Abstract presented at the 2017 ACTRIMS conference, February 23-25, in Orlando, FL:
S4.2 Evidence Linking HHV-6 with MS
Dr. Steve Jacobson - NIH-Viral Immunology Section, NINDS
Learning Objectives:
~To understand the role of viruses in the pathogenesis of multiple sclerosis
~ How to make an association of ubiquitous viruses with chronic neurologic diseases
~ Evidence linking human herpes viruses with particular emphasis on HHV6 and multiple sclerosis.
Abstract:
Human Herpes Virus 6 (HHV-6) is a member of the Roseolovirus genus of the β-herpesvirus subfamily. Primary infection is often associated with febrile illness, and is the etiologic agent of the childhood illness roseola infantum. The virus has a worldwide distribution, with an estimated seroprevalence of 95% in the adult population. HHV-6 cell tropism is notably lymphotropic and
neurotropic, and can infect a wide range of human cells in vitro due to the ubiquity of its major receptor, CD46. Similar to other herpesviruses, HHV-6 can establish lifelong latent, asymptomatic infections. However, the virus may reactivate as a febrile illness or encephalitis following bone marrow or solid organ transplantation.
HHV-6 DNA is reported in normal brain tissues suggesting that this virus
may be a commensal of the brain. However, HHV-6 is also associated with neurologic conditions including encephalitis, temporal lobe epilepsy and multiple sclerosis (MS), [associations] which have been established by assessing both the distribution of viral DNA and serologic responses.
HHV-6 DNA is found with increased frequency in MS lesions. HHV-6 DNA has been detected in cell-free compartments, such as sera and urine, of MS patients, and is detected at higher frequencies during periods of clinical exacerbation relative to periods of remission. Despite the association of HHV-6 with several CNS
disorders it has been difficult to prove causation. This is partly due to the ubiquity of HHV-6 infection in the general population.
Animal models of HHV-6 infection have been difficult to establish because
rodents lack the complement regulatory receptor, CD46, that HHV-6 uses for cellular entry. The common marmoset (Callithrix jacchus) is a New World non-human primate that naturally expresses CD46 and is therefore susceptible to infection with HHV-6.
A major focus of our research is to characterize the extent and distribution of ubiquitous herpesviruses in the pathogenesis of MS. We
hypothesize that there may be multiple ‘triggers’ by which foreign antigens, including infectious agents, may be associated with immune attacks on the CNS. We propose that HHV-6 may be one such trigger and if so, the mechanism(s) by which this virus is associated with the pathogenesis of MS will be
important to define. We emphasize that only through well-controlled interventional clinical trials with effective and safe antivirals can a causal role be made for any infectious agent in MS.