Photo of Dr. Keele

Brandon F. Keele, Ph.D.

PI/Principal Investigator, Retroviral Evolution Section
Head, Viral Evolution Core

Leidos Biomedical Research, Inc.
Frederick National Laboratory for Cancer Research
Frederick, MD 21702-1201

Tel: 301-846-1731
Fax: 301-846-5588
Email: keelebf@mail.nih.gov

Biography

Brandon F. Keele, Ph.D., is a Principal Investigator/Principal Scientist in the AIDS and Cancer Virus Program (ACVP) at the Frederick National Laboratory for Cancer Research and currently heads both the Retroviral Evolution Section and the Viral Evolution Core. Dr. Keele obtained his Ph.D. at Brigham Young University while studying the mechanism and diversity of virus trapped by follicular dendritic cells during HIV-1 infection. Dr. Keele then 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 with Dr. Beatrice Hahn, Dr. Keele was the lead author describing the geographic origins of pandemic HIV-1. Dr. Keele and colleagues then discovered that SIVcpz is pathogenic to chimpanzees and can lead to significant population decline. In collaboration with Dr. George Shaw and 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 transmitted founder virus that can be unambiguously identified and studied. Dr. Keele established the Retroviral Evolution Section and the Viral Evolution Core within the ACVP to expand our understanding of transmission, viral evolution, eradication and vaccine-elicited prevention using nonhuman primate models.

Research Description for Retroviral Evolution Section

The Retroviral Evolution Section (RES) utilizes cutting edge technology to solve challenging and complex research questions in HIV/AIDS research with an emphasis in nonhuman primate models and SIV. The Retroviral Evolution Section studies viral transmission and subsequent evolution, as well as viral reservoir establishment/maintenance as a basis for HIV Cure research. We utilize sequencing, genetic analyses, and molecular biology to better understand both the natural course of infection and potential sites and mechanisms of intervention. Recently, using MRI and visual dyes, Dr. Keele has defined the likely routes of virus spread from sites of mucosal challenge through local draining lymphatics. Further, Dr. Keele has focused on characterizing viral stocks for use in NHP models. Specifically Dr. Keele has recently demonstrated that transfection-produced virus has fewer cytokines but also less Env compared to infection-produced stocks, which may explain the in vivo infectivity differences between the two methods of virus production. Dr. Keele has since expanded the characterization of infectious stocks to generating synthetic swarms using both a molecularly tag approach as well as novel approach which inserts a genetic barcode within the actual viral genome. These SIV stocks are being used to track individual viral variants during acute infection and to determine the timing and persistence of long-lived viral reservoirs.

Viral Evolution Core Description

The Viral Evolution Core (VEC) 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, early viral diversification, immune selection, genetic adaptation to new hosts, preclinical vaccine efficacy, and viral eradication with a major focus on exploiting the unique advantages afforded by utilizing non-human primates and SIV infection. Currently the VEC utilizes single genome amplification (SGA) and deep sequencing approaches (including Illumina, 454,and SMRT sequencing technologies) to identify genetic changes in viral populations. These approaches have helped develop mucosal transmission models where most animals are infected with one or a 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. Further, we have helped develop and characterize several divergent SIV, SHIV, and stHIV viruses for NHP research. Dr. Keele has also 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. Del Prete GQ, Ailers B, Moldt B, Keele BF, Estes JD, Rodriguez A, Sampias M, Oswald K, Fast R, Trubey CM, Chertova E, Smedley J, LaBranche CC, Montefiori DC, Burton DR, Shaw GM, Markowitz M, Piatak M Jr, KewalRamani VN, Bieniasz PD, Lifson JD, Hatziioannou T: Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins. Cell Host Microbe 16(3):412-418, 2014. doi: 10.1016/j.chom.2014.08.003. PMID: 25211081
  2. Matsuda K, Dang Q, Brown CR, Keele BF, Wu F, Ourmanov I, Goeken R, Whitted S, Riddick N, Buckler-White A, Hirsch VM: Characterization of SIV that induces SIV encephalitis in rhesus macaques with high frequency: Role of TRIM5 and MHC genotype and early entry to the brain. J Virol. 2014 Sep 3. pii: JVI.01996-14. [Epub ahead of print] PMID: 25187546
  3. Del Prete GQ, Shoemaker R, Oswald K, Lara A, Trubey CM, Fast R, Schneider DK, Kiser R, Coalter V, Wiles A, Wiles R, Freemire B, Keele BF, Estes JD, Quiñones OA, Smedley J, Macallister R, Sanchez RI, Wai JS, Tan CM, Alvord WG, Hazuda DJ, Piatak M Jr, Lifson JD: Effect of SAHA administration on the residual virus pool in a model of combination antiretroviral therapy-mediated suppression in SIVmac239-infected Indian rhesus macaques. Antimicrob Agents Chemother. 2014 Sep 2. pii: AAC.03746-14. [Epub ahead of print] PMID: 25182644
  4. Sandler NG, Bosinger SE, Estes JD, Zhu RT, Tharp GK, Boritz E, Levin D, Wijeyesinghe S, Makamdop KN, Del Prete GQ, Hill BJ, Timmer JK, Reiss E, Yarden G, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Norgren Jr RB, Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G, Douek DC: Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511(7511):601-605, 2014. Epub 2014 Jul 9. PMID: 25043006
  5. Hatziioannou T, Del Prete GQ, Keele BF, Estes JD, McNatt MW, Bitzegeio J, Raymond A, Rodriguez A, Schmidt F, Mac Trubey C, Smedley J, Piatak M Jr, KewalRamani VN, Lifson JD, Bieniasz PD: HIV-1 induced AIDS in monkeys. Science 344(6190):1401-1405, 2014. doi: 10.1126/science.1250761. PMID: 24948736
  6. Sui Y, Hogg A, Wang Y, Frey B, Yu H, Xia Z, Venzon D, McKinnon K, Smedley J, Gathuka M, Klinman D, Keele BF, Langermann S, Liu L, Franchini G, Berzofsky JA: Vaccine-induced myeloid cell population dampens protective immunity to SIV. J Clin Invest 124(6):2538-2549, 2014. doi: 10.1172/JCI73518. Epub 2014 May 16. PMID: 24837435
  7. Del Prete GQ, Park H, Fennessey CM, Reid C, Lipkey L, Lewman L, Oswald K, Kahl C, Piatak M Jr, Quinones OA, Alvord WG, Smedley J, Estes JD, Lifson JD, Picker LJ, Keele BF: Molecularly tagged SIVmac239 synthetic swarm for tracking independent infection events. J Virol 88(14):8077-8090, 2014. doi: 10.1128/JVI.01026-14. Epub 2014 May 7. PMID: 24807714
  8. Mandell DT, Kristoff J, Gaufin T, Gautam R, Ma D, Sandler N, Haret-Richter G, Xu C, Aamer H, Dufour J, Trichel A, Douek DC, Keele BF, Apetrei C, Pandrea I: Pathogenic features associated with increased virulence upon Simian Immunodeficiency Virus cross-species transmission from natural hosts. J Virol 88(12):6778-6792, 2014. Epub 2014 Apr 2. PMID: 24696477
  9. Smedley J, Turkbey IB, Bernardo ML, Del Prete GQ, Estes JD, Griffiths GL, Kobayashi H, Choyke PL, Lifson JD, Keele BF: Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission. PLoS One 9(3):e92830, 2014. doi: 10.1371/journal.pone.0092830. eCollection 2014. PMID: 24667371
  10. Hsu M, Keele BF, Aravantinou M, Krawczyk N, Seidor S, Abraham CJ, Zhang S, Rodriguez A, Kizima L, Derby N, Gettie A, Blanchard J, Piatak M Jr, Lifson JD, Fernandez-Romero JA, Zydowsky TM, Robbiani M: Exposure to MIV-150 from a high-dose intravaginal ring results in limited selection of drug resistance mutations in SHIV-RT infected rhesus macaques. PLoS One 9(2):e89300, 2014. doi: 10.1371/journal.pone.0089300. eCollection 2014. PMID: 24586674
  11. Roederer M, Keele BF, Schmidt SD, Mason RD, Welles HC, Fischer W, Labranche C, Foulds KE, Louder MK, Yang Z-Y, Todd J-PM, Buzby AP, Mach LV, Shen L, Seaton KE, Ward BM, Bailer RT, Gottardo R, Gu W, Ferrari G, Alam SM, Denny TN, Montefiori DC, Tomaras GD, Korber BT, Nason MC, Seder RA, Koup RA, Letvin NL, Rao SS, Nabel GJ, Mascola J: Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature 505(7484):502-508, 2014. doi: 10.1038/nature12893. Epub 2013 Dec 18. PMID: 24352234
  12. Van Rompay KK, Hunter Z, Jayashankar K, Peabody J, Montefiori D, LaBranche CC, Keele BF, Jensen K, Abel K, Chackerian B: A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with SIVmac251. J Virol 88(4):2011-2024, 2014. doi: 10.1128/JVI.02447-13. Epub 2013 Dec 4. PMID: 24307581
  13. Breed MW, Jordan AP, Aye PP, Sugimoto C, Alvarez X, Kuroda MJ, Pahar B, Keele BF, Hoxie JA, Lackner AA: A single amino acid mutation in the envelope cytoplasmic tail restores the ability of an attenuated simian immunodeficiency virus mutant to deplete mucosal CD4+ T cells. J Virol 87(23):13048-13052, 2013. doi: 10.1128/JVI.02126-13. Epub 2013 Sep 11. PMID: 24027336
  14. Hansen SG, Piatak M Jr, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Oswald K, Shoemaker R, Li Y, Lewis MS, Gilliam AN, Xu G, Whizin N, Burwitz BJ, Planer SL, Turner JM, Legasse AW, Axthelm MK, Nelson JA, Fruh K, Sacha JB, Estes JD, Keele BF, Edlefsen PT, Lifson JD, Picker LJ: Immune clearance of highly pathogenic SIV infection. Nature 502(7469):100-104, 2013. DOI: 10.1038/nature12519. PMID: 24025770. Published: 2013-09-01
  15. Fennessey C, Keele BF: Using nonhuman primates to model HIV transmission. Curr Opin HIV AIDS 8(4):280-287, 2013. doi: 10.1097/COH.0b013e328361cfff. PMID: 23666391
  16. Sundararaman SA, Liu W, Keele BF, Learn GH, Bittinger K, Mouacha F, Ahuka-Mundeke S, Manske M, Sherrill-Mix S, Li Y, Malenke JA, Delaporte E, Laurent C, Ngole EM, Kwiatkowski DP, Shaw GM, Rayner JC, Peeters M, Sharp PM, Bushman FD, Hahn BH: Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria. Proc Natl Acad Sci U S A 110(17):7020-7025, 2013. doi: 10.1073/pnas.1305201110. Epub 2013 Apr 8. PMID:23569255
  17. Lopker M, Easlick J, Sterrett S, Decker JM, Barbian H, Learn G, Keele BF, Robinson JE, Li H, Hahn BH, Shaw GM, Bar KJ: Heterogeneity in neutralization sensitivities of viruses comprising the SIVsmE660 isolate and vaccine challenge stock. J Virol 87(10):5477-5492, 2013. doi: 10.1128/JVI.03419-12. Epub 2013 Mar 6. PMID:23468494
  18. Del Prete GQ, Scarlotta M, Newman L, Reid C, Parodi LM, Roser JD, Oswald K, Marx PA, Miller CJ, Desrosiers RC, Barouch DH, Pal R, Piatak M Jr, Chertova E, Giavedoni LD, O’Connor DH, Lifson JD, Keele BK: Comparative characterization of transfection- and infection –derived SIV challenge stocks for in vivo non-human primate studies. J Virol 87(8):4584-4595, 2013, doi: 10.1128/JVI.03507-12. Epub 2013 Feb 13. PMID: 23408608
  19. Patel V, Jalah R, Kulkarni V, Valentin A, Rosati M, Alicea C, von Gegerfelt A, Huang W, Guan Y, Keele BF, Bess JW Jr, Piatak M Jr, Lifson JD, Williams WT, Shen X, Tomaras GD, Amara RR, Robinson HL, Johnson W, Broderick KE, Sardesai NY, Venzon DJ, Hirsch VM, Felber BK, Pavlakis GN: DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. PNAS 110(8):2975-2980, 2013. doi: 10.1073/pnas.1215393110. Epub 2013 Jan 28. PMID: 23359688
  20. Vaccari M, Keele BF, Bosinger SE, Doster M, Ma ZM, Pollara J, Hryniewicz A, Ferrari G, Guan YJ, Forthal D, Venzon D, Fenizia C, Morgan T, Montefiori D, Lifson JD, Miller C, Silvestri G, Rosati M, Felber BK, Pavlakis GN, Tartaglia J, Franchini G: Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 challenge exposure. J Virol 87(6):3538-3548, 2013. doi: 10.1128/JVI.02863-12. Epub 2013 Jan 16. PMID: 23325681
  21. Breed MW, Jordan AP, Aye PP, Lichtveld CF, Midkiff C, Schiro FR, Haggarty BS, Sugimoto C, Alvarez X, Sandler NG, Douek DC, Kuroda MJ, Pahar B, Piatak M Jr, Lifson JD, Keele BF, Hoxie JA, Lackner AA: Loss of a tyrosine-dependent trafficking motif in the SIV envelope cytoplasmic tail spares mucosal CD4 cells but does not prevent disease progression. J Virol 87(3):1528-1543, 2013 doi: 10.1128/JVI.01928-12. Epub 2012 Nov 14. PMID: 23152518
  22. Pegu P, Vaccari M, Gordon S, Keele BF, Doster M, Guan Y, Ferrari G, Pal R, Ferrari MG, Whitney S, Hudacik L, Billings E, Rao M, Montefiori D, Tomaras G, Alam SM, Fenizia C, Lifson JD, Stablein D, Tartaglia J, Michael N, Kim J, Venzon D, Franchini G: Antibodies with high avidity to the gp120 envelope protein in protection from SIVmac251 acquisition in an immunization regimen that mimics the RV-144 Thai Trial. J Virol 87(3):1708-1719, 2013. doi: 10.1128/JVI.02544-12. Epub 2012 Nov 21. PMID: 23175374
  23. Breed MW, Jordan AP, Aye PP, Sugimoto C, Alvarez X, Kuroda MJ, Pahar B, Keele BF, Hoxie JA, Lackner AA: A single amino acid mutation in the envelope cytoplasmic tail restores the ability of an attenuated simian immunodeficiency virus mutant to deplete mucosal CD4+ T cells. J Virol 87(23):13048-13052, 2013. doi: 10.1128/JVI.02126-13. Epub 2013 Sep 11. PMID: 24027336
  24. Baalwa J, Wang S, Parrish NF, Decker JM, Keele BF, Learn GH, Yue L, Ruzagira E, Ssemwanga D, Kamali A, Amornkul PN, Price MA, Kappes JC, Karita E, Kaleebu P, Sanders E, Gilmour J, Allen S, Hunter E, Montefiori DC, Haynes BF, Cormier E, Hahn BH, Shaw GM: Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones. Virology 436(1):33-48, 2013. doi: 10.1016/j.virol.2012.10.009. Epub 2012 Nov 1. PMID: 23123038
  25. Li Y, Ndjango JB, Learn GH, Ramirez MA, Keele BF, Bibollet-Ruche F, Liu W, Easlick JL, Decker JM, Rudicell RS, Inogwabini BI, Ahuka-Mundeke S, Leendertz FH, Reynolds V, Muller MN, Chancellor RL, Rundus AS, Simmons N, Worobey M, Shaw GM, Peeters M, Sharp PM, Hahn BH: Eastern chimpanzees, but not bonobos, represent a simian immunodeficiency virus reservoir. J Virol 86(19):10776-10791, 2012. doi: 10.1128/JVI.01498-12. Epub 2012 Jul 25. PMID: 22837215
  26. Bar KJ, Tsao CY, Iyer SS, Decker JM, Yang Y, Bonsignori M, Chen X, Hwang KK, Montefiori DC, Liao HX, Hraber P, Fischer W, Li H, Wang S, Sterrett S, Keele BF, Ganusov VV, Perelson AS, Korber BT, Georgiev I, McLellan JS, Pavlicek JW, Gao F, Haynes BF, Hahn BH, Kwong PD, Shaw GM: Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape. PLoS Pathog 8(5):e1002721, 2012. Epub 2012 May 31. PMID: 2693447
  27. Gautam R, Nishimura Y, Lee WR, Donau O, Buckler-White A, Shingai M, Sadjadpour R, Schmidt SD, Labranche CC, Keele BF, Montefiori D, Mascola JR, Martin MA: Pathogenicity and mucosal transmissibility of R5-tropic Simian/Human Immunodeficiency Viruses SHIVAD8 in rhesus macaques: Implications for their use in vaccine studies. J Virol 86(16):8516-8526, 2012. Epub 2012 May 30. PMID: 22647691
  28. Bibollet-Ruche F, Heigele A, Keele BF, Easlick JL, Decker JM, Takehisa J, Learn G, Sharp PM, Hahn BH, Kirchhoff F: Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation. J Clin Invest 122(5):1644-1652, 2012. doi: 10.1172/JCI61429. Epub 2012 Apr 16. PMID: 22505456
  29. Wu X, Wang C, O'Dell S, Li Y, Keele BF, Yang Z, Imamichi H, Doria-Rose N, Hoxie JA, Connors M, Shaw GM, Wyatt RT, Mascola JR: Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the conserved CD4-binding site. J Virol 86(10):5844-5856, 2012. Epub 2012 Mar 14. PMID: 22419808
  30. 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 86(8):4644-4657, 2012. Epub 2012 Feb 15 PMID: 22345466
  31. 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: Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T-lymphocytes and monocyte-derived macrophages. J Virol 86(5):2715-2728, 2012. Epub 2011 Dec 21. PMID: 22190722
  32. Del Prete GQ, Kearney MF, Spindler J, Wiegand A, Chertova E, Roser JD, Estes JD, Hao XP, Trubey CM, Lara A, Lee K, Chaipan C, Bess JW Jr, Nagashima K, Keele BF, Pung R, Smedley J, Pathak VK, Kewalramani VN, Coffin JM, Lifson JD: Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques. J Virol 86(6):3152-3166, 2012. Epub 2012 Jan 11. PMID: 22238316

Staffing – Retroviral Evolution Section

  • Sean P. O'Brien, Ph.D., Postdoctoral Fellow
  • Carolyn Reid, Research Associate II

Staffing – Viral Evolution Core

  • Laura Newman – Research Associate I