How does the immune system regulate chronic viral infections?
Herpesviruses are viruses that establish lifelong chronic infections. During chronic infection, the virus is maintained in a latent state; however, it undergoes brief periods of reactivation. One of the lab's interests is how this balance between latency and reactivation is maintained by the host immune system.
During her postdoctoral work, Dr. Reese showed that the cytokine IL-4 is a regulator of herpesvirus latency. IL-4 signals directly to viral promoters and drives viral reactivation. In contrast, another cytokine, IFN-gamma , through signaling to the same viral promoter, inhibits viral reactivation. These two host cytokines appear to counterbalance each other.
Through the use of parasitic co-infections that induce IL-4 production, Dr. Reese demonstrated that certain types of co-infections could reactivate herpesvirus infection. Her lab studies how host-derived signals that promote viral reactivation, and how bystander infections can modulate these signals.
How does chronic infection change the immune system’s ability to respond to secondary challenges?
The state of the immune system and its ability to respond to challenge is a function of many variables, which include genetics, age, chronic disease, gut microbiome, and stress. Recent work suggests that a significant proportion of the variation in human immune response is driven by non-heritable or environmental influences. Chronic infections with pathogens (including mycobacteria, helminths, malaria parasites, and some types of viruses) affect a large proportion of the population.
In addition to the diseases caused by these pathogens directly, it is increasingly clear that these persistent infections change immunity to other unrelated pathogens and to vaccines. While epidemiological and clinical data demonstrate an association between bystander chronic infections and altered immune responses there is little mechanistic data to explain these associations.
A more detailed understanding of the immune mechanisms could improve vaccine efficacy and treatment of chronic infections. Using chronic viral and helminth infections, we seek to further define the role of co-infections on vaccine responses in the mouse system.