Amitinder Kaur, MD
Assistant Professor
The New England Primate Research CenterAIDS pathogenesis and CMV opportunistic infection: SIV; vaccine; AIDS resistance
AIDS modeling in non-human primates; reactivation of latent CMV in HIV-infected individuals; innate resistance to SIV-related disease progression.
Commercial Opportunities
Address critical aspects of SIV pathogenesis that may pave the way for new therapies against HIV infection; test viral vectors for use in long-lasting HIV vaccines.
Twenty-five years after the identification of HIV, the agent responsible for causing AIDS, the outlook for developing a vaccine remains bleak, and current therapies can cause serious side-effects. Studying SIV infection in non-human primate models offers the best approach to studying molecular mechanisms of HIV infection and its corresponding host immune response in a controlled setting, and for yielding insights that should have significant commercial ramifications. Dr. Kaur’s laboratory is addressing critical aspects of SIV pathogenesis that may pave the way for new therapies. These investigations utilize unique animal models and research tools, such as, recombinant viral vectors and viral-encoded genes, not easily accessible to most companies. Therefore, the lab can be a valuable resource for companies to leverage for collaborative initiatives to advance AIDS therapeutics and vaccines. The lab’s work on testing novel viral vectors in an attenuated vaccine strategy may lead to long-lasting immunity, a key feature of a successful vaccine against HIV. Its studies on the effect of SIV on the reactivation of latent CMV offers great commercial potential for developing therapeutic intervention strategies to dampen reactivation and reduce the likelihood of morbidity associated with opportunistic infection.
Current Research Interests
AIDS modeling in non-human primates is perhaps the most promising avenue of research for sifting through the myriad of defenses that HIV/SIV have evolved to thwart eradication. The interplay between AIDS and opportunistic infection is also a critical component of AIDS sequelae. Reactivation of latent CMV in HIV-infected individuals can cause life-threatening infections, including pneumonia and retinitis. Dr. Kaur’s laboratory uses monkeys to investigate these aspects of HIV/SIV infection. An intriguing feature of this research pertains to studies of innate resistance to SIV-related disease progression in certain monkey species, such as sooty mangabeys, which remain asymptomatic despite viremia. These studies hold tremendous promise for pinpointing host factors that modulate viral pathogenesis.
- Explore the properties of a protective host immune response that can successfully counter the adverse consequences of the persistent infection characteristic of SIV/HIV.
- Continue investigations into new approaches for vaccine development, including the potential of novel, genetically-engineered viral vectors,such as recombinant herpes viruses, that incite long-lasting antiviral immune responses.
- Study the mechanisms of CMV reactivation in SIV-infected monkeys, with particular attention to the dampening effect of SIV on the CMV immune response.
- Investigate the effects of CD4+ T-lymphocytes on CMV-specific memory T-lymphocytes and priming of CD8+ T-lymphocytes because the hallmark of HIV/SIV infection is CD4+ T-lymphocyte depletion.
- Employ sooty mangabeys, a natural SIV host, as a model to study resistance to AIDS and analyze the mangabeys’ host T-lymphocyte response to SIV infection compared to species that succumb to SIV-dependent AIDS, such as macaques.
Research Expertise
Dr. Kaur’s laboratory uses non-human primate models to study AIDS pathogenesis. The lab focuses on the immune response to infection caused by the simian immunodeficiency virus (SIV), the closest known relative to HIV. Specific areas of research include: study of the basis of cytomegalovirus reactivation in HIV-infected individuals; nonpathogenic SIV infection in natural hosts; and vaccine-induced protective immunity against AIDS. In collaboration with David Knipe, the lab undertook an experimental approach to study the immune response of animals that were challenged with SIV after being exposed to an attenuated viral vector. Their work, which was recently published, demonstrated that a genetically engineered, replication-defective, herpes simplex virus can potently prime the immune system and elicit partial protective immunity against SIV infection. These findings are particularly exciting because herpes viruses remain infectious for the entire lifetime of its host and a primary deficiency in many vaccination strategies is the lack of persistent immunity.
The lab also studies the phenomenon of innate resistance to SIV-induced disease progression in sooty mangabeys, with the goal of understanding the host factors that define the AIDS disease course. Although sooty mangabeys are naturally infected with SIV, they typically do not exhibit any tell-tale signs of a compromised immune system, or any other manifestations of AIDS. The lab has begun to hone in on the functional aspects of the immune response in this species that might underlie its unusual refractoriness to AIDS. In recently published work, they found that sooty mangabeys did not show any increase in CD4+ T lymphocyte apoptosis or TNF-related apoptosis inducing ligand (TRAIL) after SIV infection. The controlled T lymphocyte activation might limit destruction of bystander immune cells and prevent the onset of AIDS.
Another long-standing research interest is the development of active CMV infection in HIV-infected individuals, a risk factor for developing full-blown AIDS. The lab has found that CMV-specific antibody and CD8+ T lymphocyte levels fall considerably in SIV-infected macaques that display CMV-related disease. This finding suggests an antagonistic effect of loss of CMV-specific CD4+ T-lymphocytes on other T- and B-lymphocyte populations.