Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA

Retrovirology

Volumn 10, Issue 1, 2013, Pages

  Michailidis, Eleftherios ^a   Ryan, Emily M ^a   Hachiya, Atsuko ^b   Kirby, Karen A ^a   Marchand, Bruno ^a   Leslie, Maxwell D ^a   Huber, Andrew D ^a   Ong, Yee T ^a   Jackson, Jacob C ^a   Singh, Kamalendra ^a   Kodama, Eiichi N ^c   Mitsuya, Hiroaki ^d,e   Parniak, Michael A ^f   Sarafianos, Stefan G ^a  

^a University of Missouri   (United States)

^b NATIONAL HOSPITAL ORGANIZATION NAGOYA MEDICAL CENTER   (Japan)

^c TOHOKU UNIVERSITY   (Japan)

^d KUMAMOTO UNIVERSITY   (Japan)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

EFdA; HIV 1; K65R; RT

Indexed keywords

4' ETHYNYL 2 FLUORO 2' DEOXYADENOSINE; DEOXYADENOSINE TRIPHOSPHATE; DNA; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; TENOFOVIR; UNCLASSIFIED DRUG;

ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONTROLLED STUDY; DNA SEQUENCE; ENZYME SUBSTRATE; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR MECHANICS; NONHUMAN; VIRUS INHIBITION; VIRUS REPLICATION; VIRUS STRAIN; WILD TYPE;

ADENINE; ANTI-HIV AGENTS; CELL LINE; DEOXYADENOSINES; DRUG RESISTANCE, VIRAL; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MICROBIAL SENSITIVITY TESTS; MUTANT PROTEINS; MUTATION, MISSENSE; ORGANOPHOSPHONATES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84879236151     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-10-65     Document Type: Article

References (72)

1. Parniak MA, Sluis-Cremer N. Inhibitors of HIV-1 reverse transcriptase. Advances in pharmacology (San Diego, Calif) 2000, 49:67-109.
2. Sharma PL, Nurpeisov V, Hernandez-Santiago B, Beltran T, Schinazi RF. Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Curr Top Med Chem 2004, 4:895-919.
3. Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, Thompson MA, Carpenter CC, Fischl MA, Gazzard BG, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. Top HIV Med 2006, 14:827-843.
4. Schinazi RF, Hernandez-Santiago BI, Hurwitz SJ. Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses. Antiviral Res 2006, 71:322-334. 10.1016/j.antiviral.2006.03.012, 16716415.
5. De Clercq E. Anti-HIV drugs. Verh K Acad Geneeskd Belg 2007, 69:81-104.
6. Sluis-Cremer N, Tachedjian G. Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors. Virus Res 2008, 134:147-156. 10.1016/j.virusres.2008.01.002, 2745993, 18372072.
7. Deval J. Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs 2009, 69:151-166. 10.2165/00003495-200969020-00002, 19228073.
8. Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, Hughes SH, Arnold E. Structure and Function of HIV-1 Reverse Transcriptase: Molecular Mechanisms of Polymerization and Inhibition. J Mol Biol 2009, 385:693-713. 10.1016/j.jmb.2008.10.071, 2881421, 19022262.
9. Ren J, Esnouf R, Garman E, Somers D, Ross C, Kirby I, Keeling J, Darby G, Jones Y, Stuart D, et al. High resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nat Struct Biol 1995, 2:293-302. 10.1038/nsb0495-293, 7540934.
10. Ding J, Das K, Hsiou Y, Sarafianos SG, Clark AD, Jacobo-Molina A, Tantillo C, Hughes SH, Arnold E. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution. J Mol Biol 1998, 284:1095-1111. 10.1006/jmbi.1998.2208, 9837729.
11. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992, 256:1783-1790. 10.1126/science.1377403, 1377403.
12. Rodgers DW, Gamblin SJ, Harris BA, Ray S, Culp JS, Hellmig B, Woolf DJ, Debouck C, Harrison SC. The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc Natl Acad Sci USA 1995, 92:1222-1226. 10.1073/pnas.92.4.1222, 42671, 7532306.
13. Hsiou Y, Ding J, Das K, Clark AD, Hughes SH, Arnold E. Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure 1996, 4:853-860. 10.1016/S0969-2126(96)00091-3, 8805568.
14. Spence RA, Kati WM, Anderson KS, Johnson KA. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 1995, 267:988-993. 10.1126/science.7532321, 7532321.
15. Rittinger K, Divita G, Goody RS. Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors. Proc Natl Acad Sci USA 1995, 92:8046-8049. 10.1073/pnas.92.17.8046, 41283, 7544013.
16. Sluis-Cremer N, Arion D, Parniak MA. Molecular mechanisms of HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTIs). Cell Mol Life Sci 2000, 57:1408-1422. 10.1007/PL00000626, 11078020.
17. Menendez-Arias L. Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Virus Res 2008, 134:124-146. 10.1016/j.virusres.2007.12.015, 18272247.
18. Martin-Hernandez AM, Domingo E, Menendez-Arias L. Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. EMBO J 1996, 15:4434-4442. 452167, 8861970.
19. Gao G, Orlova M, Georgiadis MM, Hendrickson WA, Goff SP. Conferring RNA polymerase activity to a DNA polymerase: a single residue in reverse transcriptase controls substrate selection. Proc Natl Acad Sci USA 1997, 94:407-411. 10.1073/pnas.94.2.407, 19524, 9012795.
20. Gao HQ, Boyer PL, Sarafianos SG, Arnold E, Hughes SH. The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. J Mol Biol 2000, 300:403-418. 10.1006/jmbi.2000.3823, 10873473.
21. Sarafianos SG, Das K, Clark AD, Ding J, Boyer PL, Hughes SH, Arnold E. Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc Natl Acad Sci USA 1999, 96:10027-10032. 10.1073/pnas.96.18.10027, 17836, 10468556.
22. Tisdale M, Kemp SD, Parry NR, Larder BA. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA 1993, 90:5653-5656. 10.1073/pnas.90.12.5653, 46779, 7685907.
23. Feng JY, Anderson KS. Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. Biochemistry 1999, 38:9440-9448. 10.1021/bi990709m, 10413520.
24. Back NK, Nijhuis M, Keulen W, Boucher CA, Oude Essink BO, van Kuilenburg AB, van Gennip AH, Berkhout B. Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J 1996, 15:4040-4049. 452124, 8670908.
25. Arion D, Kaushik N, McCormick S, Borkow G, Parniak MA. Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. Biochemistry 1998, 37:15908-15917. 10.1021/bi981200e, 9843396.
26. Meyer PR, Matsuura SE, So AG, Scott WA. Unblocking of chain-terminated primer by HIV-1 reverse transcriptase through a nucleotide-dependent mechanism. Proc Natl Acad Sci USA 1998, 95:13471-13476. 10.1073/pnas.95.23.13471, 24843, 9811824.
27. Meyer PR, Matsuura SE, Mian AM, So AG, Scott WA. A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol Cell 1999, 4:35-43. 10.1016/S1097-2765(00)80185-9, 10445025.
28. Meyer PR, Matsuura SE, Tolun AA, Pfeifer I, So AG, Mellors JW, Scott WA. Effects of specific zidovudine resistance mutations and substrate structure on nucleotide-dependent primer unblocking by human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 2002, 46:1540-1545. 10.1128/AAC.46.5.1540-1545.2002, 127181, 11959594.
29. Boyer PL, Sarafianos SG, Arnold E, Hughes SH. Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase. J Virol 2001, 75:4832-4842. 10.1128/JVI.75.10.4832-4842.2001, 114238, 11312355.
30. Larder BA, Kemp SD. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 1989, 246:1155-1158. 10.1126/science.2479983, 2479983.
31. Winters MA, Shafer RW, Jellinger RA, Mamtora G, Gingeras T, Merigan TC. Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob Agents Chemother 1997, 41:757-762. 163789, 9087484.
32. Harrigan PR, Stone C, Griffin P, Najera I, Bloor S, Kemp S, Tisdale M, Larder B. Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. J Infect Dis 2000, 181:912-920. 10.1086/315317, 10720512.
33. Margot NA, Lu B, Cheng A, Miller MD, Study T. Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903. HIV Med 2006, 7:442-450. 10.1111/j.1468-1293.2006.00404.x, 16925730.
34. Wainberg MA, Miller MD, Quan Y, Salomon H, Mulato AS, Lamy PD, Margot NA, Anton KE, Cherrington JM. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther 1999, 4:87-94.
35. Margot NA, Isaacson E, McGowan I, Cheng AK, Schooley RT, Miller MD. Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. AIDS 2002, 16:1227-1235. 10.1097/00002030-200206140-00004, 12045487.
36. Feng JY, Myrick FT, Margot NA, Mulamba GB, Rimsky L, Borroto-Esoda K, Selmi B, Canard B. Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Nucleosides Nucleotides Nucleic Acids 2006, 25:89-107. 10.1080/15257770500379157, 16440988.
37. Shah FS, Curr KA, Hamburgh ME, Parniak M, Mitsuya H, Arnez JG, Prasad VR. Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. J Biol Chem 2000, 275:27037-27044.
38. Frankel FA, Invernizzi CF, Oliveira M, Wainberg MA. Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. AIDS 2007, 21:665-675. 10.1097/QAD.0b013e3280187505, 17413687.
39. Parikh UM, Zelina S, Sluis-Cremer N, Mellors JW. Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. AIDS 2007, 21:1405-1414. 10.1097/QAD.0b013e3281ac229b, 17589186.
40. White KL, Margot NA, Ly JK, Chen JM, Ray AS, Pavelko M, Wang R, McDermott M, Swaminathan S, Miller MD. A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. AIDS 2005, 19:1751-1760. 10.1097/01.aids.0000189851.21441.f1, 16227782.
41. Deval J, Navarro JM, Selmi B, Courcambeck J, Boretto J, Halfon P, Garrido-Urbani S, Sire J, Canard B. A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. J Biol Chem 2004, 279:25489-25496. 10.1074/jbc.M313534200, 15044478.
42. Deval J, White KL, Miller MD, Parkin NT, Courcambeck J, Halfon P, Selmi B, Boretto J, Canard B. Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. J Biol Chem 2004, 279:509-516.
43. White KL, Chen JM, Feng JY, Margot NA, Ly JK, Ray AS, Macarthur HL, McDermott MJ, Swaminathan S, Miller MD. The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. Antivir Ther 2006, 11:155-163.
44. Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, Tu X, Clark AD, Boyer PL, Hou X, et al. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J Biol Chem 2009, 284:35092-35100. 10.1074/jbc.M109.022525, 2787370, 19812032.
45. Kawamoto A, Kodama E, Sarafianos SG, Sakagami Y, Kohgo S, Kitano K, Ashida N, Iwai Y, Hayakawa H, Nakata H, et al. 2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. Int J Biochem Cell Biol 2008, 40:2410-2420. 10.1016/j.biocel.2008.04.007, 18487070.
46. Michailidis E, Marchand B, Kodama EN, Singh K, Matsuoka M, Kirby KA, Ryan EM, Sawani AM, Nagy E, Ashida N, et al. Mechanism of inhibition of HIV-1 reverse transcriptase by 4'-Ethynyl-2-fluoro-2'-deoxyadenosine triphosphate, a translocation-defective reverse transcriptase inhibitor. J Biol Chem 2009, 284:35681-35691. 10.1074/jbc.M109.036616, 2790999, 19837673.
47. Marchand B, Gotte M. Site-specific footprinting reveals differences in the translocation status of HIV-1 reverse transcriptase. Implications for polymerase translocation and drug resistance. J Biol Chem 2003, 278:35362-35372. 10.1074/jbc.M304262200, 12819205.
48. Ray AS, Murakami E, Basavapathruni A, Vaccaro JA, Ulrich D, Chu CK, Schinazi RF, Anderson KS. Probing the molecular mechanisms of AZT drug resistance mediated by HIV-1 reverse transcriptase using a transient kinetic analysis. Biochemistry 2003, 42:8831-8841. 10.1021/bi034435l, 12873144.
49. Tu X, Das K, Han Q, Bauman JD, Clark AD, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, et al. Structural basis of HIV-1 resistance to AZT by excision. Nat Struct Mol Biol 2010, 17:1202-1209. 10.1038/nsmb.1908, 2987654, 20852643.
50. Winters B, Montaner J, Harrigan PR, Gazzard B, Pozniak A, Miller MD, Emery S, van Leth F, Robinson P, Baxter JD, et al. Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data. J Acquir Immune Defic Syndr 2008, 48:26-34. 10.1097/QAI.0b013e31816d9bf4, 18360290.
51. Murphey-Corb M, Rajakumar P, Michael H, Nyaundi J, Didier PJ, Reeve AB, Mitsuya H, Sarafianos SG, Parniak MA. Response of simian immunodeficiency virus to the novel nucleoside reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine in vitro and in vivo. Antimicrob Agents Chemother 2012, 56:4707-4712. 10.1128/AAC.00723-12, 3421895, 22713337.
52. St Clair MH, Martin JL, Tudor-Williams G, Bach MC, Vavro CL, King DM, Kellam P, Kemp SD, Larder BA. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 1991, 253:1557-1559. 10.1126/science.1716788, 1716788.
53. Quan Y, Gu Z, Li X, Liang C, Parniak MA, Wainberg MA. Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. J Mol Biol 1998, 277:237-247. 10.1006/jmbi.1997.1592, 9514745.
54. Bazmi HZ, Hammond JL, Cavalcanti SC, Chu CK, Schinazi RF, Mellors JW. In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. Antimicrob Agents Chemother 2000, 44:1783-1788. 10.1128/AAC.44.7.1783-1788.2000, 89962, 10858331.
55. Parikh UM, Bacheler L, Koontz D, Mellors JW. The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. J Virol 2006, 80:4971-4977. 10.1128/JVI.80.10.4971-4977.2006, 1472090, 16641288.
56. Kodama EI, Kohgo S, Kitano K, Machida H, Gatanaga H, Shigeta S, Matsuoka M, Ohrui H, Mitsuya H. 4'-Ethynyl nucleoside analogs: potent inhibitors of multidrug-resistant human immunodeficiency virus variants in vitro. Antimicrob Agents Chemother 2001, 45:1539-1546. 10.1128/AAC.45.5.1539-1546.2001, 90502, 11302824.
57. Larder BA. 3'-Azido-3'-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother 1992, 36:2664-2669. 10.1128/AAC.36.12.2664, 245525, 1282792.
58. Selmi B, Deval J, Alvarez K, Boretto J, Sarfati S, Guerreiro C, Canard B. The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. J Biol Chem 2003, 278:40464-40472. 10.1074/jbc.M302928200, 12902345.
59. Boucher CA, Cammack N, Schipper P, Schuurman R, Rouse P, Wainberg MA, Cameron JM. High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1993, 37:2231-2234. 10.1128/AAC.37.10.2231, 192256, 7504909.
60. Boyer PL, Sarafianos SG, Arnold E, Hughes SH. The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. J Virol 2002, 76:3248-3256. 10.1128/JVI.76.7.3248-3256.2002, 136050, 11884549.
61. Gotte M, Arion D, Parniak MA, Wainberg MA. The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. J Virol 2000, 74:3579-3585. 10.1128/JVI.74.8.3579-3585.2000, 111867, 10729133.
62. Hachiya A, Marchand B, Kirby KA, Michailidis E, Tu X, Palczewski K, Ong YT, Li Z, Griffin DT, Schuckmann MM, et al. HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors. J Biol Chem 2012, 287:29988-29999. 10.1074/jbc.M112.351551, 22761416.
63. Hachiya A, Gatanaga H, Kodama E, Ikeuchi M, Matsuoka M, Harada S, Mitsuya H, Kimura S, Oka S. Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients. Virology 2004, 327:215-224. 10.1016/j.virol.2004.07.001, 15351209.
64. Hachiya A, Kodama EN, Sarafianos SG, Schuckmann MM, Sakagami Y, Matsuoka M, Takiguchi M, Gatanaga H, Oka S. Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J Virol 2008, 82:3261-3270. 10.1128/JVI.01154-07, 2268505, 18216099.
65. Bauman JD, Das K, Ho WC, Baweja M, Himmel DM, Clark AD, Oren DA, Boyer PL, Hughes SH, Shatkin AJ, Arnold E. Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design. Nucleic Acids Res 2008, 36:5083-5092. 10.1093/nar/gkn464, 2528191, 18676450.
66. Schuckmann MM, Marchand B, Hachiya A, Kodama EN, Kirby KA, Singh K, Sarafianos SG. The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. J Biol Chem 2010, 285:38700-38709. 10.1074/jbc.M110.153783, 2992303, 20876531.
67. Ndongwe TP, Adedeji AO, Michailidis E, Ong YT, Hachiya A, Marchand B, Ryan EM, Rai DK, Kirby KA, Whatley AS, et al. Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Nucleic Acids Res 2012, 40:345-359. 10.1093/nar/gkr694, 3245923, 21908397.
68. Kirby KA, Marchand B, Ong YT, Ndongwe TP, Hachiya A, Michailidis E, Leslie MD, Sietsema DV, Fetterly TL, Dorst CA, et al. Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase. Antimicrob Agents Chemother 2012, 56(4):2048-61. 10.1128/AAC.06000-11, 3318313, 22252812.
69. Sarafianos SG, Clark AD, Tuske S, Squire CJ, Das K, Sheng D, Ilankumaran P, Ramesha AR, Kroth H, Sayer JM, et al. Trapping HIV-1 reverse transcriptase before and after translocation on DNA. J Biol Chem 2003, 278:16280-16288. 10.1074/jbc.M212911200, 12554739.
70. Ohrui H, Kohgo S, Hayakawa H, Kodama E, Matsuoka M, Nakata T, Mitsuya H. 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine: a nucleoside reverse transcriptase inhibitor with highly potent activity against wide spectrum of HIV-1 strains, favorable toxic profiles, and stability in plasma. Nucleosides Nucleotides Nucleic Acids 2007, 26(10-12):1543-6. 10.1080/15257770701545218, 18066823.
71. Biaglow JE, Kachur AV. The generation of hydroxyl radicals in the reaction of molecular oxygen with polyphosphate complexes of ferrous ion. Radiat Res 1997, 148:181-187. 10.2307/3579576, 9254738.
72. Tuske S, Sarafianos SG, Clark AD, Ding J, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, et al. Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat Struct Mol Biol 2004, 11:469-474. 10.1038/nsmb760, 15107837.