Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), can infect and replicate in both cultured and primary neurons, according to a study published in mBio.
Though by no means proving causality, those data do suggest viral infection could underlie at least some of the symptoms of those brain disorders, as well as the potential utility of antiviral drugs as a novel therapeutic strategy, according to Erle S. Robertson, PhD and colleagues from the University of Pennsylvania.
According to Dr Robertson, several lines of evidence suggested the possibility that gammaherpesviruses could infect brain tissue. First, the viruses are enriched in the cerebrospinal fluid and brain tissue of individuals with such conditions as multiple sclerosis (MS) and Alzheimer’s disease. In addition, people with a history of infectious mononucleosis caused by EBV are more likely to develop MS, while those who have never been infected with EBV are less likely to do so. Particularly tellingly, the drug acyclovir, which can inhibit EBV and related viruses, has been examined as a potential treatment for MS, with some positive, albeit inconclusive, results.
Using genetically modified viruses that express green fluorescent protein (GFP), the researchers infected human neuroblastoma cells and primary human fetal neurons, monitoring the infection over time by microscopy and protein expression.
In both cell types, infection with either EBV or KSHV resulted in the appearance of a fluorescent signal in the infected cells, as well as the appearance of key viral proteins. The media in which infected cells were grown also contained functional virus particles capable of infecting other cells, indicating a mode of infection that tears open host cells. On the other hand, treatment of infected cells with acyclovir reduced the production of virus particles.
According to Dr Robertson, these data suggest that viral infection of neurons could be associated with neuropathology, though he emphasizes that it is not the same as establishing causality. Such proof, if it ever comes, could be years away.
1. Jha HM, Mehta D, Lu J, et al. Gammaherpesvirus infection of human neuronal cells. mBio. 2015;6no. 6 e01844-15.