The Viral Persistence Section seeks to better understand the establishment, maintenance, and consequences of persistent AIDS virus infections. 

To achieve these goals, we employ existing and novel nonhuman primate (NHP) models of HIV infection and our extensive experience in the administration and evaluation of antiretroviral agents in NHPs. With the support of the specialized expertise and infrastructure established within the AIDS and Cancer Virus Program’s research support cores, our work uses a combination of NHP models of HIV infection, along with advanced cell culture, virology, and molecular biology techniques to facilitate the development and evaluation of approaches to prevent and eliminate persistent viral reservoirs, including those within the central nervous system. 

HIV persists despite effective antiretroviral therapy

HIV establishes persistent sources of virus throughout the body early in infection. Because these viral reservoirs can persist despite decades of effective viral suppression with combination antiretroviral therapy, lifelong treatment is necessary to prevent the development of AIDS. Even with effective suppressive therapy, people with HIV are at increased risk of a variety of non-AIDS morbidities. The development of new approaches to prevent the establishment of persistent viral reservoirs, and to target and eliminate them once established, remains critically important.  

Emphasis on virus persistence in the context of the whole organism 

NHP models of HIV infection are relevant systems in which to study the complexities of viral infection and the mechanisms of viral persistence in various tissues throughout the body. Our laboratory has a longstanding interest in developing new NHP models tailored to address specific scientific questions that are difficult or impossible to study in humans. Since our initial description of a feasible combination antiretroviral therapy regimen that can suppress SIV and SIV-based viruses to clinically relevant levels in macaques, we have continued to specialize in the use and evaluation of antiretroviral agents and other drugs in NHP models of HIV to prevent infection, to suppress infection, and to enable research as tools to reveal new insights about viral biology and persistence. 

Collaboration Opportunities

AIDS and Cancer Virus Program research sections and research support cores collaborate with scientists within and outside the National Institutes of Health to address key remaining challenges in the prevention and treatment of HIV infection and associated conditions. We engage with external investigators through partnership mechanisms, including Cooperative Research and Development Agreements (CRADAs), Material Transfer Agreements (MTAs), and Technical Service Agreement (TSAs).

Target cell depletion

Effectiveness of antibody-based approaches to eliminate viral reservoirs may be limited

Depletion is particularly limited in gut tissues, where most HIV/SIV target cells reside.
HIV capsid inhibitor

Lenacapavir shows potential for prevention of HIV infection

Study results support ongoing clinical development of long-acting pre-exposure prophylaxis (PrEP).

Development of new models to study viral reservoir formation within the central nervous system 

HIV can replicate within the central nervous system, raising the possibility that long-lived sources of virus may be formed in this anatomical compartment, which poses distinct challenges for efforts to eliminate persistent viral reservoirs. We are pursuing diverse avenues to develop new NHP models of HIV infection and reservoir formation in the CNS to understand how such sources of viruses are seeded and maintained and how we might target them for elimination. 

Nonhuman primate model development, characterization, and application 

We specialize in the development and in vivo evaluation of novel NHP models of HIV infection, with an emphasis on new chimeric viruses and studies involving antiretroviral agents. 

  • Simian-human immunodeficiency virus (SHIV) development

  • Simian-tropic HIV-1 (stHIV) development

  • CNS infection model development

  • Antiretroviral drug administration and assessment

  • Evaluation of proposed HIV cure strategies  

Virologic, immunologic, and molecular biology assays and techniques 

Our laboratory uses a suite of virologic, immunologic, and molecular biology assays and capabilities to facilitate our broader research objectives and to better understand the biology of AIDS virus infections. 

  • Infectious HIV/SIV/SHIV/stHIV production

  • In vitro virus growth and inhibition 

  • Mammalian cell culture and limiting dilution cloning 

  • PCR, RT-PCR, digital PCR 

  • ELISA 

  • Multiplexed serology assays 

  • Flow cytometry 

Epigenetic analyses 

Epigenetics is the study of modifications of DNA that help control gene expression. We developed epigenetic analytical methods to examine host cell gene regulation in NHP cells during different stages of AIDS virus infection. 

  • DNA methylation analyses (bisulfite sequencing, DNA methylation ELISA) 

  • Chromatin immunoprecipitation (ChIP)-PCR