The Retroviral Pathogenesis Section conducts basic, applied, and translational research to understand retroviral disease mechanisms. We work with nonhuman primate (NHP) models, employing in vitro and in vivo approaches, and evaluate strategies to more effectively prevent and treat AIDS virus infections and their consequences. 

Our basic studies characterize fundamental processes and virus–host interactions relevant to viral pathogenesis, prevention, and treatment.  

Our applied and translational studies evaluate candidate vaccines and other prevention approaches, along with studies of novel drug and immunotherapeutic interventions to control viral replication and target the Rebound-Competent Viral Reservoir—virus that persists despite sustained suppressive antiretroviral drug treatment and can reignite a progressive systemic infection if treatment is stopped. 

Towards a cure for HIV infection 

People living with HIV require lifelong treatment due to the Rebound-Competent Viral Reservoir. We characterize the biology of how this virus is able to persist during extended antiretroviral treatment and evaluate approaches to target, reduce, or eliminate it. This work holds the potential to lead to more definitive treatment of AIDS virus infection that will eliminate the need for lifelong therapy. 

Collaboration Opportunities

Dr. Lifson and colleagues collaborate widely with scientists within and outside the National Institutes of Health to address remaining challenges in the prevention and treatment of HIV infection and associated conditions. In addition to academic-style collaborations, external investigators can work with us through multiple established formal collaboration mechanisms, including Cooperative Research and Development Agreements (CRADA), Material Transfer Agreements (MTA), and Technical Service Agreements (TSA).

Contact Dr. Jeffrey Lifson.

 

Preclinical models for evaluation of vaccine and treatment approaches 

We develop and apply NHP models to address key questions in AIDS research, exemplified by our development of a novel minimally chimeric, engineered form of HIV. While HIV itself does not replicate to high levels or cause disease in monkeys, our engineered and adapted HIV that is genetically 94% HIV replicates to high levels and can cause AIDS in experimental infection of pigtail macaques. We used this model to demonstrate that lenacapavir, a promising first-in-class antiretroviral drug that targets the HIV capsid (and is much less potent against other AIDS viruses that infect monkeys), is able to prevent infection in a stringent pre-exposure prophylaxis challenge study, providing preclinical proof-of-concept validation for the use of the drug in this setting. 

Our capabilities and specializations

NHP models 

Varied NHP models developed for the study of key aspects of AIDS virus pathogenesis.

  • Vaccine prevention of infection 

  • Non-vaccine prevention of infection 

  • Characterization of the Rebound-Competent Viral Reservoir (RCVR) 

  • Evaluation of strategies for targeting the RCVR 

  • Characterization of molecular aspects of virus–host cell interactions