The passage of herpes through the nervous system is facilitated by a sinister trick.
- Scientists find out how herpes kidnaps proteins to infect the nervous system
- Opens the door to the long-awaited HSV1 and HSV2 vaccines
- More than half of American adults carry HSV1 herpes
- The virus can cause blindness, a life-threatening encephalitis and can contribute to dementia
Type 1 herpes is sealed with a kiss for life. More than half of American adults carry HSV1 (herpes simplex virus type 1) which hibernates in the peripheral nervous system and can never be eradicated.
A new study from Northwestern Medicine published in Nature discovered the virus’s underhand strategy to infect the nervous system, paving the way for the development of much needed vaccines for HSV1 and its close sibling HSV2.
Some carriers will never even experience as much as an HSV1 cold sore. But for others, it can cause blindness or fatal encephalitis. There is a growing body of evidence that it contributes to dementia.
And HSV2, which is more commonly transmitted through sexual contact, can be passed from mother to newborn during the birthing process as neonatal herpes, appearing as lesions all over the infant’s body. Most babies will recover, but in the worst case it can cause brain damage or spread to all organs and be fatal.
“We desperately need a vaccine to prevent herpes from invading the nervous system,” said Gregory Smith, PhD, professor of microbiology-immunology.
The new study from Smith’s lab has found a way to do this. The study discovered how herpes kidnaps a protein in epithelial cells and turns it into a defector to help it travel through the peripheral nervous system. They called the process âassimilationâ. This is a discovery that may have broad implications for many viruses, including HIV and SARS-CoV-2, said Smith.
Ride the rails
âThe virus has to inject its genetic code into the nucleus, so that it can start producing more herpes virus,â Smith said. âIt reprograms the cell so that it becomes a virus factory. The big question is how does it get to the nucleus of a neuron? “
Like many viruses, herpes jumps on train tracks in the cell called microtubules and uses protein motors called dynein and kinesin to move along the tracks. Smith’s team discovered that herpes uses a kinesin motor that it brings from other cells to transport it to the neuron’s nucleus. This kinesin protein becomes a defector to serve the purpose of the virus.
âBy learning how the virus does this incredible feat to get into our nervous system, we can now think about how to suppress this ability,â Smith said. âIf you could keep him from getting kinesin, you would have a virus that couldn’t infect the nervous system. And then you have a candidate for a preventative vaccine.
Herpes makes a trip “across the country”
Imagine the cell as a marshalling yard. All the tracks lead to the hub called the centrosome. There are two types of locomotives: dynein and kinesin proteins. One is heading towards the hub – let’s say downtown – and the other is heading away towards the suburbs.
When a more typical virus, such as influenza, infects mucosal epithelial cells (cells that line the nose and mouth), it clings to both motors and travels back and forth through the microtubular pathways to what ultimately happens to the nucleus more or less by chance. Overall, going from the suburb to the nucleus, via the centrosome, is a short ride.
But traveling on the nerves is the equivalent of a trip across the country. Herpes is hopping on the dynein motor for this trip, but he also makes sure the kinesin motors don’t bring him back as he came.
âIt’s a long way to go,â Smith said. “It probably takes eight hours for it to travel from the end of the neuron to the hub.”
But the dynein motor can’t go any further than the hub. And the herpes has to reach the nucleus. It was then that he put his hand in his “pocket” and took out a kinesin motor that he kidnapped epithelial cells from the mucous membrane and convinced him to be part of his team. And in an act of betrayal, this assimilated kinesin carries it to the nucleus.
“This is the first discovery of a virus reusing a cellular protein and using it to induce subsequent cycles of infection,” said Caitlin Pegg, a student in the Driskill graduate program in life sciences ( DGP) and lead author of the study.
“We are excited to learn more about the molecular mechanisms behind the evolution of these viruses which make them arguably the most potent pathogens known to science,” Smith said.
Reference: âHerpes viruses assimilate kinesin to produce motorized viral particlesâ by Caitlin E. Pegg, Sofia V. Zaichick, Ewa Bomba-Warczak, Vladimir Jovasevic, DongHo Kim, Himanshu Kharkwal, Duncan W. Wilson, Derek Walsh, Patricia J. Sollars, Gary E. Pickard, Jeffrey N. Savas and Gregory A. Smith, November 17, 2021, Nature.
DOI: 10.1038 / s41586-021-04106-w
Other Northwestern contributors to the study are Sofia Zaichick, PhD; and the laboratories of Jeffrey Savas, PhD, assistant professor in the department of neurology Ken and Ruth Davee, division of behavioral neurology; and Derek Walsh, PhD, professor of microbiology-immunology. The labs of Duncan Wilson, PhD (Albert Einstein College of Medicine) and Patricia Sollars, PhD and Gary Pickard, PhD (University of Nebraska-Lincoln) also contributed to the study.
Smith is a fellow of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The research was primarily funded by the National Institutes of Health AI056346, with additional support from AI125244, AI148780, AI141470 and NS106812, the National Science Foundation, and the Cellular and Molecular Basis of Disease Training Grant T32GM08061.