D., & Littman, D. R. (2010) · Nature · doi:10.1038/nature09337 · Cited by 427
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Cellular metabolism in the defense against microbes
Pernas, L. F. (2021) · Journal of Cell Science · doi:10.1242/jcs.252023 · Cited by 19
“For example, although lentiviral reverse transcriptases can function in relatively low dNTPs environments, host factors like SAMHD1 further deplete dNTPs to inhibit viral replication (Baldauf et al., 2012; Diamond et al., 2004; Lahouassa et al., 2012).”
BackgroundInfluentialSingle-cell analysis reveals divergent responses of human dendritic cells to the MVA vaccine
Döring, M., de Azevedo, K., Blanco-Rodriguez, G., Nadalin, F., Satoh, T., Gentili, M., Lahaye, X., Silva, N. S. D., Conrad, C., Jouve, M. J., et al. (2021) · Science Signaling · doi:10.1126/scisignal.abd9720 · Cited by 24
Evidence for Vpr-dependent HIV-1 Replication in Human CD4+CEM.NKR T-Cells
Zhou, T., Dang, Y., Baker, J. J., Zhou, J., & Zheng, Y. (2012) · Retrovirology · doi:10.1186/1742-4690-9-93 · Cited by 20
“As introduced earlier, Vpx neutralizes the restriction factor SAMHD1, and this activity is DCAF1-dependent [32].”
Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice
Schmitt, K. P., Kumar, D. M., Curlin, J., Remling‐Mulder, L., Stenglein, M. D., O’Connor, S. L., Marx, P. A., & Akkina, R. (2017) · Virology · doi:10.1016/j.virol.2017.07.005 · Cited by 21
“, 2004); (3) SAMHD1, which acts by depleting the cellular dNTP pool available for reverse transcription (Berger et al., 2011; Goldstone et al., 2011; Hrecka et al., 2011); (4) SERINC3/5 (serine incorporator 3 and 5), acts by inhibiting the early stages of viral infection by impairing the penetration of the viral parti…”
BackgroundTrinité, B., Chan, C. N., Lee, C. S., & Levy, D. N. (2016) · Journal of Virology · doi:10.1128/jvi.01770-15 · Cited by 19
“It has been recently demonstrated that the cellular protein SAMHD1, which is constitutively expressed in several nondividing cell types such as monocytes/macrophages (47), dendritic cells (48, 49), and resting CD4 T cells (50), functions as a FIG 6 Early HIV-1-induced death of resting peripheral blood T cells results…”
BackgroundCoon, S., Wang, D., & Wu, L. J. (2012) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2012.0039 · Cited by 20
“In contrast, Vpx of less pathogenic HIV type 2 (HIV-2) and certain simian immunodeficiency viruses (such as SIVsm lineage) can induce proteolytic degradation of SAMHD1 and relieve SAMHD1mediated viral restriction in human myeloid cells.(15,16) The lack of Vpx in HIV-1 may benefit HIV-1 as an immune evasion strategy fo…”
Wei, W., Guo, H., Gao, Q., Markham, R. B., & Yu, X. (2013) · Journal of Virology · doi:10.1128/jvi.02866-13 · Cited by 19
“Vpx binds DCAF1 by using conserved motifs in helix 1 and helix 3, which in turn recruit other components of the CRL4(DCAF1) E3 ubiquitin ligase (35– 41) to facilitate SAMHD1 ubiquitination and subsequent degradation (18, 20, 22, 35, 36, 38, 39, 41).”
BackgroundMereby, S. A., Maehigashi, T., Holler, J. M., Kim, D., Schinazi, R. F., & Kim, B. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004567 · Cited by 19
“A series of recent studies revealed that host SAM domain– and HD domain–containing protein 1 (SAMHD1) restrictsHIV-1 inmyeloid cells (12, 13) by using its dNTP triphosphohydrolase (dNTPase) activity (14) and is also responsible for the lowdNTPconcentration found in macrophages (15, 16).”
BackgroundMethodInfluentialLandsberg, C. D., Megger, D. A., Hotter, D., Rückborn, M. U., Eilbrecht, M., Rashidi‐Alavijeh, J., Howe, S., Heinrichs, S., Sauter, D., Sitek, B., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02978 · Cited by 20
Ubiquitination and SUMOylation in HIV Infection: Friends and Foes
Colomer-Lluch, M., Castro‐Gonzalez, S., & Serra-Moreno, R. (2019) · Current Issues in Molecular Biology · doi:10.21775/cimb.035.159 · Cited by 21
“…E3 ubiquitin ligase complex, inducing SAMHD1 poly-ubiquitination and proteasomal degradation, thereby favouring HIV reverse transcription in both resting CD4+ T cells and myeloid cells (Bergamaschi et al., 2009; Hrecka et al., 2011; Laguette et al., 2011; Ahn et al., 2012) (Table 24.1).”
BackgroundInfluentialCCCH-type zinc finger antiviral protein mediates antiviral immune response by activating T cells
Zhu, M., Zhou, J., Liang, Y., Nair, V., Yao, Y., & Cheng, Z. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ab1119-314rrr · Cited by 19
Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration
Kishimoto, N., Yamamoto, K., Iga, N., Kirihara, C., Abe, T., Takamune, N., & Misumi, S. (2020) · Retrovirology · doi:10.1186/s12977-020-00539-9 · Cited by 19
HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7
Zhou, X., Monnie, C. M., DeLucia, M., & Ahn, J. (2021) · Virology Journal · doi:10.1186/s12985-021-01514-2 · Cited by 20
Zaongo, S. D., Ouyang, J., Chen, Y., Jiao, Y., Wu, H., & Chen, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.853346 · Cited by 20
Degradation of SAMHD1 by Vpx Is Independent of Uncoating
Jáuregui, P., Logue, E. C., Schultz, M. L., Fung, S., & Landau, N. R. (2015) · Journal of Virology · doi:10.1128/jvi.03575-14 · Cited by 22
“Knockdown of DCAF1 prior to infection prevented the Vpxinduced degradation of SAMHD1, consistent with previous findings (1, 2, 37, 55), but knockdown of DDB1 had no effect.”
MethodResultHIV-2 Vpx Protein Interacts with Interferon Regulatory Factor 5 (IRF5) and Inhibits Its Function
Cheng, X., & Ratner, L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.534321 · Cited by 20
“Vpx binds SAMHD1 and recruits it to the CRL4 E3 ubiquitin ligase via its interaction with DCAF1 to facilitate SAMHD1 ubiquitination and subsequent degradation (27, 28, 33, 34).”
BackgroundWalker-Sperling, V. E. K., Buckheit, R. W., & Blankson, J. N. (2014) · Journal of Virology · doi:10.1128/jvi.00860-14 · Cited by 19
Tsunetsugu‐Yokota, Y., & Muhsen, M. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00178 · Cited by 23
“…a study on Vpx. SIV virus like particles (VLPs) containing Vpx are known to enhance the expression of VSV-G-pseudotyped lentivirus in DC (Santini et al., 2000), and this finding lead to the identification of SAMHD1, a myeloid cell restriction factor (Caminschi et al., 2008; Hrecka et al., 2011).”
BackgroundHuman Immunodeficiency Virus Infection and Host Defense in the Lungs
Charles, T. P., & Shellito, J. E. (2016) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0036-1572553 · Cited by 19
Schejtman, A., Aragão-Filho, W. C., Clare, S., Zinicola, M., Weisser, M., Burns, S. O., Booth, C., Gaspar, H. B., Thomas, D., Condino‐Neto, A., et al. (2020) · Gene Therapy · doi:10.1038/s41434-020-0164-6 · Cited by 19
Meo, S. D., Dell’Oste, V., Molfetta, R., Tassinari, V., Lotti, L. V., Vespa, S., Pignoloni, B., Covino, D. A., Fantuzzi, L., Bona, R., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008855 · Cited by 19
Maarifi, G., Lagisquet, J., Hertel, Q., Bonaventure, B., Chamontin, C., Fuchs, K. J., Moncorgé, O., Tauziet, M., Mombled, M., Papin, L., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106540 · Cited by 16
“More precisely, this anti-HIV activity was shown to act at the reverse transcription (RT) step and SAMHD1, a previously reported HIV restriction factor (Hrecka et al , 2011; Laguette et al , 2011), was seemingly not required.”
Banchenko, S., Krupp, F., Gotthold, C., Bürger, J., Graziadei, A., O’Reilly, F. J., Sinn, L. R., Ruda, O., Rappsilber, J., Spahn, C. M. T., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009775 · Cited by 17
“Importantly, Vpx also recruits the SAMHD1 restriction factor to DCAF1, in order to mark it for proteasomal destruction [37,38].”
BackgroundQin, Y., Li, Y., Liu, W., Tian, R., Guo, Q., Li, S., Li, H., Zhang, D., Zheng, Y., Wu, L. J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027609 · Cited by 19
“The antiretroviral protein, namely SAMHD1 (SAM domain HD domain-containing protein 1), has been recently identified to inhibit the early step of HIV-1 replication in dendritic- and myeloid cells [47,48].”
BackgroundDual anti-HIV mechanism of clofarabine
Daly, M. B., Roth, M. E., Bonnac, L. F., Maldonado, J. O., Xie, J., Clouser, C. L., Patterson, S. E., Kim, B., & Mansky, L. M. (2016) · Retrovirology · doi:10.1186/s12977-016-0254-0 · Cited by 18
“Interestingly, unlike HIV-1, HIV-2 and many SIVs encode a viral accessory protein, viral protein X (Vpx), that counteracts SAMHD1 and promotes retroviral replication in macrophages by elevating cellular dNTPs [13, 15, 16].”
BackgroundHIV Fusion in Dendritic Cells Occurs Mainly at the Surface and Is Limited by Low CD4 Levels
Chauveau, L., Donahue, D. A., Monel, B., Porrot, F., Bruel, T., Richard, L., Casartelli, N., & Schwartz, O. (2017) · Journal of Virology · doi:10.1128/jvi.01248-17 · Cited by 23
Forlani, G., Shallak, M., Ramia, E., Tedeschi, A., & Accolla, R. S. (2019) · Retrovirology · doi:10.1186/s12977-019-0498-6 · Cited by 20
Nucleotide embargo by SAMHD1: A strategy to block retroviral infection
Pauls, E., Ballana, E., & Esté, J. A. (2012) · Antiviral Research · doi:10.1016/j.antiviral.2012.12.009 · Cited by 19
Schaller, T., Goujon, C., & Malim, M. H. (2012) · Science · doi:10.1126/science.1221057 · Cited by 22
Anti-HIV Factors: Targeting Each Step of HIV's Replication Cycle
Colomer-Lluch, M., Gollahon, L., & Serra-Moreno, R. (2016) · Current HIV Research · doi:10.2174/1570162x14999160224094621 · Cited by 17
Morris, E. R., Kunzelmann, S., Caswell, S. J., Purkiss, A. G., Kelly, G. P., & Taylor, I. A. (2021) · Biochemistry · doi:10.1021/acs.biochem.0c00944 · Cited by 17
SARS‐CoV‐2, HIV, and HPV: Convergent evolution of selective regulation of cGAS–STING signaling
Shen, S., Rui, Y., Wang, Y., Su, J., & Yu, X. (2022) · Journal of Medical Virology · doi:10.1002/jmv.28220 · Cited by 17
Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion
Mohanty, S., & Harhaj, E. W. (2023) · Pathogens · doi:10.3390/pathogens12050735 · Cited by 18
“HIV-1 Vpx to prevent antiviral immune responses [80].”
RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR
Yang, W., Wang, H., Li, Z., Zhang, L., Liu, J., Kirchhoff, F., Huan, C., & Zhang, W. (2024) · Nature Communications · doi:10.1038/s41467-024-49622-1 · Cited by 18
The role of tripartite motif family members in mediating susceptibility to HIV-1 infection
Rahm, N., & Telenti, A. (2012) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32835048e1 · Cited by 20
Cellular and Biochemical Mechanisms of the Retroviral Restriction Factor SAMHD1
Wu, L. J. (2013) · ISRN Biochemistry · doi:10.1155/2013/728392 · Cited by 19
“The authors further demonstrated that the inhibition of HIV-1 infection in monocyte-derived macrophages by Vpxmediated proteasome degradation of SAMHD1 through the cellular E3 ubiquitin ligase complex [22].”
BackgroundThe role of HIV-1 Vpr in promoting the infection of nondividing cells and in cell cycle arrest
Sharifi, H. J., Furuya, A. K. M., & de Noronha, C. M. C. (2012) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32835049e0 · Cited by 19
Czubala, M. A., Finsterbusch, K., Ivory, M. O., Mitchell, J. P., Ahmed, Z., Shimauchi, T., Karoo, R. O. S., Coulman, S. A., Gateley, C., Birchall, J. C., et al. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.123 · Cited by 20
“…Interferon alpha (IFN α ) is a potent antiviral cytokine which increases expression of several HIV-1 cellular restriction factors and interferon stimulated genes (ISG) (Blanchet et al, 2013, Goujon et al, 2013, Kane et al, 2013, Van Damme et al, 2008) and restricts HIV-1 infection in myeloid cells.”
BackgroundInlora, J., Chukkapalli, V., Bedi, S., & Ono, A. (2016) · Journal of Virology · doi:10.1128/jvi.01004-16 · Cited by 19
“Myeloid cells, including macrophages, express high levels of a restriction factor known as SAM domain- and HD domain-containing protein 1 (SAMHD1), which suppresses HIV-1 replication (90, 91).”
BackgroundNucleocytoplasmic shuttling of SAMHD1 is important for LINE-1 suppression
Du, J., Peng, Y., Wang, S., Hou, J., Wang, Y., Sun, T., & Zhao, K. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.009 · Cited by 22
Dai, L., Lidie, K. B., Chen, Q., Adelsberger, J. W., Zheng, X. M., Huang, D.-W., Yang, J., Lempicki, R. A., Rehman, T. U., Dewar, R. L., et al. (2013) · Cytokine · doi:10.1016/j.cyto.2013.06.061 · Cited by 18
HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription
Ivanov, A. I., Lin, X., Ammosova, T., Ilatovskiy, A. V., Kumari, N., Lassiter, H., Afangbedji, N. K. A., Niu, X., Petukhov, M., & Nekhai, S. A. (2018) · Retrovirology · doi:10.1186/s12977-018-0422-5 · Cited by 17
Positive selection in dNTPase SAMHD1 throughout mammalian evolution
Monit, C., Morris, E. R., Ruis, C., Szafran, B., Thiltgen, G., Tsai, M.-H., Mitchison, N. A., Bishop, K. N., Stoye, J. P., Taylor, I. A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908755116 · Cited by 16
A Potent Postentry Restriction to Primate Lentiviruses in a Yinpterochiropteran Bat
Morrison, J. H., Miller, C. M., Bankers, L., Crameri, G. S., Wang, L., & Poeschla, E. M. (2020) · mBio · doi:10.1128/mbio.01854-20 · Cited by 20
“Equine infectious anemia virus (EIAV) packaging and eGFP transfer plasmids (74), SIVmac251 vector plasmids (SIV3 ) (38), and human-pathogenic foamy virus vector plasmids (75) were used as indicated.”
BackgroundMethodDeubiquitinating Enzyme USP21 Inhibits HIV-1 Replication by Downregulating Tat Expression
Gao, W., Li, G., Zhao, S., Wang, H., Huan, C., Zheng, B., Jiang, C., & Zhang, W. (2021) · Journal of Virology · doi:10.1128/jvi.00460-21 · Cited by 17
“HIV accessory proteins Vif, Vpx, and Vpr recruit host E3 ubiquitin ligase complexes to induce polyubiquitination of the host restriction factors A3G, SAMHD1, and HLTF (1, 2, 4, 5, 29), whereas Vpu is involved in BST-2 degradation through the proteasomal or lysosomal pathways (30).”
BackgroundInfluentialZhao, Z., Li, Z., Huan, C., Liu, X., & Zhang, W. (2021) · Journal of Virology · doi:10.1128/jvi.00620-21 · Cited by 16
Orris, B., Huynh, K. W., Ammirati, M. J., Han, S., Bolaños, B., Carmody, J., Petroski, M. D., Bosbach, B., Shields, D. J., & Stivers, J. T. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac573 · Cited by 17
Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction
Ahn, J. (2016) · Biological Chemistry · doi:10.1515/hsz-2015-0260 · Cited by 20
“With a similar methodology, Hrecka et al., identified SAMHD1-Vpx complexes in HEK293T cells and found that Vpx mediates proteasome-dependent down-regulation of SAMHD1, by loading it onto an E3 ubiquitin ligase, cullin ring- finger ligase 4 (CRL4)-DDB1- and cullin-associated factor 1 (DCAF1) (Hrecka et al., 2011).”
BackgroundInfluentialLong-term HIV-1 infection induces an antiviral state in primary macrophages
Pujantell, M., Badía, R., Ramirez, C., Puig, T., Clotet, B., Ballana, E., Esté, J. A., & Riveira‐Muñoz, E. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2016.08.004 · Cited by 18
Lodge, R., Gilmore, J. C., Barbosa, J. F., Lombard‐Vadnais, F., & Cohen, É. A. (2017) · Viruses · doi:10.3390/v10010013 · Cited by 20
“Similarly, expression of antiviral host factors such as sterile alpha-motif, histidine-aspartic domain-containing protein 1 (SAMHD1) that reduces the pool of cellular deoxyribonucleotides available for reverse transcription influence the levels of productive HIV-1 replication in macrophages [19,20].”
BackgroundHuman interleukin-34-derived macrophages have increased resistance to HIV-1 infection
Paquin‐Proulx, D., Greenspun, B. C., Kitchen, S. M., Raposo, R. A. S., Nixon, D. F., & Grayfer, L. (2018) · Cytokine · doi:10.1016/j.cyto.2018.09.006 · Cited by 18
Izumida, M., Suga, K., Ishibashi, F., & Kubo, Y. (2019) · Marine Drugs · doi:10.3390/md17090495 · Cited by 17
“For examples, SAM domain- and HD domain-containing protein 1 (SAMHD1) inhibits HIV-1 infection of dendritic cells [2,3] and T cells [4,5] by reducing the cellular deoxynucleoside triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function [2,6].”
BackgroundZhang, Z., Zheng, L., Yu, Y., Wu, J., Yang, F., Xu, Y., Guo, Q., Wu, X., Cao, S., Cao, L., et al. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.4988 · Cited by 15
“More specifically, studies on the underlying mechanisms of antiviral agents to fight infection have revealed that SAMHD1 inhibits HIV-1 infection in non-dividing cells by restricting viral reverse transcription, resulting in decreased virus activity and storage (14,15,113,114).”
BackgroundMultiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo
Aso, H., Nagaoka, S., Kawakami, E., Ito, J., Islam, S., Tan, B. J. Y., Nakaoka, S., Ashizaki, K., Shiroguchi, K., Suzuki, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107887 · Cited by 17
P-Selectin Glycoprotein Ligand 1: A Potential HIV-1 Therapeutic Target
Zaongo, S. D., Liu, Y., Harypursat, V., Song, F., Xia, H., Ma, P., & Chen, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.710121 · Cited by 17
“Tripartite motif-containing protein 5-a (TRIM5-a) (18), APOBEC3 (19), tetherin (20), SAM domain and HD domaincontaining protein 1 (SAMHD1) (21, 22), and serine incorporator 3 (SERINC3)/SERINC5 (23, 24) are examples of a few restriction factors identified thus far.”
BackgroundThippeshappa, R., Ruan, H., Wang, W., Zhou, P., & Kimata, J. T. (2013) · Journal of Virology · doi:10.1128/jvi.00338-13 · Cited by 17
Ju, S. M., Goh, A. R., Kwon, D.-J., Youn, G. S., Kwon, H., Bae, Y. S., Choi, S. Y., & Park, J. (2012) · Molecules and Cells · doi:10.1007/s10059-012-2287-0 · Cited by 19
“(4) Finally, SAMHD1 was recently identified to inhibit HIV-1 infection in human dendritic cells and myeloid cells (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundVorontsov, I. I., Wu, Y., DeLucia, M., Minasov, G., Mehrens, J., Shuvalova, L., Anderson, W. F., & Ahn, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.524207 · Cited by 17
“The virulence factor Vpx in HIV-2 and simian immunodeficiency virus antagonizes SAMHD1 by directing it for proteasome-dependent degradation (9, 10, 14).”
BackgroundPoly-proline motif in HIV-2 Vpx is critical for its efficient translation
Miyake, A., Fujita, M., Fujino, H., Koga, R., Kawamura, S., Otsuka, M., Ode, H., Iwatani, Y., Sakai, Y., Doi, N., et al. (2013) · Journal of General Virology · doi:10.1099/vir.0.057364-0 · Cited by 18
“Recently, it has been demonstrated that Vpx induces proteasomal degradation of host factors SAMHD1 (Hrecka et al., 2011; Laguette et al., 2011) and APOBEC3A (Berger et al., 2011), relieving the restriction of virus infection.3These authors contributed equally to this work.”
BackgroundLatent human cytomegalovirus enhances HIV-1 infection in CD34+ progenitor cells
Cheung, A. K. L., Huang, Y., Kwok, H., Chen, M., & Chen, Z. (2017) · Blood Advances · doi:10.1182/bloodadvances.2016000638 · Cited by 18
Viral Manipulations of the Cullin-RING Ubiquitin Ligases
Liu, Y., & Tan, X. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1025-0_7 · Cited by 17
SAMHD1: A Novel Antiviral Factor in Intrinsic Immunity
Chen, Z., Zhang, L., & Ying, S. (2012) · Future Microbiology · doi:10.2217/fmb.12.81 · Cited by 17
Gene Transduction in Human Monocyte-Derived Dendritic Cells Using Lentiviral Vectors
Satoh, T., & Manel, N. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-218-6_30 · Cited by 20
Bayliss, R., Wheeldon, J., Caucheteux, S. M., Niessen, C. M., & Piguet, V. (2020) · Journal of Virology · doi:10.1128/jvi.01597-19 · Cited by 17
Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing
Scott, T. M., Arnold, L. M., Powers, J. A., McCann, D., Rowe, A. B., Christensen, D. E., Pereira, M. J. B., Zhou, W., Torrez, R. M., Iwasa, J., et al. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1012206 · Cited by 16
“Human monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs) can be infected by HIV-1, particularly when the lentiviral accessory protein Vpx is provided in trans to overcome SAMHD1-mediated restriction in MDDCs [59,60].”
A Highly Active Isoform of Lentivirus Restriction Factor SAMHD1 in Mouse
Bloch, N., Gläsker, S., Sitaram, P., Hofmann, H., Shepard, C., Schultz, M. L., Kim, B., & Landau, N. R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.743740 · Cited by 17
“The lentiviral restriction factor SAMHD1(2) is a dNTP triphosphohydrolase (1, 2) that inhibits the replication of HIV-1 in myeloid cells (3, 4).”
BackgroundHIV-1 trans-Infection Mediated by DCs: The Tip of the Iceberg of Cell-to-Cell Viral Transmission
Perez‐Zsolt, D., Regué, D. R., Muñoz‐Basagoiti, J., Aguilar‐Gurrieri, C., Clotet, B., Blanco, J., & Izquierdo‐Useros, N. (2021) · Pathogens · doi:10.3390/pathogens11010039 · Cited by 18
“Noteworthy, DCs are non-permissive to HIV-1 infection, as they express low levels of viral receptor and co-receptors [69], efficiently degrade incoming viruses [70,71] and express several restriction factors such as SAMHD1 that interfere with viral replication [72–77].”
BackgroundValeri, E., Unali, G., Piras, F., Alezz, M. A., Pais, G., Benedicenti, F., Lidonnici, M. R., Cuccovillo, I., Castiglioni, I., Arévalo, S., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.11.020 · Cited by 17
“10,11 However, counter-acting SAMHD1 through the accessory viral protein Vpx or the addition of exogenous dNs did not signi fi cantly improve transduction of stimulated HSPC. 12 As the antiviral activity of SAMHD1 is limited to non-cycling cells where dNTP availability is already restricted, we…”
The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes
Roubille, S., Escure, T., Juillard, F., Corpet, A., Néplaz, R., Binda, O., Seurre, C., Gonin, M., Bloor, S., Cohen, C., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2412258121 · Cited by 19
Cellular Restriction Factors of Feline Immunodeficiency Virus
Zielonka, J., & Münk, C. (2011) · Viruses · doi:10.3390/v3101986 · Cited by 16
“Recently, the human protein SAMHD1 was identified to be causative for the post-entry restriction of HIV-1 in myeloid cells [126,127].”
Mouse knockout models for HIV-1 restriction factors
Rehwinkel, J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1646-8 · Cited by 18
“Two proteomic studies identified SAMHD1 as a host protein co-purifying with vpx [67, 68].”
BackgroundResultInfluentialRevising the Role of Myeloid cells in HIV Pathogenesis
Aggarwal, A., McAllery, S., & Turville, S. G. (2012) · Current HIV/AIDS Reports · doi:10.1007/s11904-012-0149-1 · Cited by 16
Sang, M., Liu, J.-B., Dai, M., Wu, J., & Ho, W. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.10.008 · Cited by 17
“SAMHD1 has the ability to block the infection of HIV before their reverse transcription in resting CD4+ T cells (Baldauf et al., 2012), dendritic cells and macrophages (Hrecka et al., 2011; Laguette et al., 2011).”
Mass Spectrometry-Based Proteomic Approaches for Discovery of HIV–Host Interactions
Luo, Y., & Muesing, M. A. (2014) · Future Virology · doi:10.2217/fvl.14.86 · Cited by 16
Du, C., Liu, H., Lin, Y., Wang, X., Ma, J., Li, Y., Wang, X., & Zhou, J. (2015) · PROTEOMICS · doi:10.1002/pmic.201400279 · Cited by 16
Sadewasser, A., Paki, K., Eichelbaum, K., Bogdanow, B., Saenger, S., Budt, M., Lesch, M., Hinz, K. ‐., Herrmann, A., Meyer, T. F., et al. (2017) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m116.065904 · Cited by 16
Mauney, C. H., Perrino, F. W., & Hollis, T. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b01038 · Cited by 16
Ren, H., Yin, X., Su, C., Guo, M., Wang, X., Lei, N., Lin, Y., & Wang, X. (2020) · Autophagy · doi:10.1080/15548627.2020.1846301 · Cited by 16
How SLX4 cuts through the mystery of HIV-1 Vpr-mediated cell cycle arrest
Blondot, M.-L., Dragin, L., Lahouassa, H., & Margottin-Goguet, F. (2014) · Retrovirology · doi:10.1186/preaccept-2057766064124418 · Cited by 18
Versatility of ARD1/NAA10-mediated protein lysine acetylation
Vo, T. T. L., Jeong, C., Lee, S., Kim, K., Ha, E., & Seo, J. H. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0100-7 · Cited by 18
de Sousa-Pereira, P., Abrantes, J., Bauernfried, S., Pierini, V., Esteves, P. J., Keppler, O. T., Pizzato, M., Hornung, V., Fackler, O., & Baldauf, H. (2018) · Journal of General Virology · doi:10.1099/jgv.0.001201 · Cited by 18
Wu, Y., Koharudin, L. M. I., Mehrens, J., DeLucia, M., Byeon, C., Byeon, I. L., Calero, G. A., Ahn, J., & Gronenborn, A. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665513 · Cited by 17
“For example, Vpx binds DDB1- and Cullin4-associated factor 1 (DCAF1), a substrate receptor of Cullin4 RING E3 ubiquitin ligase (CRL4) and loads SAMHD1 for polyubiquitination, the first step toward degradation (10, 11, 20).”
BackgroundSu, B., Lederle, A., Laumond, G., Ducloy, C., Schmidt, S., Decoville, T., & Moog, C. (2014) · Journal of Virology · doi:10.1128/jvi.01748-14 · Cited by 19
“macaques (SIVmac) (23, 24) but absent in HIV-1 (25, 26).”
BackgroundGuatelli, J., Siliciano, R. F., Kuritzkes, D. R., & Richman, D. D. (2016) · ASM Press eBooks · doi:10.1128/9781555819439.ch34 · Cited by 16
The SAM domain of mouse SAMHD1 is critical for its activation and regulation
Buzovetsky, O., Tang, C., Knecht, K. M., Antonucci, J. M., Wu, L. J., Ji, X., & Xiong, Y. (2017) · Worldwide Protein Data Bank · doi:10.2210/pdb6brg/pdb · Cited by 16
Manipulation of the nucleotide pool in human, bacterial and plant immunity
Hochhauser, D., & Sorek, R. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01206-w · Cited by 17
Coevolutionary dynamics between tribe Cercopithecini tetherins and their lentiviruses
Takeuchi, J. S., Ren, F., Yoshikawa, R., Yamada, E., Nakano, Y., Kobayashi, T., Matsuda, K., Izumi, T., Misawa, N., Shintaku, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep16021 · Cited by 18
Staphylococcus aureus Multiplexes Death-Effector Deoxyribonucleosides to Neutralize Phagocytes
Tantawy, E., Schwermann, N., Ostermeier, T., Garbe, A. I., Bähre, H., Vital, M., & Winstel, V. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.847171 · Cited by 15
“For example, SAMHD1, a dNTPdegrading phosphohydrolase and intracellular enzyme that restricts HIV-1 infection of myeloid cells (60), along with the purine nucleoside phosphorylase PNP affect survival rates of dGuo-exposed cells (58, 59, 61, 62).”
BackgroundInterferon-inducible SAMHD1 restricts viral replication through downregulation of lipid synthesis
An, N. A., Ge, Q., Shao, H., Li, Q., Guo, F., Liang, C., Li, X., Yi, D., Yang, L., & Cen, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1007718 · Cited by 16
“Moreover, HIV Vpx also accelerates ubiquitination of SAMHD1 and is marked for proteasomal degradation (6, 32).”
BackgroundRole of Type I Interferons during Mycobacterium tuberculosis and HIV Infections
Anes, E., Azevedo‐Pereira, J. M., & Pires, D. (2024) · Biomolecules · doi:10.3390/biom14070848 · Cited by 15
“The identification of mutations in the CA protein that allow the virus to evade the action of Mx2 [96–98, SAMHD1 was identified as an HIV-1 restriction factor that blocks early-stage virus replication in dendritic cells (DCs) [110,111].”
BackgroundDeterminants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr
DePaula-Silva, A. B., Cassiday, P. A., Chumley, J., Bosque, A., Monteiro-Filho, C. M., Mahon, C. S., Cone, K. R., Krogan, N. J., Elde, N. C., & Planelles, V. (2015) · Virology · doi:10.1016/j.virol.2014.12.040 · Cited by 15
“Consequently, SAMHD1 diminishes the capacity of the virus to infect macrophages, dendritic cells and quiescent T-cells wherein dNTP levels are normally very low (Hrecka et al., 2011; Laguette et al., 2011b).”
BackgroundMethodResultInfluentialThe eukaryotic elongation factor eEF1A1 interacts with SAMHD1
Morrissey, C., Schwefel, D., Ennis-Adeniran, V., Taylor, I. A., Crow, Y. J., & Webb, M. (2014) · Biochemical Journal · doi:10.1042/bj20140203 · Cited by 17
Wang, T., Xu, Y., Zhu, H., Andrus, T., Ivanov, S. B., Pan, C., Dolores, J. S., Dann, G. C., Zhou, M., Forte, D. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065071 · Cited by 14
“(SAMHD1) [84,85].”
Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
Kermi, C., Lau, L., Shahmirzadi, A. A., & Classon, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.826461 · Cited by 16
“SAMHD1 was initially identified as a cellular restriction factor for Human Immuno-Deficiency Virus-1 (HIV-1) in nondividing myeloid cells (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundSaito, A., Nomaguchi, M., Kono, K., Iwatani, Y., Yokoyama, M., Yasutomi, Y., Sato, H., Shioda, T., Sugiura, W., Matano, T., et al. (2013) · Journal of General Virology · doi:10.1099/vir.0.050252-0 · Cited by 15
Sharifi, H. J., Furuya, A. K. M., Jellinger, R. M., Nekorchuk, M. D., & de Noronha, C. M. C. (2014) · Journal of Virology · doi:10.1128/jvi.00241-14 · Cited by 16
Ménager, M. M. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160439 · Cited by 16
Hakata, Y., Miyazawa, M., & Landau, N. R. (2014) · Virology Journal · doi:10.1186/1743-422x-11-108 · Cited by 13
“By interacting with the CRL4DCAF1 E3 ligase complex, Vpx targets sterile alpha motif domain- and HD domain-containing protein 1 (SAMHD1) for proteasomal degradation to counteract the SAMHD1mediated lentivirus restriction [36,37].”
BackgroundViral evasion of cGAS-STING pathway: opportunities for intervention
Yu, X., Wang, S., Ye, R., & Wei, W. (2025) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2025.08.009 · Cited by 16
Bryostatin-1 Decreases HIV-1 Infection and Viral Production in Human Primary Macrophages
Hany, L., Turmel, M., Barat, C., Ouellet, M., & Tremblay, M. J. (2021) · Journal of Virology · doi:10.1128/jvi.01953-21 · Cited by 14
“SAMHD1 is a highly potent restriction factor in macrophages, preventing viral DNA synthesis and more profoundly affecting completed versus early transcripts (45, 46), reminiscent of the romidepsin-induced pattern.”
Background
Metadata
- Authors
- Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., & Skowronski, J.
- Affiliations
- Case Western Reserve University (US)
- Cold Spring Harbor Laboratory (US)
- Stowers Institute for Medical Research (US)
- Venue
- Nature
- Published
- 2011-06
- Volume
- 474
- Issue
- 7353
- Pages
- 658-661
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3179858
- OpenAlex
- W1964567249
- Cited by
- 1,200
- References
- 30
- Citations by year
- 2026: 30 · 2025: 51 · 2024: 54 · 2023: 47 · 2022: 62 · 2021: 58 · 2020: 66 · 2019: 82 · 2018: 88 · 2017: 87 · 2016: 91 · 2015: 101 · 2014: 125 · 2013: 125 · 2012: 109
- FWCI
- 48.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R21AI084694, R01AI077459)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- HIV-1, Vpx, SAMHD1, macrophages, dendritic cells, host restriction factors, proteasomal degradation, Aicardi-Goutières syndrome, innate immunity, interferon response, retroviral infection, HIV-2, simian immunodeficiency virus
- MeSH terms
- SAM Domain and HD Domain-Containing Protein 1, Carrier Proteins, Cells, Cultured, Humans, Macrophages, Nuclear Proteins, HIV-1, HIV Infections, Protein Serine-Threonine Kinases, Monomeric GTP-Binding Proteins, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Viral Regulatory and Accessory Proteins, HEK293 Cells
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