Herpes viruses appear to be a little more low-key than the SARS-CoV-2 that is currently wreaking havoc around the globe, as well as more recognizable viruses like HIV and hepatitis B. Their activity, on the other hand, is anything but low-key, and they are possibly the most “successful” infections ever discovered.
Herpes viruses are DNA viruses that cause human disease. There are eight species in the family, with herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) being the typical representatives.
Humans are a natural host for the herpes simplex virus which is extremely common in the population. Only a small percentage of early infections are overt, with mucosal or localized skin herpes being the most prevalent clinical signs. After the first infection, the infection often becomes latent, and external stimulus might trigger recurrence.
HSV-1 is latent in approximately 70% of the world's population, according to the World Health Organization.
The herpes virus remains latent in the host's peripheral nerve system for the rest of their life and can never be eradicated.
Therefore, there is an urgent need to gain insights into how herpes viruses invade the nervous system to enable the development of prevention strategies.
On November 17, in a new study published in Nature, a team of researchers led by Northwestern University has discovered a cunning strategy for herpesvirus infection of the nervous system, further revealing the molecular mechanisms evolved by the virus and opening the way for the development of vaccines against HSV-1 and HSV-2. At the same time, this discovery may have broad implications for many viruses, including SARS-CoV-2 and HIV.
In this new study, a team led by Greg Smith, a professor of microbiology and immunology at Northwestern University Feinberg School of Medicine, discovered how the herpes virus hijacks a protein from epithelial cells and “instigate” that protein to help it enter the peripheral nervous system. They call this process “assimilation”.
Like many viruses, herpesviruses use microtubules to reach the nucleus of neurons, which are fibrous structures in cells that connect different regions and are responsible for maintaining cellular morphology and transporting substances. Herpesviruses jump on the tracks of microtubules and use kinesin as their engines to move along the microtubules.
Traveling along the nerve is the same as traveling cross-country. During this journey, the herpes virus joins the “power train” (power protein engine) and ensures that the protein engine does not carry it back to the “country of departure”. According to researchers, the journey from the end of a neuron to its center can take up to eight hours.
The herpesvirus took out the kinesin engine it had hijacked from the mucosal epithelium and “assimilated” it to become part of its team. In this act of betrayal, this assimilated kinesin transported the herpesvirus directly to the nucleus.
Notably, the kinesin used by HSV-1 is not neuronal endogenous, but is derived from previously infected epithelial cells (from which viral particles are produced).
Overall, viral particles capturing and transporting kinesin between cells enhances the possibility of HSV-1 reusing the captured kinesin to infect cells, including neurons.
“By understanding how the virus achieves this incredible manipulation, we can now consider how to take away their ability to invade the nervous system,” Smith said. “If we can stop it from assimilating the kinesin, we will have a virus that cannot infect the nervous system. Then, the development of a preventive vaccine will become possible.”
He added, “This is the first time that a virus has been found to repurpose a cellular protein and then use them to drive subsequent infectious behavior. We are excited to further discover the molecular mechanisms that have evolved in these viruses, making them arguably the most successful pathogens known to science.”
