Nonhuman Primates and Humanized Mice for Studies of HIV-1 Integrase Inhibitors: A Review

Said A. Hassounah, Thibault Mesplède, Mark A. Wainberg

Abstract


Since the discovery of the first inhibitors of HIV replication, drug resistance has been a major problem in HIV therapy, due, in part, to the high mutation rate of HIV. Therefore, the development of a predictive animal model is important to identify impending resistance mutations and to possibly inform treatment decisions. Significant advances have been made possible through use of nonhuman primates infected by SIV, SHIV, and stHIV-1, and use of humanized mouse models of HIV-1 infections. In this review, we describe some of the findings from animal models used for the preclinical testing of integrase strand transfer inhibitors as well as other antiretroviral drugs. These models have led to important findings about the potential role of integrase strand transfer inhibitors in both the prevention and treatment of HIV-1 infection.


Keywords


nonhuman primates; integrase strand transfer inhibitors; integrase; drug resistance mutations; simian immunodeficiency virus (SIV); simian-human immunodeficiency virus (SHIV); simian-tropic human immunodeficiency virus (stHIV-1)

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References


Kraus G, Werner A, Baier M, Binniger D, Ferdinand FJ, Norley S, Kurth R. Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys. Proc Natl Acad Sci USA. 1989;86(8):2892-6. PubMed PMID: 2468160. Pubmed Central PMCID: 287025. Epub 1989/04/01.

Ohta Y, Masuda T, Tsujimoto H, Ishikawa K, Kodama T, Morikawa S, Nakai M, Honjo S, Hayami M. Isolation of simian immunodeficiency virus from African green monkeys and seroepidemiologic survey of the virus in various non-human primates. Int J Cancer. 1988;41(1):115-22. PubMed PMID: 2447023. Epub 1988/01/15.

Daniel MD, Letvin NL, King NW, Kannagi M, Sehgal PK, Hunt RD, Kanki PJ, Essex M, Desrosiers RC. Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science. 1985;228(4704):1201-4. PubMed PMID: 3159089. Epub 1985/06/07.

Letvin NL, Daniel MD, Sehgal PK, Desrosiers RC, Hunt RD, Waldron LM, MacKey JJ, Schmidt DK, Chalifoux LV, King NW. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science. 1985;230(4721):71-3. PubMed PMID: 2412295. Epub 1985/10/04.

Kestler H, Kodama T, Ringler D, Marthas M, Pedersen N, Lackner A, Regier D, Sehgal P, Daniel M, King N, et al. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990;248(4959):1109-12. PubMed PMID: 2160735. Epub 1990/06/01.

Letvin NL, Eaton KA, Aldrich WR, Sehgal PK, Blake BJ, Schlossman SF, King NW, Hunt RD. Acquired immunodeficiency syndrome in a colony of macaque monkeys. Proc Natl Acad Sci USA. 1983;80(9):2718-22. PubMed PMID: 6221343. Pubmed Central PMCID: 393899. Epub 1983/05/01.

King NW, Hunt RD, Letvin NL. Histopathologic changes in macaques with an acquired immunodeficiency syndrome (AIDS). Am J Pathol. 1983;113(3):382-8. PubMed PMID: 6316791. Pubmed Central PMCID: 1916356. Epub 1983/12/01.

Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature. 1989;339(6223):389-92. PubMed PMID: 2786147. Epub 1989/06/01. doi: 10.1038/339389a0

Naidu YM, Kestler HW, 3rd, Li Y, Butler CV, Silva DP, Schmidt DK, Troup CD, Sehgal PK, Sonigo P, Daniel MD, et al. Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol. 1988;62(12):4691-6. PubMed PMID: 2846880. Pubmed Central PMCID: 253583. Epub 1988/12/01.

Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM, Hahn BH. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature. 1999;397(6718):436-41. PubMed PMID: 9989410. Epub 1999/02/16. doi: 10.1038/17130

Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: scientific and public health implications. Science. 2000;287(5453):607-14. PubMed PMID: 10649986. Epub 2000/01/29.

Chen Z, Luckay A, Sodora DL, Telfer P, Reed P, Gettie A, Kanu JM, Sadek RF, Yee J, Ho DD, Zhang L, Marx PA. Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus-infected sooty mangabeys. J Virol. 1997;71(5):3953-60. PubMed PMID: 9094672. Pubmed Central PMCID: 191547. Epub 1997/05/01.

Keele BF, Jones JH, Terio KA, Estes JD, Rudicell RS, Wilson ML, Li Y, Learn GH, Beasley TM, Schumacher-Stankey J, Wroblewski E, Mosser A, Raphael J, Kamenya S, Lonsdorf EV, Travis DA, Mlengeya T, Kinsel MJ, Else JG, Silvestri G, Goodall J, Sharp PM, Shaw GM, Pusey AE, Hahn BH. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature. 2009;460(7254):515-9. PubMed PMID: 19626114. Pubmed Central PMCID: 2872475. Epub 2009/07/25. doi: 10.1038/nature08200

Hirsch VM, Lifson JD. Simian immunodeficiency virus infection of monkeys as a model system for the study of AIDS pathogenesis, treatment, and prevention. Adv Pharmacol. 2000;49:437-77. PubMed PMID: 11013771. Epub 2000/10/03.

Stone M, Keele BF, Ma ZM, Bailes E, Dutra J, Hahn BH, Shaw GM, Miller CJ. A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol. 2010;84(14):7083-95. PubMed PMID: 20463069. Pubmed Central PMCID: 2898254. Epub 2010/05/14. doi: 10.1128/JVI.00481-10

Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, Grayson T, Sun C, Chen Y, Yeh WW, Letvin NL, Mascola JR, Nabel GJ, Haynes BF, Bhattacharya T, Perelson AS, Korber BT, Hahn BH, Shaw GM. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med. 2009;206(5):1117-34. PubMed PMID: 19414559. Pubmed Central PMCID: 2715022. Epub 2009/05/06. doi: 10.1084/jem.20082831

Ma ZM, Keele BF, Qureshi H, Stone M, Desilva V, Fritts L, Lifson JD, Miller CJ. SIVmac251 is inefficiently transmitted to rhesus macaques by penile inoculation with a single SIVenv variant found in ramp-up phase plasma. AIDS Res Hum Retroviruses. 2011;27(12):1259-69. PubMed PMID: 21732792. Pubmed Central PMCID: 3227244. Epub 2011/07/08. doi: 10.1089/aid.2011.0090

Abel K, Pahar B, Van Rompay KK, Fritts L, Sin C, Schmidt K, Colon R, McChesney M, Marthas ML. Rapid virus dissemination in infant macaques after oral simian immunodeficiency virus exposure in the presence of local innate immune responses. J Virol. 2006;80(13):6357-67. PubMed PMID: 16775324. Pubmed Central PMCID: 1488945. Epub 2006/06/16. doi: 10.1128/JVI.02240-05

Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, Espeseth A, Gabryelski L, Schleif W, Blau C, Miller MD. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science. 2000;287(5453):646-50. PubMed PMID: 10649997. Epub 2000/01/29.

Engelman A, Cherepanov P. The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol. 2012;10(4):279-90. PubMed PMID: 22421880. Pubmed Central PMCID: 3588166. Epub 2012/03/17. doi: 10.1038/nrmicro2747

Delelis O, Carayon K, Saib A, Deprez E, Mouscadet JF. Integrase and integration: biochemical activities of HIV-1 integrase. Retrovirology. 2008;5:114. PubMed PMID: 19091057. Pubmed Central PMCID: 2615046. Epub 2008/12/19. doi: 10.1186/1742-4690-5-114

Craigie R, Bushman FD. HIV DNA integration. Cold Spring Harb Perspect Med. 2012;2(7):a006890. PubMed PMID: 22762018. Pubmed Central PMCID: 3385939. Epub 2012/07/05. doi: 10.1101/cshperspect.a006890

Grobler JA, Stillmock K, Hu B, Witmer M, Felock P, Espeseth AS, Wolfe A, Egbertson M, Bourgeois M, Melamed J, Wai JS, Young S, Vacca J, Hazuda DJ. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc Natl Acad Sci USA. 2002;99(10):6661-6. PubMed PMID: 11997448. Pubmed Central PMCID: 124459. Epub 2002/05/09. doi: 10.1073/pnas.092056199

Hassounah SA, Mesplede T, Quashie PK, Oliveira M, Sandstrom PA, Wainberg MA. The effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. J Virol. 2014. PubMed PMID: 24920794. Epub 2014/06/13. doi: 10.1128/JVI.00947-14

Lewis MG, Norelli S, Collins M, Barreca ML, Iraci N, Chirullo B, Yalley-Ogunro J, Greenhouse J, Titti F, Garaci E, Savarino A. Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy. Retrovirology. 2010;7:21. PubMed PMID: 20233398. Pubmed Central PMCID: 2853490. Epub 2010/03/18. doi: 10.1186/1742-4690-7-21

Hassounah SA, Mesplede T, Quashie PK, Oliveira M, Sandstrom PA, Wainberg MA. Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. J Virol. 2014;88(17):9683-92. PubMed PMID: 24920794. Pubmed Central PMCID: 4136349. Epub 2014/06/13. doi: 10.1128/JVI.00947-14

Castagna A, Maggiolo F, Penco G, Wright D, Mills A, Grossberg R, Molina JM, Chas J, Durant J, Moreno S, Doroana M, Ait-Khaled M, Huang J, Min S, Song I, Vavro C, Nichols G, Yeo JM. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J Infect Dis. 2014;210(3):354-62. PubMed PMID: 24446523. Pubmed Central PMCID: 4091579. Epub 2014/01/22. doi: 10.1093/infdis/jiu051

Mamede JI, Sitbon M, Battini JL, Courgnaud V. Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors. Retrovirology. 2013;10:77. PubMed PMID: 23883001. Pubmed Central PMCID: 3751554. Epub 2013/07/26. doi: 10.1186/1742-4690-10-77

Puras Lutzke RA, Eppens NA, Weber PA, Houghten RA, Plasterk RH. Identification of a hexapeptide inhibitor of the human immunodeficiency virus integrase protein by using a combinatorial chemical library. Proc Natl Acad Sci U S A. 1995;92(25):11456-60. PubMed PMID: 8524782. Pubmed Central PMCID: 40420. Epub 1995/12/05.

Mazumder A, Neamati N, Ojwang JO, Sunder S, Rando RF, Pommier Y. Inhibition of the human immunodeficiency virus type 1 integrase by guanosine quartet structures. Biochemistry. 1996;35(43):13762-71. PubMed PMID: 8901518. Epub 1996/10/29. doi: 10.1021/bi960541u

Savarino A, Pistello M, D’Ostilio D, Zabogli E, Taglia F, Mancini F, Ferro S, Matteucci D, De Luca L, Barreca ML, Ciervo A, Chimirri A, Ciccozzi M, Bendinelli M. Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS. Retrovirology. 2007;4:79. PubMed PMID: 17971219. Pubmed Central PMCID: 2244644. Epub 2007/11/01. doi: 10.1186/1742-4690-4-79

Egberink H, Borst M, Niphuis H, Balzarini J, Neu H, Schellekens H, De Clercq E, Horzinek M, Koolen M. Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine. Proc Natl Acad Sci USA. 1990;87(8):3087-91. PubMed PMID: 2158102. Pubmed Central PMCID: 53839. Epub 1990/04/01.

Matteucci D, Mazzetti P, Baldinotti F, Zaccaro L, Bendinelli M. The feline lymphoid cell line MBM and its use for feline immunodeficiency virus isolation and quantitation. Vet Immunol Immunopathol. 1995;46(1-2):71-82. PubMed PMID: 7618261. Epub 1995/05/01.

Atchison RE, Gosling J, Monteclaro FS, Franci C, Digilio L, Charo IF, Goldsmith MA. Multiple extracellular elements of CCR5 and HIV-1 entry: dissociation from response to chemokines. Science. 1996;274(5294):1924-6. PubMed PMID: 8943208. Epub 1996/12/13.

Kwak YT, Ivanov D, Guo J, Nee E, Gaynor RB. Role of the human and murine cyclin T proteins in regulating HIV-1 tat-activation. J Mol Biol. 1999;288(1):57-69. PubMed PMID: 10329126. Epub 1999/05/18. doi: 10.1006/jmbi.1999.2664
Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature. 1983;301(5900):527-30. PubMed PMID: 6823332. Epub 1983/02/10.

Schuler W, Weiler IJ, Schuler A, Phillips RA, Rosenberg N, Mak TW, Kearney JF, Perry RP, Bosma MJ. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986;46(7):963-72. PubMed PMID: 3093081. Epub 1986/09/26.

Berges BK, Akkina SR, Folkvord JM, Connick E, Akkina R. Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag2-/- gammac -/- (RAG-hu) mice. Virology. 2008;373(2):342-51. PubMed PMID: 18207484. Pubmed Central PMCID: 3092740. Epub 2008/01/22. doi: 10.1016/j.virol.2007.11.020

Zhang L, Kovalev GI, Su L. HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood. 2007;109(7):2978-81. PubMed PMID: 17132723. Pubmed Central PMCID: 1852218. Epub 2006/11/30. doi: 10.1182/blood-2006-07-033159

Knight A. The beginning of the end for chimpanzee experiments? Philos Ethics Humanit Med. 2008;3:16. PubMed PMID: 18518999. Pubmed Central PMCID: 2432070. Epub 2008/06/04. doi: 10.1186/1747-5341-3-16

Bettauer RH. Chimpanzees in hepatitis C virus research: 1998-2007. J Med Primatol. 2010;39(1):9-23. PubMed PMID: 19900169. Epub 2009/11/11. doi: 10.1111/j.1600-0684.2009.00390.x

Hatziioannou T, Evans DT. Animal models for HIV/AIDS research. Nat Rev Microbiol. 2012;10(12):852-67. PubMed PMID: 23154262. Epub 2012/11/17. doi: 10.1038/nrmicro2911

Blakley GB, Beamer TW, Dukelow WR. Characteristics of the menstrual cycle in nonhuman primates. IV. Timed mating in Macaca nemestrina. Lab Anim. 1981;15(4):351-3. PubMed PMID: 7341846. Epub 1981/10/01.

Wira CR, Fahey JV. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS. 2008;22(15):1909-17. PubMed PMID: 18784454. Pubmed Central PMCID: 2647143. Epub 2008/09/12. doi: 10.1097/QAD.0b013e3283060ea4

Vishwanathan SA, Guenthner PC, Lin CY, Dobard C, Sharma S, Adams DR, Otten RA, Heneine W, Hendry RM, McNicholl JM, Kersh EN. High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques. J Acquir Immune Defic Syndr. 2011;57(4):261-4. PubMed PMID: 21546848. Epub 2011/05/07. doi: 10.1097/QAI.0b013e318220ebd3

Sodora DL, Gettie A, Miller CJ, Marx PA. Vaginal transmission of SIV: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks. AIDS Res Hum Retroviruses. 1998;14 Suppl 1:S119-23. PubMed PMID: 9581895. Epub 1998/05/15.

Zhou Y, Bao R, Haigwood NL, Persidsky Y, Ho WZ. SIV infection of rhesus macaques of Chinese origin: a suitable model for HIV infection in humans. Retrovirology. 2013;10:89. PubMed PMID: 23947613. Pubmed Central PMCID: 3765527. Epub 2013/08/21. doi: 10.1186/1742-4690-10-89

Otten RA, Adams DR, Kim CN, Jackson E, Pullium JK, Lee K, Grohskopf LA, Monsour M, Butera S, Folks TM. Multiple vaginal exposures to low doses of R5 simian-human immunodeficiency virus: strategy to study HIV preclinical interventions in nonhuman primates. J Infect Dis. 2005;191(2):164-73. PubMed PMID: 15609225. Epub 2004/12/21. doi: 10.1086/426452

Livingston L, Sweeney E, Mitchell J, Luo W, Paul K, Powell N, Michael Hendry R, McNicholl J, Kersh E. Hormonal synchronization of the menstrual cycles of pigtail macaques to facilitate biomedical research including modeling HIV susceptibility. J Med Primatol. 2011;40(3):164-70. PubMed PMID: 21241313. Epub 2011/01/19. doi: 10.1111/j.1600-0684.2010.00465.x

Pilcher CD, Tien HC, Eron JJ, Jr., Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189(10):1785-92. PubMed PMID: 15122514. Epub 2004/05/04. doi: 10.1086/386333

Dobard C, Sharma S, Martin A, Pau CP, Holder A, Kuklenyik Z, Lipscomb J, Hanson DL, Smith J, Novembre FJ, Garcia-Lerma JG, Heneine W. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue. J Virol. 2012;86(2):718-25. PubMed PMID: 22072766. Pubmed Central PMCID: 3255839. Epub 2011/11/11. doi: 10.1128/JVI.05842-11

Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, Parenteau L, Cabral C, Shields J, Blackmore S, Smith JY, Brinkman AL, Peter LE, Mathew SI, Smith KM, Borducchi EN, Rosenbloom DI, Lewis MG, Hattersley J, Li B, Hesselgesser J, Geleziunas R, Robb ML, Kim JH, Michael NL, Barouch DH. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014;512(7512):74-7. PubMed PMID: 25042999. Pubmed Central PMCID: 4126858. Epub 2014/07/22. doi: 10.1038/nature13594

Li J, Lord CI, Haseltine W, Letvin NL, Sodroski J. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. J Acquir Immune Defic Syndr. 1992;5(7):639-46. PubMed PMID: 1613662. Epub 1992/01/01.

Hatziioannou T, Princiotta M, Piatak M, Jr., Yuan F, Zhang F, Lifson JD, Bieniasz PD. Generation of simian-tropic HIV-1 by restriction factor evasion. Science. 2006;314(5796):95. PubMed PMID: 17023652. Epub 2006/10/07. doi: 10.1126/science.1130994

Riddick NE, Hermann EA, Loftin LM, Elliott ST, Wey WC, Cervasi B, Taaffe J, Engram JC, Li B, Else JG, Li Y, Hahn BH, Derdeyn CA, Sodora DL, Apetrei C, Paiardini M, Silvestri G, Collman RG. A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo. PLoS Pathog. 2010;6(8):e1001064. PubMed PMID: 20865163. Pubmed Central PMCID: 2928783. Epub 2010/09/25. doi: 10.1371/journal.ppat.1001064

Evans DT, Silvestri G. Nonhuman primate models in AIDS research. Curr Opin HIV AIDS. 2013;8(4):255-61. PubMed PMID: 23615116. Pubmed Central PMCID: 3987953. Epub 2013/04/26. doi: 10.1097/COH.0b013e328361cee8

Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther. 2004;9(1):57-65. PubMed PMID: 15040537. Epub 2004/03/26.

Chen Z, Yan Y, Munshi S, Li Y, Zugay-Murphy J, Xu B, Witmer M, Felock P, Wolfe A, Sardana V, Emini EA, Hazuda D, Kuo LC. X-ray structure of simian immunodeficiency virus integrase containing the core and C-terminal domain (residues 50-293)--an initial glance of the viral DNA binding platform. J Mol Biol. 2000;296(2):521-33. PubMed PMID: 10669606. Epub 2000/02/12. doi: 10.1006/jmbi.1999.3451

Li Y, Yan Y, Zugay-Murphy J, Xu B, Cole JL, Witmer M, Felock P, Wolfe A, Hazuda D, Sardana MK, Chen Z, Kuo LC, Sardana VV. Purification, solution properties and crystallization of SIV integrase containing a continuous core and C-terminal domain. Acta Crystallogr D Biol Crystallogr. 1999;55(Pt 11):1906-10. PubMed PMID: 10531491. Epub 1999/10/26.

Reimann KA, Li JT, Veazey R, Halloran M, Park IW, Karlsson GB, Sodroski J, Letvin NL. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J Virol. 1996;70(10):6922-8. PubMed PMID: 8794335. Pubmed Central PMCID: 190741. Epub 1996/10/01.

Feinberg MB, Moore JP. AIDS vaccine models: challenging challenge viruses. Nat Med. 2002;8(3):207-10. PubMed PMID: 11875482. Epub 2002/03/05. doi: 10.1038/nm0302-207

Harouse JM, Gettie A, Tan RC, Blanchard J, Cheng-Mayer C. Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs. Science. 1999;284(5415):816-9. PubMed PMID: 10221916. Epub 1999/04/30.

Van Rompay KK. Evaluation of antiretrovirals in animal models of HIV infection. Antiviral Res. 2010;85(1):159-75. PubMed PMID: 19622373. Epub 2009/07/23. doi: 10.1016/j.antiviral.2009.07.008

Kamada K, Igarashi T, Martin MA, Khamsri B, Hatcho K, Yamashita T, Fujita M, Uchiyama T, Adachi A. Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells. Proc Natl Acad Sci USA. 2006;103(45):16959-64. PubMed PMID: 17065315. Pubmed Central PMCID: 1622925. Epub 2006/10/27. doi: 10.1073/pnas.0608289103

Na L, Tang YD, Liu JD, Yu CQ, Sun LK, Lin YZ, Wang XF, Wang X, Zhou JH. TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5alpha activity. Biochem Biophys Res Commun. 2014;446(2):470-4. PubMed PMID: 24613845. Epub 2014/03/13. doi: 10.1016/j.bbrc.2014.02.132

Wares M, Hassounah S, Mesplede T, Sandstrom PA, Wainberg MA. Simian-tropic HIV as a model to study drug resistance against integrase inhibitors. Antimicrob Agents Chemother. 2015;59(4):1942-9. PubMed PMID: 25583721. Pubmed Central PMCID: 4356797. Epub 2015/01/15. doi: 10.1128/AAC.04829-14

Shimura K, Kodama E, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, Watanabe Y, Ohata Y, Doi S, Sato M, Kano M, Ikeda S, Matsuoka M. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol. 2008;82(2):764-74. PubMed PMID: 17977962. Pubmed Central PMCID: 2224569. Epub 2007/11/06. doi: 10.1128/JVI.01534-07

Hassounah SA, Liu Y, Quashie PK, Oliveira M, Moisi D, Brenner BG, Sandstrom PA, Mesplede T, Wainberg MA. Characterization of the drug resistance profiles of integrase strand transfer inhibitors in simian immunodeficiency virus SIVmac239. J Virol. 2015;89(23):12002-13. PubMed PMID: 26378179. Pubmed Central PMCID: 4645305. Epub 2015/09/18. doi: 10.1128/JVI.02131-15

Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-8. PubMed PMID: 23830355. Epub 2013/07/09. doi: 10.1016/S0140-6736(13)61221-0

Margot NA, Hluhanich RM, Jones GS, Andreatta KN, Tsiang M, McColl DJ, White KL, Miller MD. In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4. Antiviral Res. 2012;93(2):288-96. PubMed PMID: 22197635. Epub 2011/12/27. doi: 10.1016/j.antiviral.2011.12.008

Blanco JL, Varghese V, Rhee SY, Gatell JM, Shafer RW. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis. 2011;203(9):1204-14. PubMed PMID: 21459813. Pubmed Central PMCID: 3069732. Epub 2011/04/05. doi: 10.1093/infdis/jir025

Hatano H, Lampiris H, Fransen S, Gupta S, Huang W, Hoh R, Martin JN, Lalezari J, Bangsberg D, Petropoulos C, Deeks SG. Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. J Acquir Immune Defic Syndr. 2010;54(4):389-93. PubMed PMID: 20300008. Pubmed Central PMCID: 2890029. Epub 2010/03/20. doi: 10.1097/QAI.0b013e3181c42ea4

Van Wesenbeeck L, Rondelez E, Feyaerts M, Verheyen A, Van der Borght K, Smits V, Cleybergh C, De Wolf H, Van Baelen K, Stuyver LJ. Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates. Antimicrob Agents Chemother. 2011;55(1):321-5. PubMed PMID: 20956600. Pubmed Central PMCID: 3019647. Epub 2010/10/20. doi: 10.1128/AAC.01733-09

Winters MA, Lloyd RM, Jr., Shafer RW, Kozal MJ, Miller MD, Holodniy M. Development of elvitegravir resistance and linkage of integrase inhibitor mutations with protease and reverse transcriptase resistance mutations. PLoS One. 2012;7(7):e40514. PubMed PMID: 22815755. Pubmed Central PMCID: 3399858. Epub 2012/07/21. doi: 10.1371/journal.pone.0040514

DeJesus E, Rockstroh JK, Lennox JL, Saag MS, Lazzarin A, Zhao J, Wan H, Rodgers AJ, Walker ML, Miller M, DiNubile MJ, Nguyen BY, Teppler H, Leavitt R, Sklar P. Efficacy of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: week-192 overall and subgroup analyses from STARTMRK. HIV Clin Trials. 2012;13(4):228-32. PubMed PMID: 22849964. Epub 2012/08/02. doi: 10.1310/hct1304-228

Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835):2439-48. PubMed PMID: 22748591. Epub 2012/07/04. doi: 10.1016/S0140-6736(12)60917-9

Molina JM, Lamarca A, Andrade-Villanueva J, Clotet B, Clumeck N, Liu YP, Zhong L, Margot N, Cheng AK, Chuck SL. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012;12(1):27-35. PubMed PMID: 22015077. Epub 2011/10/22. doi: 10.1016/S1473-3099(11)70249-3

Quashie PK, Mesplede T, Han YS, Oliveira M, Singhroy DN, Fujiwara T, Underwood MR, Wainberg MA. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol. 2012;86(5):2696-705. PubMed PMID: 22205735. Pubmed Central PMCID: 3302270. Epub 2011/12/30. doi: 10.1128/JVI.06591-11

Quashie PK, Mesplede T, Han YS, Veres T, Osman N, Hassounah S, Sloan RD, Xu HT, Wainberg MA. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother. 2013;57(12):6223-35. PubMed PMID: 24080645. Pubmed Central PMCID: 3837891. Epub 2013/10/02. doi: 10.1128/AAC.01835-13

Quashie PK, Oliviera M, Veres T, Osman N, Han YS, Hassounah S, Lie Y, Huang W, Mesplede T, Wainberg MA. Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. J Virol. 2015;89(6):3163-75. PubMed PMID: 25552724. Pubmed Central PMCID: 4337543. Epub 2015/01/02. doi: 10.1128/JVI.03353-14

Mesplede T, Quashie PK, Hassounah S, Osman N, Han Y, Liang J, Singhroy DN, Wainberg MA. The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. AIDS. 2015;29(12):1459-66. PubMed PMID: 26244385. Epub 2015/08/06. doi: 10.1097/QAD.0000000000000752

Mesplede T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, Petropoulos CJ, Huang W, Wainberg MA. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013;10:22. PubMed PMID: 23432922. Pubmed Central PMCID: 3598531. Epub 2013/02/26. doi: 10.1186/1742-4690-10-22

Abram ME, Hluhanich RM, Goodman DD, Andreatta KN, Margot NA, Ye L, Niedziela-Majka A, Barnes TL, Novikov N, Chen X, Svarovskaia ES, McColl DJ, White KL, Miller MD. Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Antimicrob Agents Chemother. 2013;57(6):2654-63. PubMed PMID: 23529738. Pubmed Central PMCID: 3716146. Epub 2013/03/27. doi: 10.1128/AAC.02568-12

Anstett K, Fusco R, Cutillas V, Mesplede T, Wainberg MA. Dolutegravir-selected HIV-1 containing the N155H/R263K resistance substitutions does not acquire additional compensatory mutations under drug pressure that lead to higher level resistance and increased replicative capacity. J Virol. 2015. PubMed PMID: 26246578. Epub 2015/08/08. doi: 10.1128/JVI.01725-15

Anstett K, Mesplede T, Oliveira M, Cutillas V, Wainberg MA. Dolutegravir resistance mutation R263K cannot coexist in combination with many classical integrase inhibitor resistance substitutions. J Virol. 2015;89(8):4681-4. PubMed PMID: 25653436. Pubmed Central PMCID: 4442391. Epub 2015/02/06. doi: 10.1128/JVI.03485-14

Yoshinaga T, Kobayashi M, Seki T, Miki S, Wakasa-Morimoto C, Suyama-Kagitani A, Kawauchi-Miki S, Taishi T, Kawasuji T, Johns BA, Underwood MR, Garvey EP, Sato A, Fujiwara T. Antiviral characteristics of GSK1265744, an HIV integrase inhibitor dosed orally or by long-acting injection. Antimicrob Agents Chemother. 2015;59(1):397-406. PubMed PMID: 25367908. Pubmed Central PMCID: 4291378. Epub 2014/11/05. doi: 10.1128/AAC.03909-14

Kobayashi M, Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, Ferris R, Foster SA, Hazen RJ, Miki S, Suyama-Kagitani A, Kawauchi-Miki S, Taishi T, Kawasuji T, Johns BA, Underwood MR, Garvey EP, Sato A, Fujiwara T. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011;55(2):813-21. PubMed PMID: 21115794. Pubmed Central PMCID: 3028777. Epub 2010/12/01. doi: 10.1128/AAC.01209-10

Hazuda DJ, Young SD, Guare JP, Anthony NJ, Gomez RP, Wai JS, Vacca JP, Handt L, Motzel SL, Klein HJ, Dornadula G, Danovich RM, Witmer MV, Wilson KA, Tussey L, Schleif WA, Gabryelski LS, Jin L, Miller MD, Casimiro DR, Emini EA, Shiver JW. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science. 2004;305(5683):528-32. PubMed PMID: 15247437. Epub 2004/07/13. doi: 10.1126/science.1098632

Peterson CW, Haworth KG, Polacino P, Huang ML, Sykes C, Obenza WM, Repetto AC, Kashuba A, Bumgarner R, DeRosa SC, Woolfrey AE, Jerome KR, Mullins JI, Hu SL, Kiem HP. Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation. AIDS. 2015;29(13):1597-606. PubMed PMID: 26372270. Pubmed Central PMCID: 4572605. Epub 2015/09/16. doi: 10.1097/QAD.0000000000000702

Dobard C, Sharma S, Parikh UM, West R, Taylor A, Martin A, Pau CP, Hanson DL, Lipscomb J, Smith J, Novembre F, Hazuda D, Garcia-Lerma JG, Heneine W. Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors. Sci Transl Med. 2014;6(227):227ra35. PubMed PMID: 24622515. Epub 2014/03/14. doi: 10.1126/scitranslmed.3007701

Kenney J, Singer R, Derby N, Aravantinou M, Abraham CJ, Menon R, Seidor S, Zhang S, Gettie A, Blanchard J, Piatak M, Jr., Lifson JD, Fernandez-Romero JA, Zydowsky TM, Robbiani M. A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use. AIDS Res Hum Retroviruses. 2012;28(11):1476-84. PubMed PMID: 22737981. Pubmed Central PMCID: 3484818. Epub 2012/06/29. doi: 10.1089/AID.2012.0087

Cranage M, Sharpe S, Herrera C, Cope A, Dennis M, Berry N, Ham C, Heeney J, Rezk N, Kashuba A, Anton P, McGowan I, Shattock R. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 2008;5(8):e157; discussion e. PubMed PMID: 18684007. Pubmed Central PMCID: 2494562. Epub 2008/08/08. doi: 10.1371/journal.pmed.0050157

Choudhary SK, Rezk NL, Ince WL, Cheema M, Zhang L, Su L, Swanstrom R, Kashuba AD, Margolis DM. Suppression of human immunodeficiency virus type 1 (HIV-1) viremia with reverse transcriptase and integrase inhibitors, CD4+ T-cell recovery, and viral rebound upon interruption of therapy in a new model for HIV treatment in the humanized Rag2-/-{gamma}c-/- mouse. J Virol. 2009;83(16):8254-8. PubMed PMID: 19494021. Pubmed Central PMCID: 2715775. Epub 2009/06/06. doi: 10.1128/JVI.00580-09

Neff CP, Ndolo T, Tandon A, Habu Y, Akkina R. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model. PLoS One. 2010;5(12):e15257. PubMed PMID: 21203568. Pubmed Central PMCID: 3006206. Epub 2011/01/05. doi: 10.1371/journal.pone.0015257

Kovarova M, Swanson MD, Sanchez RI, Baker CE, Steve J, Spagnuolo RA, Howell BJ, Hazuda DJ, Garcia JV. A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges. J Antimicrob Chemother. 2016. PubMed PMID: 27002074. Epub 2016/03/24. doi: 10.1093/jac/dkw042

Garrido C, Villacian J, Zahonero N, Pattery T, Garcia F, Gutierrez F, Caballero E, Van Houtte M, Soriano V, de Mendoza C. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob Agents Chemother. 2012;56(6):2873-8. PubMed PMID: 22450969. Pubmed Central PMCID: 3370736. Epub 2012/03/28. doi: 10.1128/AAC.06170-11

Sichtig N, Sierra S, Kaiser R, Daumer M, Reuter S, Schulter E, Altmann A, Fatkenheuer G, Dittmer U, Pfister H, Esser S. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother. 2009;64(1):25-32. PubMed PMID: 19447792. Epub 2009/05/19. doi: 10.1093/jac/dkp153

Veselinovic M, Yang KH, Sykes C, Remling-Mulder L, Kashuba AD, Akkina R. Mucosal tissue pharmacokinetics of the integrase inhibitor raltegravir in a humanized mouse model: Implications for HIV pre-exposure prophylaxis. Virology. 2016;489:173-8. PubMed PMID: 26771889. Epub 2016/01/16. doi: 10.1016/j.virol.2015.12.014

Elvitegravir (Vitekta) for HIV. Med Lett Drugs Ther. 2016;58(1486):10-1. PubMed PMID: 26761343. Epub 2016/01/14.

Massud I, Martin A, Dinh C, Mitchell J, Jenkins L, Heneine W, Pau CP, Garcia-Lerma JG. Pharmacokinetic profile of raltegravir, elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques. J Antimicrob Chemother. 2015;70(5):1473-81. PubMed PMID: 25630643. Pubmed Central PMCID: 4398473. Epub 2015/01/30. doi: 10.1093/jac/dku556

Spreen W, Min S, Ford SL, Chen S, Lou Y, Bomar M, St Clair M, Piscitelli S, Fujiwara T. Pharmacokinetics, safety, and monotherapy antiviral activity of GSK1265744, an HIV integrase strand transfer inhibitor. HIV Clin Trials. 2013;14(5):192-203. PubMed PMID: 24144896. Epub 2013/10/23. doi: 10.1310/hct1405-192

Andrews CD, Heneine W. Cabotegravir long-acting for HIV-1 prevention. Curr Opin HIV AIDS. 2015;10(4):258-63. PubMed PMID: 26049951. Epub 2015/06/08. doi: 10.1097/COH.0000000000000161

Trezza C, Ford SL, Spreen W, Pan R, Piscitelli S. Formulation and pharmacology of long-acting cabotegravir. Curr Opin HIV AIDS. 2015;10(4):239-45. PubMed PMID: 26049948. Epub 2015/06/08. doi: 10.1097/COH.0000000000000168

Spreen WR, Margolis DA, Pottage JC, Jr. Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013;8(6):565-71. PubMed PMID: 24100877. Pubmed Central PMCID: 3815009. Epub 2013/10/09. doi: 10.1097/COH.0000000000000002

Johns BA, Kawasuji T, Weatherhead JG, Taishi T, Temelkoff DP, Yoshida H, Akiyama T, Taoda Y, Murai H, Kiyama R, Fuji M, Tanimoto N, Jeffrey J, Foster SA, Yoshinaga T, Seki T, Kobayashi M, Sato A, Johnson MN, Garvey EP, Fujiwara T. Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744). J Med Chem. 2013;56(14):5901-16. PubMed PMID: 23845180. Epub 2013/07/13. doi: 10.1021/jm400645w

Andrews CD, Spreen WR, Mohri H, Moss L, Ford S, Gettie A, Russell-Lodrigue K, Bohm RP, Cheng-Mayer C, Hong Z, Markowitz M, Ho DD. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science. 2014;343(6175):1151-4. PubMed PMID: 24594934. Pubmed Central PMCID: 4308974. Epub 2014/03/07. doi: 10.1126/science.1248707

Andrews CD, Yueh YL, Spreen WR, St Bernard L, Boente-Carrera M, Rodriguez K, Gettie A, Russell-Lodrigue K, Blanchard J, Ford S, Mohri H, Cheng-Mayer C, Hong Z, Ho DD, Markowitz M. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge. Sci Transl Med. 2015;7(270):270ra4. PubMed PMID: 25589630. Pubmed Central PMCID: 4449736. Epub 2015/01/16. doi: 10.1126/scitranslmed.3010298

Hurt CB, Sebastian J, Hicks CB, Eron JJ. Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012. Clin Infect Dis. 2014;58(3):423-31. PubMed PMID: 24145878. Pubmed Central PMCID: 3890334. Epub 2013/10/23. doi: 10.1093/cid/cit697

Cavalcanti Jde S, Ferreira JL, Guimaraes PM, Vidal JE, Brigido LF. High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen. J Antimicrob Chemother. 2015;70(3):926-9. PubMed PMID: 25386009. Epub 2014/11/12. doi: 10.1093/jac/dku439

Radzio J, Spreen W, Yueh YL, Mitchell J, Jenkins L, Garcia-Lerma JG, Heneine W. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge. Sci Transl Med. 2015;7(270):270ra5. PubMed PMID: 25589631. Epub 2015/01/16. doi: 10.1126/scitranslmed.3010297

Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539. PubMed PMID: 21988835. Pubmed Central PMCID: 3261699. Epub 2011/10/13. doi: 10.1038/msb.2011.75

Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J, Lopez R. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. 2010;38(Web Server issue):W695-9. PubMed PMID: 20439314. Pubmed Central PMCID: 2896090. Epub 2010/05/05. doi: 10.1093/nar/gkq313

McWilliam H, Li W, Uludag M, Squizzato S, Park YM, Buso N, Cowley AP, Lopez R. Analysis tool web services from the EMBL-EBI. Nucleic Acids Res. 2013;41(Web Server issue):W597-600. PubMed PMID: 23671338. Pubmed Central PMCID: 3692137. Epub 2013/05/15. doi: 10.1093/nar/gkt376

Hartmann K, Donath A, Beer B, Egberink HF, Horzinek MC, Lutz H, Hoffmann-Fezer G, Thum I, Thefeld S. Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms. Vet Immunol Immunopathol. 1992;35(1-2):167-75. PubMed PMID: 1363008. Epub 1992/12/01.

Auwerx J, Esnouf R, De Clercq E, Balzarini J. Susceptibility of feline immunodeficiency virus/human immunodeficiency virus type 1 reverse transcriptase chimeras to non-nucleoside RT inhibitors. Mol Pharmacol. 2004;65(1):244-51. PubMed PMID: 14722257. Epub 2004/01/15. doi: 10.1124/mol.65.1.244

Shimojima M, Miyazawa T, Ikeda Y, McMonagle EL, Haining H, Akashi H, Takeuchi Y, Hosie MJ, Willett BJ. Use of CD134 as a primary receptor by the feline immunodeficiency virus. Science. 2004;303(5661):1192-5. PubMed PMID: 14976315. Epub 2004/02/21. doi: 10.1126/science.1092124

Denton PW, Krisko JF, Powell DA, Mathias M, Kwak YT, Martinez-Torres F, Zou W, Payne DA, Estes JD, Garcia JV. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice. PLoS One. 2010;5(1):e8829. PubMed PMID: 20098623. Pubmed Central PMCID: 2809117. Epub 2010/01/26. doi: 10.1371/journal.pone.0008829

Sun Z, Denton PW, Estes JD, Othieno FA, Wei BL, Wege AK, Melkus MW, Padgett-Thomas A, Zupancic M, Haase AT, Garcia JV. Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med. 2007;204(4):705-14. PubMed PMID: 17389241. Pubmed Central PMCID: 2118553. Epub 2007/03/29. doi: 10.1084/jem.20062411

Nischang M, Sutmuller R, Gers-Huber G, Audige A, Li D, Rochat MA, Baenziger S, Hofer U, Schlaepfer E, Regenass S, Amssoms K, Stoops B, Van Cauwenberge A, Boden D, Kraus G, Speck RF. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1. PLoS One. 2012;7(6):e38853. PubMed PMID: 22719966. Pubmed Central PMCID: 3374767. Epub 2012/06/22. doi: 10.1371/journal.pone.0038853


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