Restriction of diverse retroviruses by SAMHD1

Retrovirology

Nathaniel R Landau⁴  Dirk Lindemann³  Baek Kim²  Henning Hofmann⁴  Waaqo Daddacha²  Erik Müllers³  Sabine Wittmann¹  Nicolin Bloch⁴  Tanja Kahle¹  Thomas Gramberg¹ 

[1] Virologisches Institut, Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany;Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA;Institut für Virologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany;Microbiology Department, New York University School of Medicine, New York, USA

关键词: Accessory proteins;    Dendritic cells;    Vpx;    Macrophages;    SAMHD1;    HIV;   

Others  :  1209153
DOI  :  10.1186/1742-4690-10-26

 received in 2012-09-14, accepted in 2013-02-21,  发布年份 2013

【 摘 要 】

Background

SAMHD1 is a triphosphohydrolase that restricts the replication of HIV-1 and SIV in myeloid cells. In macrophages and dendritic cells, SAMHD1 restricts virus replication by diminishing the deoxynucleotide triphosphate pool to a level below that which supports lentiviral reverse transcription. HIV-2 and related SIVs encode the accessory protein Vpx to induce the proteasomal degradation of SAMHD1 following virus entry. While SAMHD1 has been shown to restrict HIV-1 and SIV, the breadth of its restriction is not known and whether other viruses have a means to counteract the restriction has not been determined.

Results

We show that SAMHD1 restricts a wide array of divergent retroviruses, including the alpha, beta and gamma classes. Murine leukemia virus was restricted by SAMHD1 in macrophages yet removal of SAMHD1 did not alleviate the block to infection because of an additional block to viral nuclear import. Prototype foamy virus (PFV) and Human T cell leukemia virus type I (HTLV-1) were the only retroviruses tested that were not restricted by SAMHD1. PFV reverse transcribes predominantly prior to entry and thus is unaffected by the dNTP level in the target cell. It is possible that HTLV-1 has a mechanism to render the virus resistant to SAMHD1-mediated restriction.

Conclusion

The results suggest that SAMHD1 has broad anti-retroviral activity against which most viruses have not found an escape.

【 授权许可】

   
2013 Gramberg et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 5.

【 参考文献 】

• [1]Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J: Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 2011, 474:658-661.
• [2]Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M: SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011, 474:654-657.
• [3]Laguette N, Rahm N, Sobhian B, Chable-Bessia C, Munch J, Snoeck J, Sauter D, Switzer WM, Heneine W, Kirchhoff F: Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein. Cell Host Microbe 2012, 11:205-217.
• [4]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.
• [5]Berger A, Sommer AF, Zwarg J, Hamdorf M, Welzel K, Esly N, Panitz S, Reuter A, Ramos I, Jatiani A: SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutieres syndrome are highly susceptible to HIV-1 infection. PLoS Pathog 2011, 7:e1002425.
• [6]Aravind L, Koonin EV: The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Trends Biochem Sci 1998, 23:469-472.
• [7]Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW: HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 2011, 480:379-382.
• [8]Powell RD, Holland PJ, Hollis T, Perrino FW: Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase. J Biol Chem 2011, 286:43596-43600.
• [9]Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T: SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 2012, 13:223-228.
• [10]Accola MA, Bukovsky AA, Jones MS, Gottlinger HG: A conserved dileucine-containing motif in p6(gag) governs the particle association of Vpx and Vpr of simian immunodeficiency viruses SIV(mac) and SIV(agm). J Virol 1999, 73:9992-9999.
• [11]Le Rouzic E, Belaidouni N, Estrabaud E, Morel M, Rain JC, Transy C, Margottin-Goguet F: HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle 2007, 6:182-188.
• [12]Srivastava S, Swanson SK, Manel N, Florens L, Washburn MP, Skowronski J: Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog 2008, 4:e1000059.
• [13]Sharova N, Wu Y, Zhu X, Stranska R, Kaushik R, Sharkey M, Stevenson M: Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 2008, 4:e1000057.
• [14]Goujon C, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A: With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC). Gene Ther 2006, 13:991-994.
• [15]Goujon C, Riviere L, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A: SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells. Retrovirology 2007, 4:2. BioMed Central Full Text
• [16]Gramberg T, Sunseri N, Landau NR: Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx. J Virol 2010, 84:1387-1396.
• [17]Sunseri N, O’Brien M, Bhardwaj N, Landau NR: Human immunodeficiency virus type 1 modified to package simian immunodeficiency virus Vpx efficiently infects macrophages and dendritic cells. J Virol 2011, 85:6263-6274.
• [18]Goujon C, Arfi V, Pertel T, Luban J, Lienard J, Rigal D, Darlix JL, Cimarelli A: Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells. J Virol 2008, 82:12335-12345.
• [19]Li F, Puffer BA, Montelaro RC: The S2 gene of equine infectious anemia virus is dispensable for viral replication in vitro. J Virol 1998, 72:8344-8348.
• [20]Yoon S, Kingsman SM, Kingsman AJ, Wilson SA, Mitrophanous KA: Characterization of the equine infectious anaemia virus S2 protein. J Gen Virol 2000, 81:2189-2194.
• [21]Munk C, Beck T, Zielonka J, Hotz-Wagenblatt A, Chareza S, Battenberg M, Thielebein J, Cichutek K, Bravo IG, O’Brien SJ: Functions, structure, and read-through alternative splicing of feline APOBEC3 genes. Genome Biol 2008, 9:R48. BioMed Central Full Text
• [22]Stern MA, Hu C, Saenz DT, Fadel HJ, Sims O, Peretz M, Poeschla EM: Productive replication of Vif-chimeric HIV-1 in feline cells. J Virol 2010, 84:7378-7395.
• [23]de Parseval A, Elder JH: Demonstration that orf2 encodes the feline immunodeficiency virus transactivating (Tat) protein and characterization of a unique gene product with partial rev activity. J Virol 1999, 73:608-617.
• [24]Sparger EE, Shacklett BL, Renshaw-Gegg L, Barry PA, Pedersen NC, Elder JH, Luciw PA: Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. Virology 1992, 187:165-177.
• [25]Adachi A, Sakai H, Tokunaga K, Kawamura M: Functional analysis of human spuma retrovirus genome. Virus Genes 1995, 11:15-20.
• [26]Bieniasz PD, Weiss RA, McClure MO: Cell cycle dependence of foamy retrovirus infection. J Virol 1995, 69:7295-7299.
• [27]Yu SF, Baldwin DN, Gwynn SR, Yendapalli S, Linial ML: Human foamy virus replication: a pathway distinct from that of retroviruses and hepadnaviruses. Science 1996, 271:1579-1582.
• [28]Takeuchi H, Takahashi M, Norose Y, Takeshita T, Fukunaga Y, Takahashi H: Transformation of breast milk macrophages by HTLV-I: implications for HTLV-I transmission via breastfeeding. Biomed Res 2010, 31:53-61.
• [29]Mazurov D, Ilinskaya A, Heidecker G, Lloyd P, Derse D: Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors. PLoS Pathog 2010, 6:e1000788.
• [30]White TE, Brandariz-Nunez A, Carlos Valle-Casuso J, Amie S, Nguyen L, Kim B, Brojatsch J, Diaz-Griffero F: Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. Virology 2013, 436:81-90.
• [31]Edwards D, Fenizia C, Gold H, de Castro-Amarante MF, Buchmann C, Pise-Masison CA, Franchini G: Orf-I and orf-II-encoded proteins in HTLV-1 infection and persistence. Viruses 2011, 3:861-885.
• [32]Kaushik R, Zhu X, Stranska R, Wu Y, Stevenson M: A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection. Cell Host Microbe 2009, 6:68-80.
• [33]Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR: A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 2010, 467:214-217.
• [34]Hofmann H, Logue EC, Bloch N, Daddacha W, Polsky SB, Schultz ML, Kim B, Landau NR: The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus. J Virol 2012, 86:12552-12560.
• [35]Connor RI, Chen BK, Choe S, Landau NR: Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 1995, 206:935-944.
• [36]Duda A, Stange A, Luftenegger D, Stanke N, Westphal D, Pietschmann T, Eastman SW, Linial ML, Rethwilm A, Lindemann D: Prototype foamy virus envelope glycoprotein leader peptide processing is mediated by a furin-like cellular protease, but cleavage is not essential for viral infectivity. J Virol 2004, 78:13865-13870.
• [37]Pietschmann T, Heinkelein M, Heldmann M, Zentgraf H, Rethwilm A, Lindemann D: Foamy virus capsids require the cognate envelope protein for particle export. J Virol 1999, 73:2613-2621.
• [38]Barraza RA, Poeschla EM: Human gene therapy vectors derived from feline lentiviruses. Vet Immunol Immunopathol 2008, 123:23-31.
• [39]Khare PD, Loewen N, Teo W, Barraza RA, Saenz DT, Johnson DH, Poeschla EM: Durable, safe, multi-gene lentiviral vector expression in feline trabecular meshwork. Mol Ther 2008, 16:97-106.
• [40]Suerth JD, Maetzig T, Galla M, Baum C, Schambach A: Self-inactivating alpharetroviral vectors with a split-packaging design. J Virol 2010, 84:6626-6635.
• [41]Newman RM, Hall L, Connole M, Chen GL, Sato S, Yuste E, Diehl W, Hunter E, Kaur A, Miller GM, Johnson WE: Balancing selection and the evolution of functional polymorphism in old world monkey TRIM5alpha. Proc Natl Acad Sci U S A 2006, 103:19134-19139.
• [42]Stansell E, Apkarian R, Haubova S, Diehl WE, Tytler EM, Hunter E: Basic residues in the Mason-Pfizer monkey virus gag matrix domain regulate intracellular trafficking and capsid-membrane interactions. J Virol 2007, 81:8977-8988.
• [43]McKay T, Patel M, Pickles RJ, Johnson LG, Olsen JC: Influenza M2 envelope protein augments avian influenza hemagglutinin pseudotyping of lentiviral vectors. Gene Ther 2006, 13:715-724.
• [44]Munk C, Brandt SM, Lucero G, Landau NR: A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc Natl Acad Sci U S A 2002, 99:13843-13848.
• [45]Mullers E, Uhlig T, Stirnnagel K, Fiebig U, Zentgraf H, Lindemann D: Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis. J Virol 2011, 85:1452-1463.
• [46]Diamond TL, Roshal M, Jamburuthugoda VK, Reynolds HM, Merriam AR, Lee KY, Balakrishnan M, Bambara RA, Planelles V, Dewhurst S, Kim B: Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem 2004, 279:51545-51553.