The 2001 Garrod lecture. The treatment of cytomegalovirus infection

Abstract

This named lecture provides an opportunity to take an historical perspective on cytomegalovirus (CMV) infection. A major theme will be that modern molecular biological research has questioned the conventional wisdom that CMV is a slow-growing virus, which only damages a few individuals. I will first review details of the genetic constitution of the virus, emphasizing that wild strains contain many genes which are missing from their laboratory-adapted cousins. I will then review the diseases associated with CMV, not just the end-organ diseases of pneumonitis/retinitis, etc., but the so-called indirect effects, including graft rejection, secondary microbial infections and accelerated atherosclerosis. The urgent need for safe and potent antiviral drugs to prevent these diseases will be considered in two ways: first, the failure of the conventional drug discovery approach; and secondly, the opportunities offered by targeting novel gene functions. The controlled clinical trials performed to date will be summarized, together with suggestions about pharmacodynamic evaluations in the future.