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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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“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]
In the citing paper
“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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“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.”
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Cited by
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Items 401–500 of 1,000
Yu, C. H., Bhattacharya, A., Persaud, M., Taylor, A. B., Wang, Z., Bulnes‐Ramos, Á., Xu, J., Selyutina, A., Martínez‐López, A., Cano, K. E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21023-8 · Cited by 35
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Masters of manipulation: Viral modulation of the immunological synapse
Bayliss, R. J., & Piguet, V. (2018) · Cellular Microbiology · doi:10.1111/cmi.12944 · Cited by 36
Soll, S. J., Wilson, S. J., Kutluay, S. B., Hatziioannou, T., & Bieniasz, P. D. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003667 · Cited by 35
Type I Interferons as Ambiguous Modulators of Chronic Inflammation in the Central Nervous System
Prinz, M., & Knobeloch, K. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00067 · Cited by 36
“Two recent publications identified SAMHD1 as the factor restricting HIV infection in myeloid and dendritic cells and showed that Vpx proteins counteract this restriction by mediating proteasomal degradation of SAMHD1 (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundBallana, E., Badía, R., Terradas, G., Torres‐Torronteras, J., Ruiz, A., Pauls, E., Riveira‐Muñoz, E., Clotet, B., Martí, R., & Esté, J. A. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03145-14 · Cited by 37
“SAMHD1 is counteracted by the retroviral Vpx protein that is encoded by simian immunodeficiency virus (SIV) and HIV-2, but this gene is lacking from the HIV-1 and feline immunodeficiency virus (FIV) genomes (7).”
BackgroundYang, S., Zhan, Y., Zhou, Y., Jiang, Y., Zheng, X., Yu, L., Tong, W., Gao, F., Li, L., Huang, Q., et al. (2016) · Scientific Reports · doi:10.1038/srep29665 · Cited by 38
“HIV-2 and certain strains of SIVsm that encode the Vpx protein utilized the CRL4 DCAF1 and E3 ubiquitin ligase complex to recruit SAMHD1 for proteasome-dependent degradation 10–12 .”
White, T. E., Brandariz-Núñez, A., Martínez‐López, A., Knowlton, C., Lenzi, G. M., Kim, B., Ivanov, D. N., & Diaz‐Griffero, F. (2017) · Human Mutation · doi:10.1002/humu.23201 · Cited by 35
“Because Vpx triggers the degradation of SAMHD1 (Hrecka et al., 2011; Laguette et al., 2011), we tested the ability of Vpx to induce the degradation of the different human SAMHD1 proteins.”
BackgroundMethodValle‐Casuso, J. C., Allouch, A., David, A., Lenzi, G. M., Studdard, L. R., Barré‐Sinoussi, F., Müller-Trutwin, M. C., Kim, B., Pancino, G., & Sáez‐Cirión, A. (2017) · Journal of Virology · doi:10.1128/jvi.01324-17 · Cited by 41
“Although SAMHD1 is expressed in both cycling and noncycling cells, its antiviral activity only occurs in the latter (10, 12, 14, 16, 23, 56).”
Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection
Shtanko, O., Sakurai, Y., Reyes, A. N., Noël, R., Cintrat, J., Gillet, D., Barbier, J., & Davey, R. A. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.11.016 · Cited by 35
Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice
Norton, T. D., Zhen, A., Tada, T., Kim, J. S., Kitchen, S. G., & Landau, N. R. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.008 · Cited by 35
Boso, G., & Kozak, C. A. (2020) · Microorganisms · doi:10.3390/microorganisms8121965 · Cited by 37
Boasso, A. (2013) · Scientifica · doi:10.1155/2013/580968 · Cited by 37
Levesque, S., Cosentino, A., Verma, A., Genovese, P., & Bauer, D. E. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02266-4 · Cited by 39
“The accessory lentiviral protein Vpx, encoded by HIV-2 and simian immunodeficiency viruses (SIVs), associates with the CRL4-DCAF1 E3 ubiquitin ligase to target SAMHD1 for proteasomal degradation 8 .”
Wei, W., Guo, H., Liu, X., Zhang, H., Qian, L., Luo, K., Markham, R. B., & Yu, X. (2013) · Journal of Virology · doi:10.1128/jvi.02568-13 · Cited by 35
Myeloid Cells in Intact Human Cervical Explants Capture HIV and Can Transmit It to CD4 T Cells
Trifonova, R. T., Bollman, B., Barteneva, N. S., & Lieberman, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02719 · Cited by 34
“separated into CD4+ (5) and CD8+ (6) T cells.”
BackgroundMethodDetailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages
Bejarano, D. A., Puertas, M. C., Börner, K., Martínez‐Picado, J., Müller, B., & Kräusslich, H. (2018) · Viruses · doi:10.3390/v10110620 · Cited by 35
“Accordingly, HIV-2 and SIV replicate more efficiently in primary human macrophages than HIV-1 [28], and HIV-1 replication can be experimentally enhanced by SAMHD1 depletion through knock-down or Vpx expression [25,29,30].”
BackgroundCRISPR-Cas based targeting of host and viral genes as an antiviral strategy
Koujah, L., Shukla, D., & Naqvi, A. R. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.04.004 · Cited by 34
“However, transducing the activity of SAMHD1 is counteracted by Viral Protein X (VpX) which targets and degrades the protein, leading to the restoration of dNTP levels and allowing for HIV-1 replication [98,99].”
BackgroundSAMHD1 … and Viral Ways around It
Deutschmann, J., & Gramberg, T. (2021) · Viruses · doi:10.3390/v13030395 · Cited by 33
“In target cells, Vpx induces the proteasomal degradation of SAMHD1 by tying it to the ubiquitin–proteasome system [54,55].”
BackgroundInnate Sensing of Foamy Viruses by Human Hematopoietic Cells
Rua, R., Lepelley, A., Gessain, A., & Schwartz, O. (2011) · Journal of Virology · doi:10.1128/jvi.06235-11 · Cited by 37
“Monocyte-derived DCs are poorly sensitive to HIV-1 infection due to the presence of the SAMHD1 restriction factor (31, 37).”
BackgroundSAMHD1-Dependent and -Independent Functions of HIV-2/SIV Vpx Protein
Fujita, M., Nomaguchi, M., Adachi, A., & Otsuka, M. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00297 · Cited by 37
“…297 | 3 Following the identification of SAMHD1, several investigators showed that although some cells such as undifferentiated THP-1 cells express SAMHD1, both the wild-type HIV-2-type virus and its Vpx mutant infect these cells to an equivalent degree (Hrecka et al., 2011; Planelles, 2011).”
BackgroundInfluentialHUSH, a Link Between Intrinsic Immunity and HIV Latency
Chougui, G., & Margottin-Goguet, F. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00224 · Cited by 35
Gao, Y., Ju, Y., Ren, X., Zhang, L., & Yin, X. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e21886 · Cited by 34
Innate immune interferon responses to Human immunodeficiency virus‐1 infection
Hughes, R. W., Towers, G. J., & Noursadeghi, M. (2012) · Reviews in Medical Virology · doi:10.1002/rmv.1708 · Cited by 36
“Another gene defect associated with AGS is that of SAMHD1, that is also expressed in myeloid cells and recently been shown to mediate post-entry restriction of HIV-1 by targeting viral reverse transcription products [80,81].”
BackgroundGene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1
Chan, E., Towers, G. J., & Qasim, W. (2014) · Viruses · doi:10.3390/v6010243 · Cited by 36
“Subsequently, SAMHD1 was found to be an HIV-1 restriction factor and in dendritic cells, macrophages and quiescent CD4 T cells [45–48].”
BackgroundStructural Basis for the Antiviral Activity of BST-2/Tetherin and Its Viral Antagonism
Arias, J. F., Iwabu, Y., & Tokunaga, K. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00250 · Cited by 39
“…Stremlau et al., 2004); the bone marrow stromal antigen 2 (Neil et al., 2008; Van Damme et al., 2008; BST-2, also known as tetherin or CD317, referred to hereafter as BST-2), which is the subject of this review article; and, more recently, SAMHD1 (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundInfluentialMaudet, C., Sourisce, A., Dragin, L., Lahouassa, H., Rain, J., Bouaziz, S., Ramírez, B. C., & Margottin-Goguet, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077320 · Cited by 37
“For example, the antiviral activity of the SAMHD1 restriction factor can only be unravelled in quiescent cells, where its viral counterpart, Vpx, enhances HIV-1 transduction [2,7,8].”
BackgroundMiazzi, C., Ferraro, P., Pontarin, G., Rampazzo, C., Reichard, P. A., & Bianchi, V. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.571091 · Cited by 36
“Interest in the protein exploded in recent years, when it was discovered that the enzyme via its phosphohydrolase activity (1, 2) serves as a restriction factor during HIV-1 infection (3, 4).”
BackgroundDragin, L., Nguyen, L. A., Lahouassa, H., Sourisce, A., Kim, B., Ramírez, B. C., & Margottin-Goguet, F. (2013) · Retrovirology · doi:10.1186/1742-4690-10-30 · Cited by 38
“As for other viral auxiliary proteins, Vpx usurps the activity of the Cul4A-based ubiquitin ligase through the DCAF1 adaptor, to induce the degradation of SAMHD1 [26,28,49].”
BackgroundInfluentialDCAF1 controls T-cell function via p53-dependent and -independent mechanisms
Guo, Z., Kong, Q., Liu, C., Zhang, S., Zou, L., Yan, F., Whitmire, J. K., Xiong, Y., Chen, X., & Wan, Y. Y. (2016) · Nature Communications · doi:10.1038/ncomms10307 · Cited by 32
Sauter, D., & Kirchhoff, F. (2015) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000233 · Cited by 35
“The accessory protein Vpr and its paralog Vpx of HIV-2 and many SIVs degrade the restriction factor SAMHD1 [45,46,90].”
BackgroundAso, H., Ito, J., Koyanagi, Y., & Sato, K. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00429 · Cited by 32
“This HIV-1 induced IFN-I production triggers ISG expression, and certain ISGs have been thoroughly investigated as ‘restriction factors (RFs)’ or intrinsic immunity that inhibits HIV-1 replication: the apolipoprotein B mRNA editing enzyme catalytic-like 3 (APOBEC3) family [e.g., APOBEC3G (Sheehy et al., 2002)] (review…”
BackgroundVpx-containing dendritic cell vaccine induces CTLs and reactivates latent HIV-1 in vitro
Norton, T. D., Miller, E. A., Bhardwaj, N., & Landau, N. R. (2015) · Gene Therapy · doi:10.1038/gt.2014.117 · Cited by 33
Role of myeloid cells in HIV-1-host interplay
Stevenson, M. (2014) · Journal of NeuroVirology · doi:10.1007/s13365-014-0281-3 · Cited by 36
“The cellular restriction that is targeted by vpx was recently identified as SAMHD1 (Laguette et al. 2011; Hrecka et al. 2011).”
BackgroundTareen, S. U., Kelley-Clarke, B., Nicolai, C. J., Cassiano, L., Nelson, L. T., Slough, M. M., Vin, C. D., Odegard, J., Sloan, D. D., Hoeven, N. V., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.278 · Cited by 32
HIV-derived vectors for therapy and vaccination against HIV
Nunzio, F. D., Félix, T., Arhel, N. J., Nisole, S., Charneau, P., & Beignon, A. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.01.089 · Cited by 34
Functional Analysis of the Relationship between Vpx and the Restriction Factor SAMHD1
Berger, G., Turpin, J., Cordeil, S., Tartour, K., Nguyen, X.-N., Mahieux, R., & Cimarelli, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.403816 · Cited by 35
SAMHD1 Has Differential Impact on the Efficacies of HIV Nucleoside Reverse Transcriptase Inhibitors
Huber, A. D., Michailidis, E., Schultz, M. L., Ong, Y. T., Bloch, N., Puray‐Chavez, M., Leslie, M. D., Ji, J., Lucas, A. D., Kirby, K. A., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02745-14 · Cited by 33
SAMHD1: a new contributor to HIV-1 restriction in resting CD4+T-cells
Wu, L. J. (2012) · Retrovirology · doi:10.1186/1742-4690-9-88 · Cited by 36
“It has been shown that the lentiviral protein Vpx from HIV-2 and sooty mangabey-lineage SIV (SIVsm) counteracts SAMHD1-mediated HIV-1 restriction in myeloid cells through proteasomal degradation of SAMHD1 [5-7].”
The Dynamic Interplay between HIV-1, SAMHD1, and the Innate Antiviral Response
Antonucci, J. M., Gelais, C. S., & Wu, L. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01541 · Cited by 33
“SAMHD1 is constitutively expressed at various levels in all cell types and highly expressed in myeloid lineage and resting CD4+ T-cells (14, 15, 19).”
BackgroundAntonucci, J. M., Kim, S., Gelais, C. S., Bonifati, S., Li, T.-W., Buzovetsky, O., Knecht, K. M., Duchon, A. A., Xiong, Y., Musier‐Forsyth, K., et al. (2018) · Journal of Virology · doi:10.1128/jvi.00292-18 · Cited by 31
“Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is the only identified mammalian deoxynucleoside triphosphate triphosphohydrolase (dNTPase) (1, 2) with a well-characterized role in the downregulation of intracellular deoxynucleoside triphosphate (dNTP) levels (3), a mechanism by which SAMHD1 acts as a…”
BackgroundIlluminating the Role of Vpr in HIV Infection of Myeloid Cells
Nodder, S. B., & Gummuluru, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01606 · Cited by 35
Han, M., Cantaloube-Ferrieu, V., Xie, M., Armani-Tourret, M., Woottum, M., Pagès, J., Colin, P., Lagane, B., & Bénichou, S. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010335 · Cited by 35
“Interestingly, it was also found that in vivo 582 infection of myeloid cells in infected animals occurred irrespective of expression of the SIV 583 Vpx auxiliary protein known to counteract the antiviral host cell restriction factor SAMHD1 584 highly expressed in myeloid cells [85-88].”
BackgroundAntiretroviral restriction factors
Hatziioannou, T., & Bieniasz, P. D. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.10.007 · Cited by 33
“References [75] and [80] report the identification of SAMHD1 as an antiviral protein that is removed by the action of Vpx.”
Wang, B., Kang, W., Zuo, J., 康文臻, & Sun, Y. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01431 · Cited by 31
“Cell free virus are taken up by pDCs through endocytosis mediated by envelope–CD4 interaction (23, 24), while cell-associated virus enter pDCs by fusion or endocytosis (14).”
BackgroundSAMHD1 Degradation Enhances Active Suppression of Dendritic Cell Maturation by HIV-1
Hertoghs, N., van der Aar, A. M. G., Setiawan, L. C., Kootstra, N. A., Gringhuis, S. I., & Geijtenbeek, T. B. H. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1403016 · Cited by 34
“We preincubated DCs with a VLP that harbors the SIV-originated accessory protein Vpx, which degrades SAMHD1 (30, 45).”
MethodVpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells
Roesch, F., Richard, L., Rua, R., Porrot, F., Casartelli, N., & Schwartz, O. (2015) · Journal of Virology · doi:10.1128/jvi.02098-15 · Cited by 35
“and HIV-2 Vpx, by degrading SAMHD1 (15, 16), promotes infec-”
BackgroundStein, J. M., Bonsmann, M. S. G., & Streeck, H. (2016) · HLA · doi:10.1111/tan.12867 · Cited by 36
“It has been demonstrated that Vpx can block the host restriction factor SAMHD1, which in HIV-1 prevents the reverse transcription of viral genomes through depletion of intracellular dNTPs (40, 41).”
BackgroundIncreased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease
Kumari, N., Ammosova, T., Diaz, S. F., Lin, X., Niu, X., Ivanov, A. I., Jerebtsova, M., Dhawan, S., Oneal, P. A., & Nekhai, S. A. (2016) · Blood Advances · doi:10.1182/bloodadvances.2016000745 · Cited by 32
“Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease Namita Kumari,1 Tatiana Ammosova,1,2 Sharmin Diaz,1 Xionghao Lin,1 Xiaomei Niu,1 Andrey Ivanov,1 Marina Jerebtsova,3 Subhash Dhawan,4 Patricia Oneal,1,2 and Sergei Nekhai1-3 1Center for Sickle Cell Disease, 2Department o…”
BackgroundInfluentialCellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses
Becker, T., Le‐Trilling, V. T. K., & Trilling, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071636 · Cited by 30
“Well-known examples of viral exploitation of DDB1 and/or CRLs include the hepatitis B virus (HBV) protein HBx [84, [89] [90] [91] [92] , the HIV-1-and HIV-2-encoded protein Vpr [93] [94] [95] [96] [97] [98] [99] [100] [101] [102] , HIV-2 Vpx [103] [104] [105] [106] [107] [108] [109] , parainfluenza virus (PIV) V prote…”
SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts
Wichit, S., Hamel, R., Zanzoni, A., Diop, F., Cribier, A., Talignani, L., Diack, A., Ferraris, P., Liégeois, F., Urbach, S., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071695 · Cited by 33
Perez‐Zsolt, D., Martínez‐Picado, J., & Izquierdo‐Useros, N. (2019) · Viruses · doi:10.3390/v12010008 · Cited by 32
“In contrast to HIV-1, HIV-2 naturally replicates on DCs [98] , which depends on the counteraction of SAMHD1 by the viral antagonist Vpx [91] [92] [93] [94] [95] [96] [97] [98] [99] [100] [101] (Figure 2A, bottom) .”
BackgroundJohnson, J. R., Crosby, D. C., Hultquist, J. F., Kurland, A. P., Adhikary, P., Li, D., Marlett, J. M., Swann, J., Hüttenhain, R., Verschueren, E., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110690 · Cited by 31
Laplana, M., Carúz, A., Pineda, J. A., Puig, T., & Fibla, J. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis685 · Cited by 30
“and the newly described SAMHD1 [14, 15].”
The Cytoplasmic Tail of Retroviral Envelope Glycoproteins
Tedbury, P. R., & Freed, E. O. (2014) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2014.10.009 · Cited by 31
Tao, R. N., Fang, L., Bai, D., Ke, W., Zhou, Y., Wang, D., & Xiao, S. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701773 · Cited by 33
“target SAMHD1 for proteasomal degradation (28)].”
Guney, M. H., Nagalekshmi, K., McCauley, S. M., Carbone, C., Aydemir, Ö., & Luban, J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2404349121 · Cited by 28
“The Vpx-containing SIV-VLPs were added to these cultures to overcome a SAMHD1 block to lentiviral transduction (117, 118).”
Viral Live‐Attenuated Vaccines (LAVs): Past and Future Directions
Tang, Y., Li, Y., Cai, X., & Yin, X. (2024) · Advanced Science · doi:10.1002/advs.202407241 · Cited by 31
HIV Vpu Interferes with NF-κB Activity but Not with Interferon Regulatory Factor 3
Manganaro, L., de Castro, E., Maestre, A. M., Olivieri, K. C., García‐Sastre, A., Fernández-Sesma, A., & Simon, V. R. (2015) · Journal of Virology · doi:10.1128/jvi.01596-15 · Cited by 32
Adaptation to the Interferon-Induced Antiviral State by Human and Simian Immunodeficiency Viruses
Bitzegeio, J., Sampias, M., Bieniasz, P. D., & Hatziioannou, T. (2013) · Journal of Virology · doi:10.1128/jvi.03219-12 · Cited by 32
“Vpx proteins, delivered to target cells as a component of virions, can interact with SAMHD1 and target it for proteasomal degradation, thereby alleviating restriction (45, 46).”
BackgroundHeterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors
Mamede, J. I., Sitbon, M., Battini, J., & Courgnaud, V. (2013) · Retrovirology · doi:10.1186/1742-4690-10-77 · Cited by 32
“Lim ES, Fregoso OI, McCoy CO, Matsen FA, Malik HS, Emerman M: The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. Cell Host Microbe 2012, 11:194–204.”
InfluentialIdentification and characterization of naturally occurring splice variants of SAMHD1
Welbourn, S., Miyagi, E., White, T. E., Diaz‐Griffero, F., & Strebel, K. (2012) · Retrovirology · doi:10.1186/1742-4690-9-86 · Cited by 30
“Vpx has been shown to render monocytic cells permissive to HIV-1 infection by binding to and causing the proteosomal degradation of SAMHD1 [10,11].”
BackgroundResultMetabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages
Hollenbaugh, J. A., Montero, C. M., Schinazi, R. F., Munger, J. C., & Kim, B. (2016) · Virology · doi:10.1016/j.virol.2016.01.023 · Cited by 32
“…are exposed to Vpx from HIV-2 strains or virus-like particles (VLPs), cellular dNTP levels increased due to the elimination of SAMHD1 protein in non-dividing cells and resting CD4 + T cells (Baldauf et al., 2012; Hrecka et al., 2011; Kim et al., 2012; Laguette et al., 2011; Lahouassa et al., 2012).”
InfluentialKodigepalli, K. M., Li, M., Liu, S., & Wu, L. J. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1261226 · Cited by 30
Are Evolution and the Intracellular Innate Immune System Key Determinants in HIV Transmission?
Sumner, R. P., Thorne, L., Fink, D., Khan, H., Milne, R. S. B., & Towers, G. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01246 · Cited by 28
“org October 2017 | Volume 8 | Article 1246 factor targeted by the SIV accessory protein Vpx in myeloid cells (123, 124).”
BackgroundDong, H., Zhou, L., Ge, X., Guo, X., Han, J., & Yang, H. (2018) · Veterinary Microbiology · doi:10.1016/j.vetmic.2018.08.012 · Cited by 30
Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages
Siddiqui, R., Suzu, S., Ueno, M., Nasser, H., Koba, R., Bhuyan, F., Noyori, O., Hamidi, S., Sheng, G., Yasuda-Inoue, M., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007372 · Cited by 31
A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis
Wing, P. A. C., Davenne, T., Wettengel, J. M., Lai, A. G., Zhuang, X., Chakraborty, A., D’Arienzo, V., Kramer, C., Ko, C., Harris, J. M., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900355 · Cited by 29
“…triphosphate (dNTP) triphosphohydrolase (Goldstone et al, 2011; Powell et al, 2011) that restricts HIV-1 infection of myeloid cells and CD4 + T cells by depleting dNTPs required for reverse transcription (Hrecka et al, 2011; Laguette et al, 2011; Baldauf et al, 2012; Lahouassa et al, 2012).”
ISG15 Deficiency Enhances HIV-1 Infection by Accumulating Misfolded p53
Kuffour, E. O., König, R., Häussinger, D., Schulz, W. A., & Münk, C. (2019) · mBio · doi:10.1128/mbio.01342-19 · Cited by 31
Husain, A., Xu, J., Fujii, H., Nakata, M., Kobayashi, M., Wang, J. O., Rehwinkel, J., Honjo, T., & Begum, N. A. (2020) · The EMBO Journal · doi:10.15252/embj.2019102931 · Cited by 29
“…of SAMHD1, a dNTP triphosphohydrolase, restricts viral infection, particularly in non-dividing cells, by depleting cellular dNTPs which are essential for viral reverse transcription as well as replication (Hrecka et al , 2011; Laguette et al , 2011; Baldauf et al , 2012; Lahouassa et al , 2012).”
Role of Siglecs in viral infections: A double-edged sword interaction
Regué, D. R., Resa‐Infante, P., Gallemí, M., Laguía, F., Muñiz-Trabudua, X., Muñoz‐Basagoiti, J., Perez‐Zsolt, D., Chojnacki, J., Benet, S., Clotet, B., et al. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101113 · Cited by 30
Macrophages: Key Cellular Players in HIV Infection and Pathogenesis
Woottum, M., Yan, S., Sayettat, S., Grinberg, S., Cathelin, D., Bekaddour, N., Herbeuval, J., & Bénichou, S. (2024) · Viruses · doi:10.3390/v16020288 · Cited by 39
“…of SAMHD1 by the proteasome machinery allowing for the e ffi cient replication of these lentiviruses in myeloid cells [138,139]. and some SIVs leads to the degradation of SAMHD1 by the proteasome machinery allowing for the efficient replication of these lentiviruses in myeloid cells [138,139].”
BackgroundDeLucia, M., Mehrens, J., Wu, Y. G., & Ahn, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.469007 · Cited by 32
“Vpx has been demonstrated to reprogram the CRL4 E3 ubiquitin ligase by binding DCAF1, a substrate receptor of the ligase (35–37), and recruiting SAMHD1 for proteasome-dependent degradation (2, 3, 20).”
BackgroundAntagonism of SAMHD1 is actively maintained in natural infections of simian immunodeficiency virus
Spragg, C. J., & Emerman, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316839110 · Cited by 31
Type I IFN – A blunt spear in fighting HIV-1 infection
Acchioni, C., Marsili, G., Perrotti, E., Remoli, A. L., Sgarbanti, M., & Battistini, A. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.10.004 · Cited by 33
“Overcoming the SAMHD1mediated restriction by artificial addition of Vpx, [25,26] actually”
BackgroundBlanchet, F. P., Stalder, R., Czubala, M. A., Lehmann, M., Rio, L. M., Mangeat, B., & Piguet, V. (2013) · Retrovirology · doi:10.1186/1742-4690-10-6 · Cited by 33
“ing SAMHD1 [6,7] and members from the APOBEC3 protein family [8-11] as well as other restriction factors that remain undefined [12,13] can inhibit HIV-1 in the early stages of entry and replication within DC.”
BackgroundMethodInfluentialSAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
Ordonez, P., Kunzelmann, S., Groom, H. C. T., Yap, M. W., Weising, S., Meier, C., Bishop, K. N., Taylor, I. A., & Stoye, J. P. (2017) · Scientific Reports · doi:10.1038/srep42824 · Cited by 29
SAMHD1 deficient human monocytes autonomously trigger type I interferon
Martínez‐López, A., Martín-Fernández, M., Buta, S., Kim, B., Bogunovic, D., & Diaz‐Griffero, F. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.08.005 · Cited by 30
“The sterile alpha motif HD domain 1 (SAMHD1) protein is best known as potently restricting HIV-1 infection of non-cycling cells such as macrophages, dendritic cells and resting CD4 T cells (Arfi et al., 2008; Baldauf et al., 2012; Descours et al., 2012; Goujon et al., 2008, 2003; Goujon et al., 2007; Hrecka et al., 20…”
Guo, H., Wei, W., Wei, Z., Liu, X., Evans, S. L., Yang, W., Wang, H., Guo, Y., Zhao, K., Zhou, J.-Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066201 · Cited by 31
N -Linked Glycosylation Protects Gammaretroviruses against Deamination by APOBEC3 Proteins
Gerpe, M. C. R., Renner, T. M., Bélanger, K., Lam, C., Aydin, H., & Langlois, M. (2014) · Journal of Virology · doi:10.1128/jvi.03330-14 · Cited by 29
“(6, 7), SAMHD1 is defeated by Vpx (8, 9), A3 (A3F, A3G, A3D,”
Gelais, C. S., Kim, S. H., Ding, L., Yount, J. S., Ivanov, D. N., Spearman, P. W., & Wu, L. J. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.753947 · Cited by 32
“SAMHD1 has been characterized as a viral restriction factor that blocks the replication of several retroviruses, including HIV-1, and DNA viruses in quiescent cells such as resting T cells, macrophages, and dendritic cells (2, 3, 11, 12).”
BackgroundOu, C., Wang, Q., Zhang, Y., Kong, W., Zhang, S., Yu, Y. P., Ma, J., Liu, X., & Kong, X. (2017) · Virology Journal · doi:10.1186/s12985-017-0757-x · Cited by 28
HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages
Akiyama, H., & Gummuluru, S. (2020) · Viruses · doi:10.3390/v12070711 · Cited by 30
Advancing cellular immunotherapy with macrophages
Mishra, A., & Malonia, S. K. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121857 · Cited by 29
de Silva, S., Planelles, V., & Wu, L. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035385 · Cited by 30
“The recent discovery of SAMHD1 as a cellular restriction factor of HIV-1 in myeloid cells provides evidence for such a notion [48,49].”
BackgroundInfluentialRamirez, P. W., DePaula-Silva, A. B., Szaniawski, M. A., Barker, E., Bosque, A., & Planelles, V. (2015) · Retrovirology · doi:10.1186/s12977-015-0192-2 · Cited by 29
“Similarly, the HIV-2 accessory protein Vpx relies on a CRL4 complex to degrade the restriction factor SAMHD1 [6, 7].”
BackgroundSafeguard against DNA sensing: the role of TREX1 in HIV-1 infection and autoimmune diseases
Hasan, M., & Yan, N. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00193 · Cited by 34
Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism
Gnirß, K., Fiedler, M., Krämer-Kühl, A., Bolduan, S., Mittler, E., Becker, S., Schindler, M., & Pöhlmann, S. (2014) · Viruses · doi:10.3390/v6041654 · Cited by 30
“Single restriction factors have been identified by screening approaches seeking to determine the molecular mechanism underlying a specific antiviral activity [3] [4] [5] [6] [7] .”
BackgroundWang, H., Guo, H., Su, J., Rui, Y., Zheng, W., Gao, W., Zhang, W., Li, Z., Liu, G., Markham, R. B., et al. (2017) · Journal of Virology · doi:10.1128/jvi.00225-17 · Cited by 29
HIV-1 Vpr and p21 restrict LINE-1 mobility
Kawano, K., Doucet, A. J., Ueno, M., Kariya, R., An, W., Marzetta, F., Kuroki, M., Turelli, P., Sukegawa, S., Okada, S., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky688 · Cited by 28
Gelais, C. S., Coleman, C. M., Wang, J., & Wu, L. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034521 · Cited by 29
“Nef-mediated suppression of T cell activation is a critical feature of non-pathogenic primate lentiviruses and HIV-2, whereas HIV- 1 Nef induces T cell activation and contributes to viral pathogenicity [54].”
BackgroundSAMHD1 Limits HIV-1 Antigen Presentation by Monocyte-Derived Dendritic Cells
Ayinde, D., Bruel, T., Cardinaud, S., Porrot, F., Prado, J. G., Moris, A., & Schwartz, O. (2015) · Journal of Virology · doi:10.1128/jvi.00069-15 · Cited by 36
Hou, L., Zhao, J., Gao, S., Ji, T., Song, T., Li, Y., Wang, J., Geng, C., Long, M., Chen, J., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau7130 · Cited by 32
Nazitto, R., Amon, L. M., Mast, F. D., Aitchison, J. D., Aderem, A. A., Johnson, J. S., & Diercks, A. H. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001235 · Cited by 29
Examination of the APOBEC3 Barrier to Cross Species Transmission of Primate Lentiviruses
Gaba, A., Flath, B., & Chelico, L. (2021) · Viruses · doi:10.3390/v13061084 · Cited by 29
“suppressed by Vpx which is produced from HIV-2 and SIV, but not HIV-1 [18,19].”
BackgroundViral Modulation of the DNA Damage Response and Innate Immunity: Two Sides of the Same Coin
Lopez, A., Doyle, R. N., Sandoval, C., Nisson, K., Yang, V. B., & Fregoso, O. I. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167327 · Cited by 31
Efficient delivery of lentiviral vectors into resting human CD4 T cells
Geng, X., Doitsh, G., Yang, Z., Galloway, N. L. K., & Greene, W. C. (2014) · Gene Therapy · doi:10.1038/gt.2014.5 · Cited by 28
New insights into an X-traordinary viral protein
Schaller, T., Bauby, H., Hué, S., Malim, M. H., & Goujon, C. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00126 · Cited by 31
“Both studies showed that HIV-2/SIVmac Vpx induced SAMHD1 proteasomal degradation (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundDYRK1A Controls HIV-1 Replication at a Transcriptional Level in an NFAT Dependent Manner
Booiman, T., Loukachov, V. V., van Dort, K. A., Wout, A. B. V. ’., & Kootstra, N. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144229 · Cited by 28
“On the other hand, a number of host factors, such as MX2 [10–12], TRIM5α [13,14], SAMHD1 [15,16], APOBEC3 [17–19] and Tetherin [20] have been described to display antiviral effects and restrict viral replication.”
BackgroundLentiviral vector interactions with the host cell
Borsotti, C., Borroni, E., & Follenzi, A. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.08.016 · Cited by 29
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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