David Mock awarded a National MS Society grant to study HHV-6A U94 and remyelination

David Mock, MD of the University of Rochester.

Congratulations to David Mock, MD of the University of Rochester, who has received a pilot grant from the nation’s leading MS non-profit to investigate the role of HHV-6A U94 in impairing the remyelination process. His group plans to develop a novel mouse model in which U94 can be specifically regulated in mouse oligodendrocyte progenitor cells (OPC’s), the cells that typically migrate to the site of myelin damage to jumpstart the repair process.

Mock plans to use Cuprizone demyelinated mice to determine the impact of HHV-6 U94 expression. He will work with long-term collaborators Margot Mayer-Proschel and Christoph Proschel to conduct the experiment, which will be the first study to mimic HHV-6 latency, and the first to model the inhibition of repair as opposed to the demyelinating insult.

In 1999, Mock published a case report on the presence of HHV-6 and JC virus in the demyelinative lesions of 10 patients with the demyelinative disease known as progressive multifocal leukoencephalopathy. Immunohistochemistry showed HHV-6 in the swollen oligodendrocytes but not in adjacent, uninvolved tissues (Mock 1999). He was also co-author with Andrew Goodman, MD of the University of Rochester, on a seminal paper that reported finding HHV-6 genome-containing oligodendrocytes in the lesions of patients with MS, suggesting a role for the virus in the pathogenesis of multiple sclerosis (Goodman 2003).

Mock first became intrigued with the idea that HHV-6 might play a role in MS when he read a paper by Louis Flamand in 1993 showing that HHV-6 could upregulate Epstein Barr virus immediate early Zebra antigen by 10-fold and activate the lytic cycle (Flamand 1993). He was also strongly influenced by the Challoner group’s 1995 paper, which detailed the presence of HHV-6 in the oliogodendrocytes of MS patients but not controls, as well as two papers by Dario Di Luca’s group: a 1998 paper showing low level but long term expression of U94 in human mononuclear cells, and a subsequent paper in PNAS demonstrating that HHV-6 inhibits migration of endothelial cells and blocks angiogenesis (Caruso 2009).

One of Mock’s favorite heroines in medicine is Ruth Itzhaki, PhD, a pioneer in the study of latent HSV-1 in brain tissue and its possible impact on Alzheimer’s disease. He is confident that although it has been underappreciated for decades, she will eventually be remembered for playing a pivotal role in early studies on the impact of latent CNS herpesviruses (Itzhaki 2014).

Although he spends most of his time as an infectious disease physician, Mock is an enthusiastic catalyst for HHV-6 research, relentlessly seeking new collaborators and ideas to move the field further.