Penn State Research: Herpes Virus Can Infect Human Neuronal Cells

Penn State Research: Herpes Virus Can Infect Human Neuronal Cells

By Siwei Zhang

The Epstein-Barr Virus (EBV) is one of a few highly ubiquitous herpes viruses that infects an estimated 90% – 95% of the adult population without noticeable symptoms, regardless of demographics or locations. As a large double-stranded DNA virus, EBV belongs to the human gammaherpesvirus group (human herpesvirus 4). Though this virus mainly infects primary B lymphocytes, it also demonstrates the ability to infect other lymphocytes and a certain type of epithelial cells. Transmission of the virus is through the exchange of body fluids, such as saliva and genital secretions.

In addition of acting as the main cause of infectious mononucleosis, the virus has also been suggested to be associated with several types of human cancers such as Burkitt’s lymphoma and nasopharyngeal carcinoma. Intriguingly, amid a lack of a mechanistic link, the unusual high titre of EBV in cerebrospinal fluid (CSF) has been clinically linked to a wide range of neural diseases including multiple sclerosis (MS), Alzheimer’s disease and cerebellar ataxia. However, whilst the clinical link between high EBV titre and neural diseases such as MS and Alzheimer’s remain strong, the nature of such link remains highly elusive, as the traditional view on the EBV infection mechanism suggests that EBV cannot infect neurons, largely due to the lack of appropriate surface receptors as well as the quiescent nature of differentiated neurons.

However, a recent research published by Jha et al. on mBio suggests otherwise and provides the potential link underlying the high EBV titre in CSF and neural ailments. From their results, they suggest that both undifferentiated and differentiated neuronal cell lines, as well as primary fetal neurons, can be infected by EBV and, moreover, these infected neurons are able to enter the lytic cycle and produce large amount of mature, infectious virus particles. Importantly, acyclovir (ACV), an antiviral drug that has demonstrated ability in EBV treatment as well as alleviation of MS exacerbations, significantly inhibits the genome replication of EBV in human neural cell lines. It is also interesting to note that no apparent latent reproductive stage was observed, as all infected cells soon entered the lytic reproductive cycle and eventually underwent cell lysis within approximately 9 days as the result of virus progeny generation.

Such results imply that the high EBV titre within CSF may not only be an indicator of neural ailment, but may also directly contribute to the damaging effects against neurons in these patients. Further investigations using neuropathological analyses will help further in solving the remaining obscurity presented in this research.


Image Description and Credits:
Image shows primary neuron at day 5 infection with the Epstein-Barr virus (green).
Credit: Hem Chandra Jha, PhD, Perelman School of Medicine, University of Pennsylvania


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