James Whitton, MD, PhD

Viral Pathogenesis and Antiviral Immunity

My lab's research focused on making life as difficult for viruses as they do for us. To this end, we work on: (i) antiviral immunity (how does the infected host control infection, & how do antiviral vaccines work?); and (ii) viral pathogenesis (how do viruses cause disease?). Most immune responses recognize short stretches of microbial protein, and T lymphocytes see peptides of around 9-16 amino acids in length. Our work on regulation of antiviral T cells has shown that these cells initiate and terminate their effector functions within moments of encountering the relevant peptide antigen. Our vaccine studies have shown that these short immunogenic peptides can be linked end to end in a "string of beads", resulting in a vaccine which, in one shot, can confer immunity against several pathogens. We are currently analyzing plasmid DNA vaccines, which work rather well, but whose underlying mechanisms remain unclear. For our studies on pathogenesis we employ coxsackievirus, which is a common cause of myocarditis (heart disease); we are evaluating the role of the immune system in this disease, and have found that we can interrupt certain components of the immune response, to relieve myocarditis without compromising the ability of the host to eradicate the infection.