For the first time researchers have direct evidence that viruses can infect neuronal cells, raising hope that antiviral therapy might be effective against neurologic diseases such as multiple sclerosis (MS) or Alzheimer's disease, according to a new study.
The data demonstrate that Epstein Barr Virus (EBV) and Kaposi's sarcoma–associated herpesvirus (KSHV) are able to effectively infect neuronal cell lines, as well as primary neurons. “This phenomenon may potentially provide clues to their contribution to the pathogenesis of human neural diseases,” stated the researchers, led by senior author Erle S. Robertson, PhD, of the University of Pennsylvania in Philadelphia, PA.
Increased titers of EBV, a member of the gammaherpes virus family, have been reported in MS patients. EBV is clinically linked to a wide range of neural ailments, such as primary central nervous system (CNS) lymphoma, MS, Alzheimer’s disease, cerebellar ataxia, subacute sensory neuropathy, meningoencephalitis, cranial nerve palsies, and Guillain-Barré syndrome, the researchers noted.
“The association of EBV with these diseases is based largely on the fact that cerebrospinal fluid (CSF) samples from neurologically compromised patients contain unusually high EBV titers. As a result, testing of the CSF of patients evaluated for neurological disease for EBV is becoming more common,” they stated.
EBV can be present in the CNS, in infected B cells or plasma cells, or in the CSF of neurologically affected patients. The researchers questioned whether is it possible that the presence of EBV or KSHV in the brain and periphery may be a result of direct infection of neuronal tissue, more specifically, neurons themselves.
To date, no in vitro study has demonstrated gammaherpes virus infection of neuronal cells. Worldwide clinical findings have linked EBV to neuronal pathologies, including primary central nervous system lymphoma and Alzheimer’s disease, as well as MS, they stated.
“In this study, for the first time, we have successfully demonstrated the in vitro infection of Sh-Sy5y (a human neuroblastoma cell line) and Ntera2 cells (a neuronally committed human teratocarcinoma cell line), as well as human primary neurons. We have also determined that the infection is predominately lytic. Additionally, we also report infection of neuronal cells by KSHV in vitro similar to that by EBV,” stated the authors.
They believe that these findings may “open new avenues of consideration related to neuronal pathologies and infection with these viruses. Furthermore, their contribution to chronic infection linked to neuronal disease will provide new clues to potential new therapies.”
In many debilitating neurodegenerative diseases, including MS, the efficiency of electrochemical signals is greatly reduced, they noted, often leading to problems related to cognition and muscular activity. “It is likely that viral infection with EBV or KSHV may severely reduce these signals, leading to reduced cognition and reduced neuromuscular function,” they stated.
The results clearly show that infection of neuronal cells can occur, but the researchers note this does not prove that viruses cause these diseases.
Further studies are needed to understand the underlying mechanism of these infections and their relevance to neuronal diseases.
Reference: Jha HC, et al. Gammaherpesvirus Infection of Human Neuronal Cells. MBio. 2015 Dec 1;6(6).