Discoveries by AIDS researcher Brandon F. Keele, Ph.D. have not only put him on the leading edge of research to prevent and treat HIV infection. He’s also influenced the work of his peers.
Keele, a principal investigator and senior principal scientist in the AIDS and Cancer Virus Program at the Frederick National Laboratory was named a Highly Cited Researcher by Web of Science, a global citation database. Keele and colleague Jeffrey Lifson, M.D. were recognized for producing papers that ranked in the top 1 percent by citations for their field.
Keele published his first paper when he was a graduate student at Brigham Young University. It was the 2001 Journal of Immunology article, “Persistence of Infectious HIV on Follicular Dendritic Cells.”
Since then Keele, 47, has authored 163 papers which have been cited more than 17,000 times.
His most-referenced paper was published by Proceedings of the National Academy of Sciences in 2008 and is considered a seminal paper in the field. As a post-doc at the University of Alabama at Birmingham, Keele and his colleagues identified and described for the first time the viruses responsible for the transmission and establishment of a clinical HIV infection.
“Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection” was a game changer and literally sparked a new area of HIV research, focusing on the transmitter/founder viruses that start an infection. They are the viruses that must be blocked by an antibody or vaccine.
Prior to the discovery by Keele and colleagues, little was known about the genetic identity of HIV as it was transmitted from donor to recipient. “We were able to sample people early (following becoming infected) and with sequencing methods we still use today we could genetically identify each virus,” Keele said.
The paper is at 1,776 citations and climbing.
Mysterious Disease Sparked Scientific Intrigue and Action
Keele was in middle school in the 1980s when the AIDS crisis dominated the news. He recalled a boy from his town who acquired HIV through a blood transfusion. The boy’s appearance at a school assembly to tell his story sent panic through the student body. Keele was drawn to help figure out this new, important and perplexing disease. After high school he earned his undergraduate and graduate degrees at Brigham Young.
Keele’s post-doc work at the University of Alabama at Birmingham in 2006 yielded another “first” – a clear picture of the geographic origin of HIV and the seeds of the AIDS pandemic. His team traced the virus that infects humans to a distinct, geographically isolated chimpanzee community.
The paper, “Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1” was published in Science. It identified the wild-living P. t. troglodytes apes in southern Cameroon as the source of the virus.
The findings were based on studies of fecal samples collected in the jungle by hunters who were paid to stop hunting and instead track the animals and gather their droppings for research. Keele said the samples have been used by many HIV researchers. The paper has been cited 1,053 times, with new citations noted regularly.
Keele continues to study HIV transmission and how to block it, in rhesus macaques. His team has engineered simian/human immunodeficiency viruses (SHIVs) for HIV prevention and treatment studies. The SHIVs are engineered to imitate HIV as closely as possible for use in the laboratory models of the disease.
A New Tool to Track a Mutating Virus
His most recent paper demonstrates that tagging a virus with its own unique barcode makes it possible to measure the strength of the immune response against the virus and to what extent it mutates.
“Genetically Barcoded SIV Reveals the Emergence of Escape Mutations in Multiple Viral Lineages During Immune Escape,” was published in PNAS in December 2019.
Keele and colleagues attached a bar code – much like you’d find on the bottom of a cereal box – to more than 1,000 different lineages of simian immunodeficiency virus, an HIV-like virus that infects rhesus macaques. As each virus grew and mutated, it carried the unique genetic tag with it, allowing the team to track each viral lineage over time and in different tissues.
Previous studies by Keele and others show HIV infection is established by a single founder virus. As the immune system puts pressure on the virus, it rapidly mutates. Genetic barcoding allowed Keele and colleagues to quantify that pressure and determine how close the virus came to dying off.
Typically, researchers are only able to determine the activity of the collection of mutated viruses. Seeing what is happening to each individual virus provides a rich data set to support clinical trials that track the strength of antiretroviral drugs and vaccines. “You can see how close to extinction you can get,” Keele said.
The model is not specific for SIV and HIV. It could be used to assess the likelihood of eventual suppression of any virus.
“It gives you an idea of how effective a vaccine would have to be to eliminate a virus,” Keele said.Tagged: