Associate Professor
Department of Microbiology and Immunology
Jacobs School of Medicine & Biomedical Sciences
Infectious Disease; Molecular and Cellular Biology; Transgenic organisms; Viral Pathogenesis; Virology
Retroviruses comprise a large and diverse family of RNA viruses that can infect a variety of hosts and can lead to immune system dysfunction and cancer. The most well known member of this family is HIV (Human Immunodeficiency Virus), which is responsible for millions of deaths every year. Immune cells, such as CD4+ T cells, are the targets of HIV infection resulting in their subsequent destruction and the overall impairment of the immune system. As a result of the deterioration of the immune system, the host is unable to fight effectively infections and some other diseases. Opportunistic infections or cancers take advantage of the weakened host, which can prove to be lethal. Other members of the retrovirus family, Murine Leukemia Virus (MLV) and Mouse Mammary Tumor Virus (MMTV) are common pathogens of mice that are used in research to study the interplay between the host and retroviruses and have served as models for HIV and other human retroviruses.
In the context of the constant struggle between host cells and pathogens, cells have developed early innate immune and cell-intrinsic strategies to counteract retroviruses. Therefore, retroviruses have developed a variety of sophisticated mechanisms to counteract cellular responses and allow for productive infections to occur. Due to the complexity of the antiviral immune response, a full understanding of host-pathogen interactions requires the integration of in vitro and in vivo data, where the role of cellular restriction factors and the innate immune response are examined in a living organism. Infections in mouse models have provided important and at times surprising insights into the relationship between hosts and pathogens. Thus one of the areas of focus for our lab will be the integration of in vivo and in vitro models to study the interaction of novel cellular host factors and retroviruses.
HIV and other lentiviruses devote a relatively large portion of their genome to accessory proteins that counteract those cellular host factors. Understanding the function of these accessory proteins has provided insight into the intrinsic defenses utilized by the cell to block viral infections, as well as generated potential targets for antiviral interventions. However, there is no currently tractable in vivo model for studying cell host restriction factor/accessory protein interactions. Hence, the second major focus of our lab will be the development of in vivo models to examine the interplay between HIV accessory proteins and host cell intrinsic immunity.