This research will explore whether responses to Hepatitis C virus ("HepC") infection by a specific type of immune T cell, called "CD8 T" cells, determines whether the virus persists to cause cirrhosis or liver cancer, or whether it is cleared from the body.
Persistent HepC viral infection can cause death from liver failure or cancer. In the US, HepC results from use of contaminated needles passed among people injecting illicit drugs, blood transfusions with infected blood, transplantation of infected organs or tissues, and, rarely, from sexual transmission. HepC occurs in about one-quarter of people with HIV infection and has become a leading cause of death among this population. Moreover, HepC is the major cause of liver cancer in the US, and the incidence of this cancer has doubled in the last 20 years. Since HepC causes liver failure or cancer only if the infection persists, however, it is vital to improve methods for clearing it from the body.
The researchers hypothesize that the quality of anti-HepC responses by immune CD8 T cells determines whether or not HepC persists or is effectively eliminated from the body. They suspect that there are functional differences among CD8 T cells, emanating from genetic and environmental interactions, which render CD8 T cells in some people unable to recognize HepC infection. While the prevailing immunological view of chronic infection is that the virus mutates to escape CD8 T immune cell responses, the investigators are pursing the possibility that a malfunction also occurs in the way CD8 T cells respond to conserved parts of the virus. To test this hypothesis, they will study intravenous drug users with HepC infection. Typically, these individuals do not have symptoms of HepC, and about 78 percent of them develop persistent infection. The investigators will try to identify how the responses of CD8 T cells differ among those who develop persistent infection compared to those who do not.
Significance: This research could lead to methods to improve immunity against HepC virus infection among intravenous drug users, reducing their risk of eventual death from liver failure or the development of liver cancer caused by persistence of this infection.