Our group seeks to understand how viruses cause disease in humans. A better understanding of these mechanisms can lead to the development of vaccines to prevent new infections and anti-viral drugs to treat current infections. The lack of animal models that can be infected with human viruses and exhibit similar disease has seriously hampered these areas of research. In order to study viral infections of human cells in vivo, we use “humanized mice.” A humanized mouse is one in which human cells have been transplanted. We transplant mice with human hematopoietic stem cells; this leads to production of a variety of human blood cell types and development of a human immune system in the mouse. Antibody and cellular immune responses of human origin can then be generated in the mouse.
We are interested in studying viral pathogens that infect human blood cells in our humanized mice. Examples include Dengue Virus (DV), Human Immunodeficiency Virus (HIV), Human herpesvirus 6 (HHV-6), and Kaposi’s Sarcoma Herpesvirus (KSHV). DV infects approximately 100 million worldwide per year and the rate is rapidly increasing. Infection can lead to hemorrhagic fever and death, but no vaccines or antiviral are available. About 34 million people worldwide are HIV+, and millions die each year from complications due to AIDS. No vaccines exist, and although effective antiviral drugs are available, they have undesirable side effects and the virus can mutate to escape. One side effect of AIDS is HIV-associated lymphoma (cancer of white blood cells) which commonly arise in patients co-infected with gammaherpesviruses like KSHV. No vaccine is available for KSHV, and we have little understanding of how immunosuppression leads to development of cancer.
The lack of good animal models to study how these viruses cause disease has prevented research and development of vaccines and antiviral therapies. Our humanized mice support infection with each of these viral pathogens. Further, human immune responses can be detected against the pathogens, making this a promising model to study vaccines. Work in our lab involves infecting humanized mice with various viral pathogens, and then studying how disease is caused. Immunization strategies are being investigated to develop potential vaccines for humans. Additionally, antiviral drugs can be tested for efficacy and toxicity. Those who work in the lab gain valuable experience in the areas of: laboratory mouse handling/manipulation, mouse injections, mouse dissections, drawing blood, production of virus stocks, virus titering, tissue culture, handling infectious substances, RNA in situ hybridization, immunostaining, flow cytometry (FACS), DNA and RNA extraction, PCR, RT-PCR, and Quantitative PCR, ELISA, and analysis of human immune responses (antibody and cellular).
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