AIDS and Cancer Virus Program
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
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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Keele BF, Estes JD. Barriers to mucosal transmission of immunodeficiency
viruses. Blood. 2011 Jul 28;118(4):839-46. PMID:21555745.
- 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
- 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
- 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,
- 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
- Keele BF: Identifying and characterizing recently transmitted viruses. Curr Opin
HIV AIDS 5(4):327-334, 2010. PMID 20543609
- 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
- Keele BF, Derdeyn CA: Genetic and antigenic features of the transmitted virus. Current
Opinion in HIV and AIDS 4:352-357, 2009. PMID: 20048697.
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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