DIAZ-GRIFFERO LAB WEBSITE

HIV-1 REVERSE TRANSCRIPTION AND UNCOATING

Our laboratory is interested on understanding the mechanism used by restriction factors (endogenously expressed proteins) to restrict HIV-1 replication. The restriction factors TRIM5alpha and TRIMCyp are monkey proteins that potently block HIV-1 during uncoating, which is the initial step of HIV-1 replication. Our investigations have demonstrated that TRIM5 proteins block HIV-1 replication by inhibiting reverse transcription--essential early step in HIV-1 replication that converts viral RNA into viral DNA. We are using these restriction factors to carefully define the uncoating mechanism of HIV-1, which will give rise to new ways to inhibit HIV-1 replication and treat HIV-1/AIDS. We have established that these restrictions factors accelerate uncoating making HIV-1 replication abortive. Our investigations will attempt to mechanistically define the timing of uncoating and reverse transcription during replication. Interestingly but not surprisingly these restriction factors block HIV-1 replication extremely potently and better than any drug known to date. These restriction factors were design by nature to block HIV-1 replication, and nature knows best. We currently have in vivo and vitro assays to follow the uncoating and reverse transcription of HIV-1. These assays had allowed us to better understand how reverse transcription is blocked during the accelerated uncoating triggered by TRIM5alpha and TRIMCyp. We are also studying the structural biology of these restriction factors attempting to identify the TRIM5alpha domains required to block HIV-1 replication. We have also created mice strains that do not contain TRIM5alpha to understand the in vivo role of TRIM5alpha. 

To understand uncoating in a broader manner, we are also studying the molecule transportin-3 (TNPO3) known to be required for HIV-1 replication during the initial steps of HIV-1 replication. We are identifying which proteins of the HIV-1 virus is required to interact with TNPO3, which is a nuclear transporter. We think that this transporter promotes HIV-1 uncoating and assist the transport of HIV-1 into the nucleus of the cells allowing productive infection. We have also created mice strains that do not express transporting to better understand the role of TNPO3 in HIV-1 replication using and in vivo model.

HIV-1 NUCLEAR IMPORT

Over the years, we have defined the nucleopore component proteins that are important for HIV-1 nuclear import. Among them, we showed that Nup153 and RANBP2 directly interact with the HIV-1 core, and are essential proteins for importing the HIV-1 replication machinery into the nucleus. HIV-1 reverse transcription (RT) occurs before or during uncoating, but the cellular compartment where RT and uncoating occurs is unknown. Using imaging and biochemical assays to track HIV-1 capsids in the nucleus during infection, we demonstrated that higher-order capsid complexes and/or complete cores containing the viral genome are imported into the nucleus. Inhibition of RT does not prevent capsid nuclear import; thus, RT may occur in nuclear compartments. Cytosolic and nuclear fractions of infected cells reveal that most RT intermediates are enriched in nuclear fractions, suggesting that HIV-1 RT occurs in the nucleus alongside uncoating.Thus, nuclear import precedes RT and uncoating, which fundamentally changes our understanding of HIV-1 infection.

HIV-1 INTRANUCLEAR EVENTS

After the viral DNA is synthesized in the nucleus, a process known as integration occurs, which is the incorporation of viral DNA in the cellular DNA. Recently, we found that capsid in the nucleus induces recruitment of cleavage and polyadenylation specific factor 6 (CPSF6) to SC35 nuclear speckles, which are highly active transcription sites, suggesting that CPSF6 through capsid is recruiting viral complexes to SC35 speckles for the occurrence of RT. This suggests that molecules like CPSF6 maybe involved in localizing the virus to specific places in the cell. The HIV-1 events inside the nucleus are intensely investigated in our lab. 

Finally, we are studying HIV-1 infected patients known as elite controllers (ECs), which are defined as HIV-1 infected individuals that never develop AIDS. We strongly believe that these individuals have novel ways to restrict HIV-1 replication, which will help us to develop new therapies against HIV-1/AIDS. Among this novel ways to restrict HIV-1 replication, we hypothesize the existence of new restriction factors in T cells that block HIV-1 replication. For this purpose, we are currently investigating HIV-1 replication blocks in T cells. We have several T cell lines that block HIV-1 replication at early stages suggesting the existence of a block similar to the one imposed by TRIM5alpha to HIV-1 replication.

1.         Selyutina A, Hu P, Miller S, Simons LM, Yu HJ, Hultquist JF, Lee K, KewalRamani VN, Diaz-Griffero F. GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors. iScience. 2022;25(1):103593. Epub 2022/01/11. doi: 10.1016/j.isci.2021.103593. PubMed PMID: 35005542; PMCID: PMC8718827.

2.         Yu CH, Bhattacharya A, Persaud M, Taylor AB, Wang Z, Bulnes-Ramos A, Xu J, Selyutina A, Martinez-Lopez A, Cano K, Demeler B, Kim B, Hardies SC, Diaz-Griffero F, Ivanov DN. Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification. Nature communications. 2021;12(1):731. Epub 2021/02/04. doi: 10.1038/s41467-021-21023-8. PubMed PMID: 33531504.

3.         Selyutina A, Diaz-Griffero F. Biochemical detection of capsid in the nucleus during HIV-1 infection. STAR Protoc. 2021;2(1):100323. Epub 2021/02/20. doi: 10.1016/j.xpro.2021.100323. PubMed PMID: 33604582; PMCID: PMC7873705.

4.         Persaud M, Selyutina A, Buffone C, Opp S, Donahue DA, Schwartz O, Diaz-Griffero F. Nuclear restriction of HIV-1 infection by SUN1. Scientific reports. 2021;11(1):19128. Epub 2021/09/29. doi: 10.1038/s41598-021-98541-4. PubMed PMID: 34580332; PMCID: PMC8476499.

5.         Martinat C, Cormier A, Tobaly-Tapiero J, Palmic N, Casartelli N, Mahboubi B, Coggins SA, Buchrieser J, Persaud M, Diaz-Griffero F, Espert L, Bossis G, Lesage P, Schwartz O, Kim B, Margottin-Goguet F, Saib A, Zamborlini A. SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells. Nature communications. 2021;12(1):4582. Epub 2021/07/30. doi: 10.1038/s41467-021-24802-5. PubMed PMID: 34321470; PMCID: PMC8319325.

6.         Bowen NE, Temple J, Shepard C, Oo A, Arizaga F, Kapoor-Vazirani P, Persaud M, Yu CH, Kim DH, Schinazi RF, Ivanov DN, Diaz-Griffero F, Yu DS, Xiong Y, Kim B. Structural and functional characterization explains loss of dNTPase activity of the cancer-specific R366C/H mutant SAMHD1 proteins. J Biol Chem. 2021;297(4):101170. Epub 2021/09/08. doi: 10.1016/j.jbc.2021.101170. PubMed PMID: 34492268; PMCID: PMC8497992.

7.         Selyutina A, Persaud M, Simons LM, Bulnes-Ramos A, Buffone C, Martinez-Lopez A, Scoca V, Di Nunzio F, Hiatt J, Marson A, Krogan NJ, Hultquist JF, Diaz-Griffero F. Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Cell Rep. 2020;30(11):3766-77 e6. Epub 2020/03/19. doi: 10.1016/j.celrep.2020.02.100. PubMed PMID: 32187548.

8.         Selyutina A, Persaud M, Lee K, KewalRamani V, Diaz-Griffero F. Nuclear Import of the HIV-1 Core Precedes Reverse Transcription and Uncoating. Cell Rep. 2020;32(13):108201. Epub 2020/10/01. doi: 10.1016/j.celrep.2020.108201. PubMed PMID: 32997983.

9.         Martinez-Lopez A, Persaud M, Chavez MP, Zhang H, Rong L, Liu S, Wang TT, Sarafianos SG, Diaz-Griffero F. Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus. EBioMedicine. 2019;47:269-83. Epub 2019/09/11. doi: 10.1016/j.ebiom.2019.08.060. PubMed PMID: 31501074; PMCID: PMC6796538.

10.       Kim ET, Roche KL, Kulej K, Spruce LA, Seeholzer SH, Coen DM, Diaz-Griffero F, Murphy EA, Weitzman MD. SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-kappaB Activation. Cell Rep. 2019;28(2):434-48 e6. Epub 2019/07/11. doi: 10.1016/j.celrep.2019.06.027. PubMed PMID: 31291579.

11.       Imam S, Komurlu S, Mattick J, Selyutina A, Talley S, Eddins A, Diaz-Griffero F, Campbell EM. K63-Linked Ubiquitin Is Required for Restriction of HIV-1 Reverse Transcription and Capsid Destabilization by Rhesus TRIM5alpha. J Virol. 2019;93(14). Epub 2019/05/10. doi: 10.1128/JVI.00558-19. PubMed PMID: 31068426; PMCID: PMC6600202.

12.       Buffone C, Kutzner J, Opp S, Martinez-Lopez A, Selyutina A, Coggings SA, Studdard LR, Ding L, Kim B, Spearman P, Schaller T, Diaz-Griffero F. The ability of SAMHD1 to block HIV-1 but not SIV requires expression of MxB. Virology. 2019;531:260-8. Epub 2019/04/09. doi: 10.1016/j.virol.2019.03.018. PubMed PMID: 30959264; PMCID: PMC6487861.

13.       Wang Z, Bhattacharya A, White T, Buffone C, McCabe A, Nguyen LA, Shepard CN, Pardo S, Kim B, Weintraub ST, Demeler B, Diaz-Griffero F, Ivanov DN. Functionality of Redox-Active Cysteines Is Required for Restriction of Retroviral Replication by SAMHD1. Cell Rep. 2018;24(4):815-23. doi: 10.1016/j.celrep.2018.06.090. PubMed PMID: 30044979; PMCID: 6067006.

14.       Selyutina A, Bulnes-Ramos A, Diaz-Griffero F. Binding of host factors to stabilized HIV-1 capsid tubes. Virology. 2018;523:1-5. doi: 10.1016/j.virol.2018.07.019. PubMed PMID: 30056211; PMCID: PMC6135678.

15.       Schulte B, Selyutina A, Opp S, Herschhorn A, Sodroski JG, Pizzato M, Diaz-Griffero F. Localization to detergent-resistant membranes and HIV-1 core entry inhibition correlate with HIV-1 restriction by SERINC5. Virology. 2018;515:52-65. Epub 2017/12/22. doi: 10.1016/j.virol.2017.12.005. PubMed PMID: 29268082; PMCID: PMC5801005.

16.       Schott K, Fuchs NV, Derua R, Mahboubi B, Schnellbacher E, Seifried J, Tondera C, Schmitz H, Shepard C, Brandariz-Nunez A, Diaz-Griffero F, Reuter A, Kim B, Janssens V, Konig R. Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55alpha holoenzymes during mitotic exit. Nature communications. 2018;9(1):2227. doi: 10.1038/s41467-018-04671-1. PubMed PMID: 29884836; PMCID: 5993806.

17.       Said EA, Diaz-Griffero F, Bonte D, Lamarre D, Al-Jabri AA. Immune Responses to RNA Viruses. J Immunol Res. 2018;2018:5473678. Epub 2018/07/17. doi: 10.1155/2018/5473678. PubMed PMID: 30009187; PMCID: PMC6020492.

18.       Persaud M, Martinez-Lopez A, Buffone C, Porcelli SA, Diaz-Griffero F. Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH. Virology. 2018;518:301-12. Epub 2018/03/27. doi: 10.1016/j.virol.2018.03.009. PubMed PMID: 29574335.

19.       Meyerson NR, Warren CJ, Vieira D, Diaz-Griffero F, Sawyer SL. Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes. PLoS Pathog. 2018;14(4):e1006983. Epub 2018/04/04. doi: 10.1371/journal.ppat.1006983. PubMed PMID: 29614111; PMCID: PMC5882152.

20.       Martinez-Lopez A, Martin-Fernandez M, Buta S, Kim B, Bogunovic D, Diaz-Griffero F. SAMHD1 deficient human monocytes autonomously trigger type I interferon. Molecular immunology. 2018;101:450-60. doi: 10.1016/j.molimm.2018.08.005. PubMed PMID: 30099227.

21.       Manganaro L, Hong P, Hernandez MM, Argyle D, Mulder LCF, Potla U, Diaz-Griffero F, Lee B, Fernandez-Sesma A, Simon V. IL-15 regulates susceptibility of CD4(+) T cells to HIV infection. Proc Natl Acad Sci U S A. 2018;115(41):E9659-E67. Epub 2018/09/28. doi: 10.1073/pnas.1806695115. PubMed PMID: 30257946; PMCID: PMC6187195.

22.       Buffone C, Martinez-Lopez A, Fricke T, Opp S, Severgnini M, Cifola I, Petiti L, Frabetti S, Skorupka K, Zadrozny KK, Ganser-Pornillos BK, Pornillos O, Di Nunzio F, Diaz-Griffero F. Nup153 Unlocks the Nuclear Pore Complex for HIV-1 Nuclear Translocation in Nondividing Cells. J Virol. 2018;92(19). Epub 2018/07/13. doi: 10.1128/JVI.00648-18. PubMed PMID: 29997211; PMCID: PMC6146805.

23.       White TE, Brandariz-Nunez A, Martinez-Lopez A, Knowlton C, Lenzi G, Kim B, Ivanov D, Diaz-Griffero F. A SAMHD1 mutation associated with Aicardi-Goutieres syndrome uncouples the ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I interferon in humans. Hum Mutat. 2017;38(6):658-68. doi: 10.1002/humu.23201. PubMed PMID: 28229507; PMCID: 5738905.

24.       Opp S, Fricke T, Shepard C, Kovalskyy D, Bhattacharya A, Herkules F, Ivanov DN, Kim B, Valle-Casuso J, Diaz-Griffero F. The small-molecule 3G11 inhibits HIV-1 reverse transcription. Chem Biol Drug Des. 2017;89(4):608-18. Epub 2016/10/18. doi: 10.1111/cbdd.12886. PubMed PMID: 27748043; PMCID: PMC5378662.

25.       Fricke T, Brandariz-Nunez A, Wang X, Smith AB, 3rd, Diaz-Griffero F. Fricke et al., "Human Cytosolic Extracts Stabilize the HIV-1 Core". J Virol. 2017;91(24). Epub 2017/12/02. doi: 10.1128/JVI.01732-17. PubMed PMID: 29191990; PMCID: PMC5709579.

26.       Dharan A, Opp S, Abdel-Rahim O, Keceli SK, Imam S, Diaz-Griffero F, Campbell EM. Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. Proc Natl Acad Sci U S A. 2017;114(50):E10707-E16. Epub 2017/11/29. doi: 10.1073/pnas.1712033114. PubMed PMID: 29180435; PMCID: PMC5740630.

27.       White TE, Brandariz-Nunez A, Han K, Sawyer SL, Kim B, Diaz-Griffero F. Modulation of LINE-1 Retrotransposition by a Human SAMHD1 Polymorphism. Virology reports. 2016;6:53-60. doi: 10.1016/j.virep.2016.06.001. PubMed PMID: 27482511; PMCID: 4959807.

28.       Wang Z, Bhattacharya A, Villacorta J, Diaz-Griffero F, Ivanov DN. Allosteric Activation of SAMHD1 Protein by Deoxynucleotide Triphosphate (dNTP)-dependent Tetramerization Requires dNTP Concentrations That Are Similar to dNTP Concentrations Observed in Cycling T Cells. J Biol Chem. 2016;291(41):21407-13. doi: 10.1074/jbc.C116.751446. PubMed PMID: 27566548; PMCID: 5076810.

29.       Thenin-Houssier S, de Vera IM, Pedro-Rosa L, Brady A, Richard A, Konnick B, Opp S, Buffone C, Fuhrmann J, Kota S, Billack B, Pietka-Ottlik M, Tellinghuisen T, Choe H, Spicer T, Scampavia L, Diaz-Griffero F, Kojetin DJ, Valente ST. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. Antimicrob Agents Chemother. 2016;60(4):2195-208. Epub 2016/01/27. doi: 10.1128/AAC.02574-15. PubMed PMID: 26810656; PMCID: PMC4808204.

30.       Nepveu-Traversy ME, Demogines A, Fricke T, Plourde MB, Riopel K, Veillette M, Diaz-Griffero F, Sawyer SL, Berthoux L. A putative SUMO interacting motif in the B30.2/SPRY domain of rhesus macaque TRIM5alpha important for NF-kappaB/AP-1 signaling and HIV-1 restriction. Heliyon. 2016;2(1):e00056. Epub 2016/07/22. doi: 10.1016/j.heliyon.2015.e00056. PubMed PMID: 27441239; PMCID: PMC4945854.

31.       Fricke T, Diaz-Griffero F. HIV-1 Capsid Stabilization Assay. Methods Mol Biol. 2016;1354:39-47. Epub 2015/12/31. doi: 10.1007/978-1-4939-3046-3_3. PubMed PMID: 26714703; PMCID: PMC7906248.

32.       Donahue DA, Amraoui S, di Nunzio F, Kieffer C, Porrot F, Opp S, Diaz-Griffero F, Casartelli N, Schwartz O. SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV. J Virol. 2016;90(8):4199-214. doi: 10.1128/JVI.03202-15. PubMed PMID: 26865710; PMCID: 4810566.

33.       Chen NY, Zhou L, Gane PJ, Opp S, Ball NJ, Nicastro G, Zufferey M, Buffone C, Luban J, Selwood D, Diaz-Griffero F, Taylor I, Fassati A. HIV-1 capsid is involved in post-nuclear entry steps. Retrovirology. 2016;13:28. Epub 2016/04/25. doi: 10.1186/s12977-016-0262-0. PubMed PMID: 27107820; PMCID: PMC4842275.

34.       Campbell EM, Weingart J, Sette P, Opp S, Sastri J, O'Connor SK, Talley S, Diaz-Griffero F, Hirsch V, Bouamr F. TRIM5alpha-Mediated Ubiquitin Chain Conjugation Is Required for Inhibition of HIV-1 Reverse Transcription and Capsid Destabilization. J Virol. 2016;90(4):1849-57. Epub 2015/12/18. doi: 10.1128/JVI.01948-15. PubMed PMID: 26676782; PMCID: PMC4733990.

35.       Bhattacharya A, Wang Z, White T, Buffone C, Nguyen LA, Shepard CN, Kim B, Demeler B, Diaz-Griffero F, Ivanov DN. Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect. Scientific reports. 2016;6:31353. doi: 10.1038/srep31353. PubMed PMID: 27511536; PMCID: 4980677.

36.       Yudina Z, Roa A, Johnson R, Biris N, de Souza Aranha Vieira DA, Tsiperson V, Reszka N, Taylor AB, Hart PJ, Demeler B, Diaz-Griffero F, Ivanov DN. RING Dimerization Links Higher-Order Assembly of TRIM5alpha to Synthesis of K63-Linked Polyubiquitin. Cell Rep. 2015;12(5):788-97. doi: 10.1016/j.celrep.2015.06.072. PubMed PMID: 26212332; PMCID: 4526822.

37.       Schulte B, Buffone C, Opp S, Di Nunzio F, De Souza Aranha Vieira DA, Brandariz-Nunez A, Diaz-Griffero F. Restriction of HIV-1 Requires the N-Terminal Region of MxB as a Capsid-Binding Motif but Not as a Nuclear Localization Signal. J Virol. 2015;89(16):8599-610. doi: 10.1128/JVI.00753-15. PubMed PMID: 26063425; PMCID: 4524248.

38.       Posch W, Steger M, Knackmuss U, Blatzer M, Baldauf HM, Doppler W, White TE, Hortnagl P, Diaz-Griffero F, Lass-Florl C, Hackl H, Moris A, Keppler OT, Wilflingseder D. Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. PLoS Pathog. 2015;11(6):e1005005. doi: 10.1371/journal.ppat.1005005. PubMed PMID: 26121641; PMCID: 4485899.

39.       Opp S, Vieira DA, Schulte B, Chanda SK, Diaz-Griffero F. MxB Is Not Responsible for the Blocking of HIV-1 Infection Observed in Alpha Interferon-Treated Cells. J Virol. 2015;90(6):3056-64. Epub 2016/01/01. doi: 10.1128/JVI.03146-15. PubMed PMID: 26719253; PMCID: PMC4810631.

40.       Opp S, Vieira D, Schulte B, Chanda SK, Diaz-Griffero F. MxB is not responsible for the block to HIV-1 observed in IFN-alpha-treated cells. J Virol. 2015. doi: 10.1128/JVI.03146-15. PubMed PMID: 26719253.

41.       Malikov V, da Silva ES, Jovasevic V, Bennett G, de Souza Aranha Vieira DA, Schulte B, Diaz-Griffero F, Walsh D, Naghavi MH. HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus. Nature communications. 2015;6:6660. doi: 10.1038/ncomms7660. PubMed PMID: 25818806; PMCID: 4380233.

42.       Lelek M, Casartelli N, Pellin D, Rizzi E, Souque P, Severgnini M, Di Serio C, Fricke T, Diaz-Griffero F, Zimmer C, Charneau P, Di Nunzio F. Chromatin organization at the nuclear pore favours HIV replication. Nature communications. 2015;6:6483. doi: 10.1038/ncomms7483. PubMed PMID: 25744187; PMCID: 4366494.

43.       Buffone C, Schulte B, Opp S, Diaz-Griffero F. Contribution of MxB oligomerization to HIV-1 capsid binding and restriction. J Virol. 2015;89(6):3285-94. doi: 10.1128/JVI.03730-14. PubMed PMID: 25568212; PMCID: 4337540.

44.       Yang Y, Luban J, Diaz-Griffero F. The fate of HIV-1 capsid: a biochemical assay for HIV-1 uncoating. Methods Mol Biol. 2014;1087:29-36. doi: 10.1007/978-1-62703-670-2_3. PubMed PMID: 24158811; PMCID: 4317566.

45.       Yang Y, Brandariz-Nunez A, Fricke T, Ivanov DN, Sarnak Z, Diaz-Griffero F. Binding of the rhesus TRIM5alpha PRYSPRY domain to capsid is necessary but not sufficient for HIV-1 restriction. Virology. 2014;448:217-28. doi: 10.1016/j.virol.2013.10.012. PubMed PMID: 24314652; PMCID: 3900861.

46.       White TE, Brandariz-Nunez A, Valle-Casuso JC, Knowlton C, Kim B, Sawyer SL, Diaz-Griffero F. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility. Virology. 2014;460-461:34-44. doi: 10.1016/j.virol.2014.04.023. PubMed PMID: 25010268; PMCID: 4101048.

47.       St Gelais C, de Silva S, Hach JC, White TE, Diaz-Griffero F, Yount JS, Wu L. Identification of cellular proteins interacting with the retroviral restriction factor SAMHD1. J Virol. 2014;88(10):5834-44. doi: 10.1128/JVI.00155-14. PubMed PMID: 24623419; PMCID: 4019113.

48.       Sastri J, Johnsen L, Smolin N, Imam S, Mukherjee S, Lukic Z, Brandariz-Nunez A, Robia SL, Diaz-Griffero F, Wiethoff C, Campbell EM. Restriction of HIV-1 by rhesus TRIM5alpha is governed by alpha helices in the Linker2 region. J Virol. 2014;88(16):8911-23. doi: 10.1128/JVI.01134-14. PubMed PMID: 24872590; PMCID: 4136267.

49.       Ryoo J, Choi J, Oh C, Kim S, Seo M, Kim SY, Seo D, Kim J, White TE, Brandariz-Nunez A, Diaz-Griffero F, Yun CH, Hollenbaugh JA, Kim B, Baek D, Ahn K. The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nat Med. 2014;20(8):936-41. doi: 10.1038/nm.3626. PubMed PMID: 25038827.

50.       Lukic Z, Dharan A, Fricke T, Diaz-Griffero F, Campbell EM. HIV-1 uncoating is facilitated by dynein and kinesin 1. J Virol. 2014;88(23):13613-25. doi: 10.1128/JVI.02219-14. PubMed PMID: 25231297; PMCID: 4248982.

51.       Hollenbaugh JA, Tao S, Lenzi GM, Ryu S, Kim DH, Diaz-Griffero F, Schinazi RF, Kim B. dNTP pool modulation dynamics by SAMHD1 protein in monocyte-derived macrophages. Retrovirology. 2014;11:63. doi: 10.1186/s12977-014-0063-2. PubMed PMID: 25158827; PMCID: 4161909.

52.       Fricke T, White TE, Schulte B, de Souza Aranha Vieira DA, Dharan A, Campbell EM, Brandariz-Nunez A, Diaz-Griffero F. MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1. Retrovirology. 2014;11(1):68. doi: 10.1186/PREACCEPT-6453674081373986. PubMed PMID: 25123063; PMCID: 4145229.

53.       Fricke T, Buffone C, Opp S, Valle-Casuso J, Diaz-Griffero F. BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid. Retrovirology. 2014;11:120. doi: 10.1186/s12977-014-0120-x. PubMed PMID: 25496772; PMCID: 4271331.

54.       Brojatsch J, Lima H, Kar AK, Jacobson LS, Muehlbauer SM, Chandran K, Diaz-Griffero F. A proteolytic cascade controls lysosome rupture and necrotic cell death mediated by lysosome-destabilizing adjuvants. PLoS One. 2014;9(6):e95032. doi: 10.1371/journal.pone.0095032. PubMed PMID: 24893007; PMCID: 4043491.

55.       Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc Natl Acad Sci U S A. 2014;111(52):18625-30. doi: 10.1073/pnas.1419945112. PubMed PMID: 25518861; PMCID: 4284599.

56.       Yang Y, Fricke T, Diaz-Griffero F. Inhibition of reverse transcriptase activity increases stability of the HIV-1 core. J Virol. 2013;87(1):683-7. Epub 2012/10/19. doi: 10.1128/JVI.01228-12. PubMed PMID: 23077298; PMCID: PMC3536417.

57.       White TE, Brandariz-Nunez A, Valle-Casuso JC, Amie S, Nguyen LA, Kim B, Tuzova M, Diaz-Griffero F. The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation. Cell Host Microbe. 2013;13(4):441-51. Epub 2013/04/23. doi: S1931-3128(13)00115-7 [pii]

10.1016/j.chom.2013.03.005. PubMed PMID: 23601106.

58.       White TE, Brandariz-Nunez A, Valle-Casuso JC, 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(1):81-90. Epub 2012/11/20. doi: S0042-6822(12)00537-5 [pii]

10.1016/j.virol.2012.10.029. PubMed PMID: 23158101.

59.       Pham QT, Veillette M, Brandariz-Nunez A, Pawlica P, Thibert-Lefebvre C, Chandonnet N, Diaz-Griffero F, Berthoux L. A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Virus Res. 2013;173(2):306-14. Epub 2013/01/30. doi: S0168-1702(13)00014-2 [pii]

10.1016/j.virusres.2013.01.013. PubMed PMID: 23357295.

60.       Lima H, Jr., Jacobson LS, Goldberg MF, Chandran K, Diaz-Griffero F, Lisanti MP, Brojatsch J. Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle. 2013;12(12):1868-78. doi: 10.4161/cc.24903. PubMed PMID: 23708522; PMCID: 3735701.

61.       Kim ET, White TE, Brandariz-Nunez A, Diaz-Griffero F, Weitzman MD. SAMHD1 restricts herpes simplex virus 1 in macrophages by limiting DNA replication. J Virol. 2013;87(23):12949-56. doi: 10.1128/JVI.02291-13. PubMed PMID: 24067963; PMCID: 3838123.

62.       Jacobson LS, Lima H, Jr., Goldberg MF, Gocheva V, Tsiperson V, Sutterwala FS, Joyce JA, Gapp BV, Blomen VA, Chandran K, Brummelkamp TR, Diaz-Griffero F, Brojatsch J. Cathepsin-mediated necrosis controls the adaptive immune response by Th2 (T helper type 2)-associated adjuvants. J Biol Chem. 2013;288(11):7481-91. Epub 2013/01/09. doi: M112.400655 [pii]

10.1074/jbc.M112.400655. PubMed PMID: 23297415; PMCID: 3597789.

63.       Fricke T, Valle-Casuso JC, White TE, Brandariz-Nunez A, Bosche WJ, Reszka N, Gorelick R, Diaz-Griffero F. The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6. Retrovirology. 2013;10(1):46. Epub 2013/04/30. doi: 1742-4690-10-46 [pii]

10.1186/1742-4690-10-46. PubMed PMID: 23622145.

64.       Fricke T, Brandariz-Nunez A, Wang X, Smith AB, 3rd, Diaz-Griffero F. Human cytosolic extracts stabilize the HIV-1 core. J Virol. 2013;87(19):10587-97. doi: 10.1128/JVI.01705-13. PubMed PMID: 23885082; PMCID: 3807412.

65.       Fassler M, Weissberg I, Levy N, Diaz-Griffero F, Monsonego A, Friedman A, Taube R. Preferential lentiviral targeting of astrocytes in the central nervous system. PLoS One. 2013;8(10):e76092. doi: 10.1371/journal.pone.0076092. PubMed PMID: 24098426; PMCID: 3788778.

66.       Di Nunzio F, Fricke T, Miccio A, Valle-Casuso JC, Perez P, Souque P, Rizzi E, Severgnini M, Mavilio F, Charneau P, Diaz-Griffero F. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication. Virology. 2013;440(1):8-18. doi: 10.1016/j.virol.2013.02.008. PubMed PMID: 23523133; PMCID: 3860269.

67.       Brandariz-Nunez A, Valle-Casuso JC, White TE, Nguyen L, Bhattacharya A, Wang Z, Demeler B, Amie S, Knowlton C, Kim B, Ivanov DN, Diaz-Griffero F. Contribution of oligomerization to the anti-HIV-1 properties of SAMHD1. Retrovirology. 2013;10:131. doi: 10.1186/1742-4690-10-131. PubMed PMID: 24219908; PMCID: 3882887.

68.       Brandariz-Nunez A, Roa A, Valle-Casuso JC, Biris N, Ivanov D, Diaz-Griffero F. Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5alpha. Virology. 2013;435(2):463-71. doi: 10.1016/j.virol.2012.09.042. PubMed PMID: 23084420; PMCID: 3534947.

69.       Biris N, Tomashevski A, Bhattacharya A, Diaz-Griffero F, Ivanov DN. Rhesus monkey TRIM5alpha SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core. J Mol Biol. 2013;425(24):5032-44. doi: 10.1016/j.jmb.2013.07.025. PubMed PMID: 23886867; PMCID: 4116666.

70.       Welbourn S, Miyagi E, White TE, Diaz-Griffero F, Strebel K. Identification and characterization of naturally occurring splice variants of SAMHD1. Retrovirology. 2012;9:86. doi: 10.1186/1742-4690-9-86. PubMed PMID: 23092512; PMCID: 3503569.

71.       Valle-Casuso JC, Di Nunzio F, Yang Y, Reszka N, Lienlaf M, Arhel N, Perez P, Brass AL, Diaz-Griffero F. TNPO3 is Required for HIV-1 Replication After Nuclear Import but Prior to Integration and Binds the HIV-1 Core. J Virol. 2012. Epub 2012/03/09. doi: JVI.00451-12 [pii]

10.1128/JVI.00451-12. PubMed PMID: 22398280.

72.       Roa A, Hayashi F, Yang Y, Lienlaf M, Zhou J, Shi J, Watanabe S, Kigawa T, Yokoyama S, Aiken C, Diaz-Griffero F. RING domain mutations uncouple TRIM5alpha restriction of HIV-1 from inhibition of reverse transcription and acceleration of uncoating. J Virol. 2012;86(3):1717-27. Epub 2011/11/25. doi: JVI.05811-11 [pii]

10.1128/JVI.05811-11. PubMed PMID: 22114335; PMCID: 3264337.

73.       Diaz-Griffero F. The Role of TNPO3 in HIV-1 Replication. Mol Biol Int. 2012;2012:868597. Epub 2012/08/14. doi: 10.1155/2012/868597. PubMed PMID: 22888429; PMCID: 3409535.

74.       Di Nunzio F, Danckaert A, Fricke T, Perez P, Fernandez J, Perret E, Roux P, Shorte S, Charneau P, Diaz-Griffero F, Arhel NJ. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration. PLoS One. 2012;7(9):e46037. doi: 10.1371/journal.pone.0046037. PubMed PMID: 23049930; PMCID: 3457934.

75.       Brandariz-Nunez A, Valle-Casuso JC, White TE, Laguette N, Benkirane M, Brojatsch J, Diaz-Griffero F. Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. Retrovirology. 2012;9:49. doi: 10.1186/1742-4690-9-49. PubMed PMID: 22691373; PMCID: 3410799.

76.       Biris N, Yang Y, Taylor AB, Tomashevski A, Guo M, Hart PJ, Diaz-Griffero F, Ivanov DN. Structure of the rhesus monkey TRIM5alpha PRYSPRY domain, the HIV capsid recognition module. Proc Natl Acad Sci U S A. 2012;109(33):13278-83. Epub 2012/08/01. doi: 1203536109 [pii]

10.1073/pnas.1203536109. PubMed PMID: 22847415; PMCID: 3421187.

77.       Roa A, Hayashi F, Yang Y, Lienlaf M, Zhou J, Shi J, Watanabe S, Kigawa T, Yokoyama S, Aiken C, Diaz-Griffero F. RING Domain Mutations Uncouple TRIM5alpha Restriction of HIV-1 From Inhibition of Reverse Transcription and Acceleration of Uncoating. J Virol. 2011. Epub 2011/11/25. doi: JVI.05811-11 [pii]

10.1128/JVI.05811-11. PubMed PMID: 22114335.

78.       Lienlaf M, Hayashi F, Di Nunzio F, Tochio N, Kigawa T, Yokoyama S, Diaz-Griffero F. Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by TRIM5alpha(rh): structure of the RING domain of TRIM5alpha. J Virol. 2011;85(17):8725-37. Epub 2011/07/08. doi: JVI.00497-11 [pii]

10.1128/JVI.00497-11. PubMed PMID: 21734049; PMCID: 3165826.

79.       Diaz-Griffero F, Gallo DE, Hope TJ, Sodroski J. Trafficking of some old world primate TRIM5alpha proteins through the nucleus. Retrovirology. 2011;8(1):38. Epub 2011/05/18. doi: 1742-4690-8-38 [pii]

10.1186/1742-4690-8-38. PubMed PMID: 21575157.

80.       Diaz-Griffero F. Caging the Beast: TRIM5alpha Binding to the HIV-1 Core. Viruses. 2011;3(5):423-8. Epub 2011/10/14. doi: 10.3390/v3050423

viruses-03-00423 [pii]. PubMed PMID: 21994740; PMCID: 3186010.

81.       Sastri J, O'Connor C, Danielson CM, McRaven M, Perez P, Diaz-Griffero F, Campbell EM. Identification of residues within the L2 region of rhesus TRIM5alpha that are required for retroviral restriction and cytoplasmic body localization. Virology. 2010;405(1):259-66. Epub 2010/07/17. doi: S0042-6822(10)00397-1 [pii]

10.1016/j.virol.2010.06.015. PubMed PMID: 20633914; PMCID: 2914212.

82.       Pena-Cruz V, McDonough SM, Diaz-Griffero F, Crum CP, Carrasco RD, Freeman GJ. PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate antigen-presenting cell activity. J Invest Dermatol. 2010;130(9):2222-30. Epub 2010/05/07. doi: jid2010127 [pii]

10.1038/jid.2010.127. PubMed PMID: 20445553; PMCID: 2927196.

83.       Gosselin A, Monteiro P, Chomont N, Diaz-Griffero F, Said EA, Fonseca S, Wacleche V, El-Far M, Boulassel MR, Routy JP, Sekaly RP, Ancuta P. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J Immunol. 2010;184(3):1604-16. Epub 2010/01/01. doi: jimmunol.0903058 [pii]

10.4049/jimmunol.0903058. PubMed PMID: 20042588.

84.       Torimiro JN, Javanbakht H, Diaz-Griffero F, Kim J, Carr JK, Carrington M, Sawitzke J, Burke DS, Wolfe ND, Dean M, Sodroski J. A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies. Virology. 2009;391(1):140-7. doi: S0042-6822(09)00338-9 [pii]

10.1016/j.virol.2009.05.038. PubMed PMID: 19577266.

85.       Mani M, Carrasco DE, Zhang Y, Takada K, Gatt ME, Dutta-Simmons J, Ikeda H, Diaz-Griffero F, Pena-Cruz V, Bertagnolli M, Myeroff LL, Markowitz SD, Anderson KC, Carrasco DR. BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells. Cancer Res. 2009;69(19):7577-86. Epub 2009/09/10. doi: 0008-5472.CAN-09-0773 [pii]

10.1158/0008-5472.CAN-09-0773. PubMed PMID: 19738061.

86.       Diaz-Griffero F, Qin XR, Hayashi F, Kigawa T, Finzi A, Sarnak Z, Lienlaf M, Yokoyama S, Sodroski J. A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction. J Virol. 2009;83(20):10737-51. Epub 2009/08/07. doi: JVI.01307-09 [pii]

10.1128/JVI.01307-09. PubMed PMID: 19656869; PMCID: 2753111.

87.       Taube R, Zhu Q, Xu C, Diaz-Griffero F, Sui J, Kamau E, Dwyer M, Aird D, Marasco WA. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles. PLoS ONE. 2008;3(9):e3181. Epub 2008/09/12. doi: 10.1371/journal.pone.0003181. PubMed PMID: 18784843; PMCID: 2527531.

88.       Kar AK, Diaz-Griffero F, Li Y, Li X, Sodroski J. Biochemical and biophysical characterization of a chimeric TRIM21-TRIM5alpha protein. J Virol. 2008;82(23):11669-81. doi: JVI.01559-08 [pii]

10.1128/JVI.01559-08. PubMed PMID: 18799572.

89.       Diaz-Griffero F, Taube R, Muehlbauer SM, Brojatsch J. Efficient production of HIV-1 viral-like particles in mouse cells. Biochem Biophys Res Commun. 2008;368(3):463-9. Epub 2008/02/05. doi: S0006-291X(07)02800-8 [pii]

10.1016/j.bbrc.2007.12.195. PubMed PMID: 18241668.

90.       Diaz-Griffero F, Perron M, McGee-Estrada K, Hanna R, Maillard PV, Trono D, Sodroski J. A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus. Virology. 2008;378(2):233-42. Epub 2008/07/01. doi: S0042-6822(08)00310-3 [pii]

10.1016/j.virol.2008.05.008. PubMed PMID: 18586294; PMCID: 2597210.

91.       Li X, Gold B, O'HUigin C, Diaz-Griffero F, Song B, Si Z, Li Y, Yuan W, Stremlau M, Mische C, Javanbakht H, Scally M, Winkler C, Dean M, Sodroski J. Unique features of TRIM5alpha among closely related human TRIM family members. Virology. 2007;360(2):419-33. PubMed PMID: 17156811.

92.       Javanbakht H, Diaz-Griffero F, Yuan W, Yeung DF, Li X, Song B, Sodroski J. The ability of multimerized cyclophilin A to restrict retrovirus infection. Virology. 2007. PubMed PMID: 17574642.

93.       Diaz-Griffero F, Kar A, Perron M, Xiang SH, Javanbakht H, Li X, Sodroski J. Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5alpha B-box 2 domain. J Virol. 2007;81(19):10362-78. Epub 2007/07/13. doi: JVI.00703-07 [pii]

10.1128/JVI.00703-07. PubMed PMID: 17626085; PMCID: 2045480.

94.       Diaz-Griffero F, Kar A, Lee M, Stremlau M, Poeschla E, Sodroski J. Comparative requirements for the restriction of retrovirus infection by TRIM5alpha and TRIMCyp. Virology. 2007. PubMed PMID: 17920096.

95.       Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI, Sodroski J. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci U S A. 2006;103(14):5514-9. PubMed PMID: 16540544.

96.       Javanbakht H, Yuan W, Yeung DF, Song B, Diaz-Griffero F, Li Y, Li X, Stremlau M, Sodroski J. Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology. 2006;353(1):234-46. PubMed PMID: 16808955.

97.       Diaz-Griffero F, Vandegraaff N, Li Y, McGee-Estrada K, Stremlau M, Welikala S, Si Z, Engelman A, Sodroski J. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1. Virology. 2006;351(2):404-19. PubMed PMID: 16650449.

98.       Diaz-Griffero F, Li X, Javanbakht H, Song B, Welikala S, Stremlau M, Sodroski J. Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Virology. 2006;349(2):300-15. PubMed PMID: 16472833.

99.       Diaz-Griffero F, Espinoza Cancino C, Medina Arevalo C, Arce-Johnson P. Expression of the crucifer-infecting TMV-Cg movement protein in tobacco plants complements in trans a TMV-U1 trafficking-deficient mutant. Biol Res. 2006;39(2):269-79. PubMed PMID: 16874402.

100.     Song B, Diaz-Griffero F, Park DH, Rogers T, Stremlau M, Sodroski J. TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity. Virology. 2005. PubMed PMID: 16183097.

101.     Mische CC, Javanbakht H, Song B, Diaz-Griffero F, Stremlau M, Strack B, Si Z, Sodroski J. Retroviral restriction factor TRIM5alpha is a trimer. J Virol. 2005;79(22):14446-50. PubMed PMID: 16254380.

102.     Javanbakht H, Diaz-Griffero F, Stremlau M, Si Z, Sodroski J. The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5alpha. J Biol Chem. 2005;280(29):26933-40. PubMed PMID: 15897199.

103.     Diaz-Griffero F, Jackson AP, Brojatsch J. Cellular uptake of avian leukosis virus subgroup B is mediated by clathrin. Virology. 2005;337(1):45-54. PubMed PMID: 15914219.

104.     Diaz-Griffero F, Hoschander SA, Brojatsch J. Bystander killing during avian leukosis virus subgroup B infection requires TVB(S3) signaling. J Virol. 2003;77(23):12552-61. PubMed PMID: 14610178.

105.     Diaz-Griffero F, Hoschander SA, Brojatsch J. Endocytosis is a critical step in entry of subgroup B avian leukosis viruses. J Virol. 2002;76(24):12866-76. PubMed PMID: 12438612.

106.     Chi Y, Diaz-Griffero F, Wang C, Young JA, Brojatsch J. An NF-kappa B-dependent survival pathway protects against cell death induced by TVB receptors for avian leukosis viruses. J Virol. 2002;76(11):5581-7. PubMed PMID: 11991986.