Grant promotes research collaboration at multiple institutions

Once competitors for the same grants, Penn State College of Medicine researchers have teamed up with colleagues at Jefferson Medical College of Thomas Jefferson University and Fox Chase Cancer Center to study how the immune system controls viral infections. The multi-year, multi-million dollar grant from the National Institute of Allergy and Infectious Disease will feature a strong collaborative effort to focus on ectromelia virus, a mouse virus that causes mousepox (i.e., mouse smallpox) and serves as a research model for human smallpox. Penn State researchers, under the direction of Chris Norbury, associate professor of microbiology and immunology, will investigate the cell types and mechanisms that are involved in controlling virus infection at the site of infection in the skin.

“This is a fantastic opportunity for us,” Norbury said. “I’ve found myself competing against Luis Sigal, head of the Center at Fox Chase Cancer Center, for many years, and we were moving into an area that would have meant we were competing against Dr. Eisenlohr at Jefferson as well. To turn that around and now to be working with these guys is a real step forward, and it’s really fun being in a room with guys who know the field so well -- the ideas really begin to fly fast and furious.”

Researchers have identified a macrophage-like cell type that is normally associated with suppression of an immune response directed against a tumor. A macrophage is a white blood cell, which defends the body from infectious diseases. Researchers have discovered that this cell type, which normally inhibits the immune response against a tumor, protects against virus infection by producing interferons, proteins that assist in the defense of the body. The macrophage-like cells also significantly reduce virus-induced tissue damage.

Penn State researchers will examine which signals trigger these cells to migrate to the site of infection. They will collaborate with Cynthia Leifer at Cornell University in Ithaca, to investigate how the cells interact with the virus particles, including how the particles are moved inside the cell and how the anti-viral immune response is initiated.

“We kind of stumbled into this through the work of an excellent graduate student in my lab, Matt Fischer, but now that we have described the function of this cell type in an acute virus infection, we think we can make some very big strides,” Norbury said. “The results we’re going to get aren’t only going to be relevant for antiviral immunity. I think manipulation of this kind of macrophage is going to be very important in all kinds of pathologies, from virus infection to cancer to diabetes.”

The Penn State College of Medicine's Department of Microbiology and Immunology also will upgrade its departmental microscopy facility to allow its researchers to image the interactions of fluorescent virus particles with immune cells, as well as to image the interaction of various cell types with virus-infected cells within animals. This facility will support all the microscopy within the project, with samples being shipped from Fox Chase and Jefferson University.

The grant will focus on three main projects, one based at each of the partner institutions, yet inextricably linked through collaboration. Researchers from Cornell University also will contribute to these projects.

Other projects associated with this grant are:

-- Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa. -- Laurence Eisenlohr, professor of microbiology and immunology at Jefferson, and his team at the Jefferson Vaccine Center, will analyze the response of CD4+ T cells in mice to ectromelia virus. Vaccinia, the virus that has been used as the vaccine for smallpox, has been studied frequently, but it is not a natural mouse pathogen and preliminary data show fundamental differences between the mouse responses to these two viruses. In examining mouse CD4+ T cell responses to mousepox, the researchers hope to identify general principles of defense against poxviruses that will likely be applicable to many other viral infections as well.

-- Fox Chase Cancer Center, Philadelphia, Pa. -- Luis Sigal and his colleagues at Fox Chase will focus on two aspects of the immune system: the innate and adaptive response. The adaptive immune response encompasses the development of antibodies and cytotoxic (killer) T cells that provide lasting resistance to infection, while the innate immune system serves as the first line of defense to control the virus. In order to better understand how vaccines protect -- and to develop new vaccines -- the Fox Chase researchers will investigate the mechanisms whereby cytotoxic T cells and antibodies develop a lasting memory of infection. The Fox Chase team will also focus on one aspect of the innate response, the production of Type I interferons, molecules that reduce the spread of the virus and prevent disease. The researchers believe these interferons might help in developing therapies for emerging infections.

 

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Last Updated July 22, 2009