Anne A Gershon, MD

Dr. Gerson's research has included epidemiology, diagnosis, immunology, latency, prevention, and treatment of varicella and zoster. Her studies with varicella vaccine which examined the safety and efficacy of the vaccine in leukemic children and adults were critical to its licensure; the vaccine is now recommended for all healthy varicella susceptible individuals in the United States. She is continuing to study the safety and efficacy of varicella vaccine in the “vaccine era”. She has also focused on HIV infection in children, particularly with regard to opportunistic infections. She has received research funding from NIH to study the growth and pathogenesis of VZV in cell culture, and latency and reactivation of VZV in humans and animal models almost continuously for over 40 years.

Basic studies on VZV, in conjunction with Dr. Michael Gershon in Cell Biology (at Columbia) included identification of the mannose-6-phosphate (MPR), a major receptor for VZV, the mechanism of assembly of VZV in cells, and identification of two different types of spread of VZV, from one cell to another and the other by release of cell free VZV in cells of the superficial epidermis, one of the few cells in the body where MPRs are not present. The release of cell free VZV in the superficial epidermis accounts for spread of virus from one individual to another. It also accounts for development of latent infection in patients with varicella. More recently, she and her co-workers have investigated latent infection with VZV in humans (autopsy and surgical specimens) and in an in vitro model of latency and reactivation of VZV utilizing enteric neurons of the guinea pig. Enteric ganglia can be dissected from guinea pigs, cultivated in vitro, and infected with cell free VZV with survival for weeks. The neurons in these cultures manifest VZV infection, which have the latency signature of the virus: expression of genes 4, 21, 29, 62, 63, and 66; transcripts and proteins of these regulatory genes are found only in the cell cytoplasm. This signature matches the one also demonstrated in surgical specimens from human gut that contained enteric neurons in which VZV was found to be latent. In vitro upon introduction of VZV gene 61 to a latently infected guinea pig enteric neuron, the virus reactivates to express all 70 of its genes, and the neuron dies. This unique experimental demonstration of latent infection in intestinal ganglia of guinea pigs was what led to the exploration of whether VZV could be latent in the human gut, leading to conditions such as gastric and intestinal ulcers and pseudoobstruction if reactivation of virus occurs in the enteric nervous system.