Research coauthored by Laure Case, Ph.D., a postdoctoral fellow in the lab of University of Vermont Professor of Medicine and Pathology Cory Teuscher, Ph.D., and published in the October 14, 2011 issue of Science, sheds new light on the mechanisms that allow an HIV-like retrovirus to avoid the immune system and survive. In addition, this new information has provided valuable insight into autoimmune disease research taking place at UVM.

In their Science study, Case and University of Chicago colleagues, including lead author Tatyana Golovkina, Ph.D., focused on an immune evasion strategy used by a retrovirus – mouse mammary tumor virus or MMTV – that suppresses the body’s innate immune system. In the mouse model the researchers examined, MMTV was transmitted through the ingestion of milk by nursing mice born from infected mothers. The group discovered that MMTV exploits the natural bacteria in the host’s gut to induce a state of immune tolerance by turning it into a type of Harry Potter invisibility cloak – it coats itself with molecules from the gut bacteria, which activates an immune suppression pathway that shuts off the body’s immune system’s antiviral response. This allows the virus to persist in the infected host.

“Like MMTV, human immunodeficiency virus (HIV) is a retrovirus that can be transmitted through mucosal surfaces and these studies may aid in the development of new approaches in the prevention of HIV transmission and the design of therapies,” says Case.

The study also provides insight into processes affecting autoimmune disease prevention. In autoimmune diseases such as multiple sclerosis (MS), lupus and rheumatoid arthritis, the immune system mistakenly attacks and destroys healthy body tissue. According to Case, while the induction of immune tolerance is an unwanted occurrence during retroviral infection, a state of immune tolerance toward self antigens is critical for the prevention of autoimmune disease.

Working in Teuscher’s lab at UVM, Case and colleagues are using approaches similar to those used to study retrovirus-host interactions to explore the cellular, molecular, and genetic aspects of susceptibility and resistance to autoimmune disease. The group has found that genetic differences in the Y chromosome can influence the severity of experimental allergic encephalomyelitis, the autoimmune model of MS, in mice. In addition, through a collaborative effort with Sally Huber, Ph.D., professor of pathology at UVM, the investigators have established that the genetic differences in the Y chromosome can also impact the susceptibility of male mice to autoimmune inflammatory heart disease induced by infection with coxsackievirus.

“We believe the Y chromosome has the ability to regulate the expression of genes that reside on other chromosomes in the immune cells and target organs that influence disease,” explains Case. “Investigating the impact of this altered gene expression is critical to enhancing our understanding of the development and progression of MS and heart disease in males and may provide new male-specific targets for therapeutic intervention, as well as improving and personalizing existing therapies,” says Case.