A sinister trick helps herpes examine the nervous system for life

The central nervous system

A sinister trick helps transmit herpes to the nervous system.

  • Scientists discover how herpes hijacks a protein to infect the nervous system
  • Opens the door to the long-requested HSV1 and HSV2 vaccine
  • More than half of adults in the United States carry HSV1
  • The virus can cause blindness and life-threatening encephalitis and may contribute to dementia

Type 1 herpes is sealed with a kiss for life. More than half of adults in the United States are carriers of the herpes simplex virus 1 (HSV type 1), which hibernates in the peripheral nervous system and can never be eradicated.

A new study was published in Northwestern Medicine in temper nature He unveiled the virus’ deceptive strategy for infecting the nervous system, and opened the way for the development of a long-needed vaccine for both HSV1 and its close brother, HSV2.

Some carriers will never suffer like a cold sore from HSV1. But for others, it can cause blindness or life-threatening encephalitis. There is mounting evidence that it contributes to dementia.

And HSV2, which is more commonly transmitted through sexual contact, can be passed from the mother to the newborn during the birth process as neonatal herpes, which appears as lesions all over the infant’s body. Most children recover, but in the worst cases, it can cause brain damage or spread to all organs and be fatal.

“We urgently need a vaccine to prevent herpes from invading the nervous system,” said Gregory Smith, PhD, professor of microbiology and immunology.

The new study from Smith’s lab revealed by way of it. The study discovered how herpes hijacks a protein from epithelial cells and turns it into a splinter to help it travel to the peripheral nervous system. They called the process “assimilation.” It’s a discovery that could have widespread ramifications for many viruses, including HIV and SARS-CoV-2Smith said.

riding rails

“The virus needs to inject its genetic code into the nucleus, so it can start making more herpes viruses,” Smith said. It reprograms the cell to become a virus factory. The big question is how do you get to the nucleus of a neuron? “

Like many viruses, herpes jumps on train tracks in a cell called microtubules and uses protein motors called dynein and kinesin to move along the tracks. Smith’s team discovered that herpes uses a motor of kinesin it brings with it from other cells to transport it to the neuron’s nucleus. The kinesin protein becomes deficient to serve the purpose of the virus.

“By figuring out how the virus achieves this amazing feat of getting into our nervous system, we can now think about how to undo this ability,” Smith said. If you can prevent it from ingesting kinesin, you will get a virus that cannot infect the nervous system. And then you have a preventive vaccine candidate.”

Herpes takes a trip across the country

Imagine the cell as a railway yard. All paths lead to the axis called the centrosome. There are two types of train drives: dynein and kinesin proteins. One travels toward the axis – say downtown – and the other leads you away from it into the suburbs.

When a more common virus, such as influenza, infects mucosal epithelial cells (the cells that line your nose and mouth), it grabs on both motors and moves back and forth on microtubule pathways until it eventually reaches the nucleus more or less by accident. In general, the transition from the outskirts to the nucleus, via the centrosome, is a short journey.

But traveling down the nerves is equivalent to a cross-country trip. Herpes jumps on the dynein drive on this trip, but he also makes sure the kinesin drives don’t take it back as it came.

“It’s a long way to go,” Smith said. “It probably takes eight hours for it to travel from the end of the neuron to the axon.”

But the Dynein motor couldn’t take it further than the axle. And herpes needs to reach the nucleus. That’s when he gets into his “pocket” and pulls out a kinesin motor that’s snatched him from the mucosal epithelial cells and is convinced to become part of his team. And in an act of treason, this ingested kinesin transports it directly to the nucleus.

“This is the first discovery of any virus that recycles a cellular protein and uses it to drive later rounds of infection,” said Caitlin Page, a student in Driskill’s graduate program in life sciences and lead author of the study.

“We are excited to reveal the molecular mechanisms developed by these viruses that make them the most successful pathogens known to science,” Smith said.

Reference: “Herpes viruses ingest kinesin to produce automated viral particles” By Caitlin E. Page, Sophia F. Zechik, Ewa Bomba-Warczak, Vladimir Jovacevich, Dong Ho Kim, Himanshu Kharkwal, Duncan W. Wilson, Derek Walsh, Patricia J. Solaris, Gary E. Picard, Jeffrey N. Savas and Gregory A. Smith, 17 November 2021, Available here. temper nature.
DOI: 10.1038 / s41586-021-04106-w

Other Northwestern contributors to the study are Sofia Zayczyk, Ph.D.; the Laboratories of Jeffrey Savas, Ph.D., assistant professor in the Kane and Ruth Dave Department of Neurology, Department of Behavioral Neuroscience; and Derek Walsh, Ph.D., professor of microbiology and immunology. The laboratories of Duncan Wilson (Albert Einstein College of Medicine), Patricia Solares, Ph.D., and Gary Pickard (University of Nebraska-Lincoln) also contributed to the study.

Smith is a member of the Robert H. Lowery Comprehensive Cancer Center in Northwestern University.

The research was funded primarily by National Institutes of Health AI056346, with additional support from AI125244, AI148780, AI141470, NS106812, the National Science Foundation, and the Cellular and Molecular Basis of Disease Training Grant T32GM08061.

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