Leib Lab / Projects

Herpes simplex virus

Herpes simplex virus (HSV) is a common ocular pathogen causing a variety of diseases ranging from self-limiting dendritic epithelial keratitis, conjunctivitis, and blepharitis to necrotizing stromal keratitis. HSV exhibits two different modes of gene expression during its life cycle. During the replicative phase of infection all of its genes are expressed. During latency, however, viral gene expression is almost completely repressed. Our interest is to define the nature of this switch between the replicative and latent phases of infection. A combination of genetics, molecular biology and virology has allowed us to eludicate viral and cellular factors that control viral gene expression during the establishment and reactiviation of latency. Our approach is to manipulate cloned viral genes and then introduce engineered mutations into the viral genome to generate recombinant viruses allowing the study of viral pathogenesis at the molecular level.

A number of viral gene products presently under study are important determinants of viral pathogenesis or alternatively are important for regulating the balance between lytic and latent infection. We are investigating the roles of innate immunity, particularly interferons and interferon-induced factors in modulating acute infections of both mutant and wild-type viruses. We are using knockout mice to investigate whether mutations in host genes can compensate for mutations in viral genes that result in impaired growth in normal mice. Using real-time in vivo imaging following infection of such mice we are also able to visualize the spread of viruses from the ocular surface to surrounding tissues in a non-invasive fashion. We are thereby elucidating the specific interplay between viral and host factors which are pivotal in determining the pathogenesis of viral infections.