We use molecular biology approaches to develop and employ novel viral systems to leverage the advantages of nonhuman primate models. Our work addresses critical questions in key areas of AIDS research, including transmission, adaptation, persistence, and evolution that allows the pathogen to evade eradication/cure strategies.  

Arresting the HIV viral reservoir 

A major barrier to curing HIV is the persistence of a rebound-competent viral reservoir (RCVR) in infected people. Combination antiretroviral therapy effectively suppresses viral replication and can help restore immune function, preventing disease progression, but as soon as the therapy is interrupted, uncontrolled viral replication can resume, with this viral rebound leading to disease progression if treatment is not restarted. To provide the best care to people living with HIV, it is therefore imperative to determine key aspects of how the virus is transmitted, establishes a rebound-competent reservoir, and evolves to evade host immune pressure and develop drug-resistance mutations. 

We develop specific viral models to answer critical questions in HIV 

Our laboratory focuses on using molecular biology approaches paired with nonhuman primate in vivo studies to address fundamental HIV biology questions that cannot be examined in humans living with HIV. By generating our own customized, molecularly engineered HIV/SIV viruses, we can fine-tune the variables queried in our in vivo studies, and home in on specific aspects of the virus-host battle. We then employ specialized sequencing techniques and advanced computational analysis to obtain the most robust and informative data possible.

Collaboration Opportunities

We welcome collaboration. Our custom viruses are available to the HIV/SIV research community.

We view science as best advanced when collaborations are established with an openness of communication, ideas, and data. Therefore we welcome the opportunity to share our expertise and resources with the greater scientific community. 

Contact Dr. Brandon Keele about collaborating.

Researcher Resource

Our research focuses on elucidating aspects of HIV transmission, dynamics, and cure  

Our laboratory has multiple ongoing studies that seek to uncover deeper insights into the mechanisms of HIV/SIV by using the barcoded virus paired with nonhuman primate animal models. One such study involves identifying the anatomic locations of the early viral reservoir by challenging with the barcoded virus, performing early acute phase necropsies, and sequencing each individual tissue to identify the resident virus barcode variants.

Additionally, we seek to better understand the role of the immune system in the systemic spread of the virus following vaginal transmission by treating animals with a lymphocyte trafficking inhibitor and subsequently challenging with our genetically tagged SIV. Finally, we employ advanced computational biology approaches to design improved model systems to test novel reservoir-reducing therapies by assessing the establishment and persistence of the reservoir in relation to acute infection and subsequent post-antiretroviral-therapy viral rebound.  

Furthering discoveries toward a deeper understanding of the fundamental biology of HIV and its cure 

Brandon Keele, Ph.D., and his team author high-impact manuscripts describing both internally driven and collaborative studies with investigators across the country. Our publications describe use of a diverse range of cutting-edge approaches that seek to identify biological avenues for improved treatment or cure of persons living with HIV.  

Our capabilities and specializations

Additional Content

Discovery of HIV fundamentals using molecular biology techniques 

We generate customized versions of HIV/SIV to address specific aspects of HIV biology for both in vivo and in vitro use.

Additional Content
  • Barcoded or genetically tagged SIV/HIV/SHIV/stHIV  

  • Fluorescently tagged SIV 

  • Molecularly optimized SIV 

  • CTL-escaped SIV 

  • Antigen-presenting SIV 

Additional Content

Applying computational biology to HIV 

We explore heretofore unknown aspects of HIV/SIV dynamics by generating computational models built around data generated in vivo.  

Additional Content
  • Post-ATI viral reactivation rates 

  • CTL escape mechanisms 

  • In vivo viral decay phases/rates 

  • Reservoir decay phases/rates 

Additional Content

Download the Barcode Analysis Tool

MiSeq BAF folder contains an R-script with associated support files to demultiplex next-generation sequencing and determine the abundance of individually barcoded SIV/SHIV viral lineages. Please read the Barcode Analysis Application User Guide, which is included in the folder, prior to starting. 

MiSeq Env folder contains an R-script to determine the abundance of two regions of the Envelope Glycoprotein in SIVmac239 following amplicon sequencing. 

For questions, please email Brandon Keele, Ph.D., at keelebf@mail.nih.gov.

surface model of the non-glycosylated CH505 SOSIP Env trimer, PDB ID 6vy2
Study showcase

Development of improved SHIV for NHP models

SHIVs—chimeric viruses that are comprised of parts of HIV grafted onto an SIV “backbone”-- are essential reagents for NHP models of HIV as in contrast to wild type HIV they can replicate well in macaques, but contain an HIV envelope to allow for testing of therapeutic antibodies or drugs that target this key HIV protein. This paper describes the introduction of five-point mutations into the SHIV genome to improve its replication in vivo, making it a more useful model virus for studies focused on transmission, pathogenesis, and cure.
RNAscope image of MesLN
Study Spotlight

Use of the barcoded virus to identify sites of viral recrudescence

The major obstacle to HIV cure is the establishment of a rebound competent viral reservoir during early acute infection. The presence of this reservoir guarantees the recrudescence of systemic viremia if ART is interrupted in a person living with HIV. Therefore, it is essential to identify the anatomical sites that contribute to the viral rebound so that targeted treatments may be developed to impede this reactivation. This study seeks to identify these sites using the barcoded virus model and corresponding analytical pipeline developed by our laboratory.