AIDS and Cancer Virus Program

Biography

Brandon F. Keele, Ph.D., is a Principal Scientist/Principal Investigator in the AIDS and Cancer Virus Program (ACVP) at SAIC-Frederick at the National Cancer Institute and currently heads both the Retroviral Evolution Section and Viral Evolution Core. Dr. Keele obtained his Ph.D. at Brigham Young University while studying the mechanism and diversity of virus trapping by follicular dendritic cells during HIV-1 infection. Dr. Keele previously worked at the University of Alabama at Birmingham first as a post-doctoral fellow and then as an Assistant Professor in the Department of Medicine. While as a post-doctoral fellow, Dr. Keele was the lead author describing the geographic origins of pandemic HIV-1. Recently, Dr. Keele and colleagues discovered that SIVcpz infecting chimpanzees was pathogenic and can lead to significant population decline. In collaboration with the Center for HIV/AIDS Vaccine Immunology (CHAVI), Dr. Keele utilized a novel limiting dilution PCR to elucidate the viral dynamics of transmission and early diversification in HIV-1 infected humans. Early sampling and these techniques allowed for the discovery that the vast majority of HIV-1 infections occur due to a single founder virus that can be unambiguously identified and studied. Dr. Keele established the Viral Evolution Core within the ACVP to expand our understanding of transmission and prevention using nonhuman primate models.

Research Description for Retroviral Evolution Section (RES)

The Retroviral Evolution Section (RES) studies various aspects of retroviral transmission, evolution, and immune evasion using sequencing, genetic analyses and molecular biology approaches to better understand the natural course of infection and potential sites and mechanisms of intervention. Dr. Keele¹s laboratory utilizes various nonhuman primate models of AIDS and newly generated viruses to better understand viral/host interactions.

Core Description

The Viral Evolution Core provides expertise and innovative sequencing techniques, molecular cloning, as well as viral evolution analyses to support extramural and intramural investigators in order to increase the overall understanding of viral transmission and early viral diversification, with a major focus on exploiting the unique advantages afforded by utilizing non-human primate models. Currently the VEC utilizes single genome amplification (SGA) and deep sequencing approaches (including 454 and SMRT technologies) to identify minor changes in viral populations. These approaches have been used to develop mucosal transmission models where most animals are infected with one for few variants thereby recapitulating HIV-1 infection in humans. These include rectal, vaginal and penile models of transmission. Furthermore, the VEC is utilizing these same approaches to help establish the efficacy of preventative measures including vaccines, microbicides, and passive administered neutralizing antibodies. Recently, Dr. Keele has pioneered an innovative approach to isolate and sequence viral RNA and DNA directly from HIV/SIV infected tissue as well as from individual cells/sections that are isolated by laser capture microdissection. These assays are currently being utilized to pinpoint the exact conditions and events surrounding viral transmission in nonhuman primates.

Recent Publications

1. Xiao P, Patterson LJ, Kuate S, Brocca-Cofano E, Thomas MA, Venzon D, Zhao J, Dipasquale J, Fenizia C, Lee EM, Kalisz I, Kalyanaraman VS, Pal R, Montefiori D, Keele BF, Robert-Guroff M. Replicating adenovirus-SIV recombinant priming and envelope protein boosting elicits localized, mucosal IgA immunity in rhesus macaques correlated with delayed acquisition following a repeated low dose rectal SIVmac251 challenge. J Virol Epub Feb 15 2012
2. Bolton DL, Song K, Wilson RL, Kozlowski PA, Tomaras GD, Keele BF, Lovingood RV, Rao S, Roederer M. Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge. Mucosal Immunol. 2012 Jan;5(1):41-52. PMID: 22031182.
3. Ochsenbauer C, Edmonds TG, Ding H, Keele BF, Decker J, Salazar MG, Salazar-Gonzalez JF, Shattock R, Haynes BF, Shaw GM, Hahn BH, Kappes JC. Genertaion of Transmitted/Founder HIV-1 Infectious Molecular Clones and Characterization of their Replication Capacity in CD4 T-Lymphocytes and Monocyte-derived Macrophages. J Virol. 2011 Dec 21.
4. Fenizia C, Keele BF, Nichols D, Cornara S, Binello N, Vaccari M, Pegu P, Robert-Guroff M, Ma ZM, Miller CJ, Venzon D, Hirsch V, Franchini G. TRIM5α does not affect simian immunodeficiency virus SIV(mac251) replication in vaccinated or unvaccinated Indian rhesus macaques following intrarectal challenge exposure. J Virol. 2011 Dec;85(23):12399-409. PMID: 21917950.
5. Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, Moldt B, Dunlop CC, Poignard P, Doyle LA, Cavacini L, Veazey RS, Moore JP. Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc Natl Acad Sci USA. 2011 Jul 5;108(27):11181-6. PMID:21690411.
6. Ma Z-M, 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 SIV env variant found in ramp-up phase plasma. AIDS Res Hum Retroviruses. 2011 Dec;27(12):1259-69. PMID:21732792.
7. Pandrea I, Gaufin T, Gautam R, Kristoff J, Mandell D, Montefiori D, Keele BF, Ribeiro RM, Veazey RS, Apetrei C. Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion. PLoS Pathog. 2011 Aug;7(8):e1002170. PMID:21829366.
8. Asmal M, Hellmann I, Liu W, Keele BF, Perelson AS, Bhattacharya T, Gnanakaran S, Daniels M, Haynes BF, Korber BT, Hahn BH, Shaw GM, Letvin NL. A signature in HIV-1 envelope leader peptide associated with transition from acute to chronic infection impacts envelope processing and infectivity. PLoS One. 2011 Aug 6(8):e23673. PMID: 21876761.
9. Keele BF, Estes JD. Barriers to mucosal transmission of immunodeficiency viruses. Blood. 2011 Jul 28;118(4):839-46. PMID:21555745.
10. Liu J, Keele BF, Li H, Keating S, Norris PJ, Carville A, Mansfield KG, Tomaras GD, Haynes BF, Kolodkin-Gal D, Letvin NL, Hahn BH, Shaw GM, Barouch DH: Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys. J Virol 84(19):10406-10412, 2010. Epub 2010 Aug 4. PMID20686016
11. Fischer W, Ganusov VV, Giorgi EE, Hraber PT, Keele BF, Leitner T, Han CS, Gleasner CD, Green L, Lo CC, Nag A, Wallstrom TC, Wang S, McMichael AJ, Haynes BF, Hahn BH, Perelson AS, Borrow P, Shaw GM, Bhattacharya T, Korber BT: Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PLoS One Aug 20;5(8):e12303, 2010. PMID:20808830
12. Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD, Keele BF, Ndjango JB, Sanz CM, Morgan DB, Locatelli S, Gonder MK, Kranzusch PJ, Walsh PD, Delaporte E, Mpoundi-Ngole E, Georgiev AV, Muller MN, Shaw GM, Peeter M, Sharp PM, Rayner JC, Hahn BH. Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature 467:420-425, 2010.
13. Yeh WW, Rahman I, Hraber P, Coffey RT, Nevidomskyte D, Giri A, Asmal M, Miljkovic S, Daniels M, Whitney JB, Keele BF, Hahn BH, Korber BT, Shaw GM, Seaman MS, Letvin NL: Autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys. J Virol 84(12):6018-6032, 2010. Epub 2010 Mar 31. PMID: 20357097
14. Keele BF: Identifying and characterizing recently transmitted viruses. Curr Opin HIV AIDS 5(4):327-334, 2010. PMID 20543609
15. Stone M, Keele BF, Ma ZM, Bailes E, Dutra J, Hahn BH, Shaw GM, Miller CJ: A limited number of SIVenv variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol 84(14):7083-7095, 2010. Epub 2010 May 12. PMID: 20463069
16. Keele BF, Derdeyn CA: Genetic and antigenic features of the transmitted virus. Current Opinion in HIV and AIDS 4:352-357, 2009. PMID: 20048697.
17. Salazar-Gonzalez JF, Salazar MG, Keele BF, Learn GH, Giorgi EE, Li H, Decker JM, Wang S, Baalwa J, Kraus MH, Parrish NF, Shaw KS, Guffey MB, Bar KJ, Davis KD, Ochsenbauer-Jambor C, Kappes JC, Saag MS, Cohen MS, Derdeyn CA, Allen S, Hunter E, Markowitz M, Hraber, P, Perelson AS, Bhattacharya T, Haynes BF, Korber BT, Hahn BH, Shaw GM: Genetic identity, biological phenotype and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med 206(6)1273-1289, 2009. Epub 2009 Jun 1. PMID: 19487424
18. 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 460:515-519, 2009. PMID: 19626114
19. 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 206(5):1117-1134, 2009. Epub 2009 May 1. PMID: 19414559
20. Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, Bett AJ, Liang X, Wang F, Thoryk E, Heidecker GJ, Cirton MR, Huang L, Lin J, Vitelli S, Ahn CD, Kaizu M, Maness NJ, Reynolds MR, Friedrich TC, Loffredo JT, Rakasz EG, Erickson S, Allison DB, Piatak MJr, Lifson JD, Shiver JW, Casimiro DR, Shaw GM, Hahn BH, Watkins DI: Vaccine-induced cellular responses control SIV replication after heterologous challenge. J Virol 83:6508-6521, 2009. PMID: 19403685
21. Lee HY, Giorgi EE, Keele BF, Gaschen B, Athreya GS, Salazar-Gonzalez JF, Pham KT, Goepfert PA, Michael Kilby J, Saag MS, Delwart EL, Busch MP, Hahn BH, Shaw GM, Korber BT, Bhattacharya T, Perelson AS: Modeling sequence evolution in acute HIV-1 infection. J Theor Biol 261(2):341-360, 2009. Epub 2009 Aug 4. PMID: 19660475.
22. Goonetilleke N, Liu MK, Gonzalez-Salazar JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, CHAVI Clinical Core B, Letvin NL. Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ: The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206(6):1253-1272, 2009. Epub 2009 Jun 1. PMID: 19487423
23. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 105:7552-7, 2008. PMCID2387184
24. Keele BF, Van Heuverswyn F, Li Y, Bailes E, Takehisa J, Santiago ML, Bibollet-Ruche F, Chen Y, Wain LV, Liegeois F, Loul S, Ngole EM, Bienvenue Y, Delaporte E, Brookfield JF, Sharp PM, Shaw GM, Peeters M, Hahn BH: Chimpanzee reservoirs of pandemic and non-pandemic HIV-1. Science. 2006 313:523-526. PMCID2442710

Staffing - Retroviral Evolution Section

• Carolyn Reid, Research Associate II
• Christine Fennessey, Post-doctoral Fellow

Staffing - Viral Evolution Core

• Laura Kreis, Research Associate I