Researchers from Princeton University in New Jersey have determined that the herpes simplex virus type 1 (HSV-1) only requires one or two individual viral particles to attack the skin cell in the first stage of an outbreak. This “bottleneck” stage of HSV-1 infection could represent a new point of initiation for treatment at a time when the virus is most vulnerable.
The low number of viral particles present during the initial HSV-1 infection put the virus at a lesser chance of survival compared to other viruses, mostly notably HIV, that require a larger number of genomes to survive, according to the researchers, because a greater number of viral particles increase the virus’s likelihood of surviving and spreading. As Lynn Enquist, the Henry L. Hillman Professor in Molecular Biology and the Princeton Neuroscience Institute, explains, “The number of different genomes that infect the cell is remarkably low, so any mutations that weaken the virus are unlikely to survive. Only the most fit viral particles will survive and replicate in the epithelial [skin] cells, and be available to transmit to the next individual.”
While such bottlenecks can ensure that only the most fit viruses are transmitted to the next individual, they may also represent points at which the virus is more susceptible to immune system responses and drug treatments, explains Matthew Taylor, a postdoctoral researcher in Enquist’s lab and first author of the paper on the study that was published in PNAS.
Julie Pfeiffer, an associate professor of microbiology at the University of Texas Southwestern Medical Center, says the Princeton research is the first to tally how many viral particles are involved in HSV-1 infection — and reveal that as the virus' weak point.
"This work changes the way that we think about herpes virus spread," said Pfeiffer, who was not involved in the study. "This study demonstrated that these neuron-to-epithelial cell viral-transmission events are surprisingly efficient, but they are initiated by a very small number of viruses. This work has interesting implications for herpesvirus transmission and evolution."
