Herpes type 1 or herpes simplex virus type 1 (HSV1) is a disease that hibernates in the peripheral nervous system and can never be eradicated. A new study from Northwestern Medicine has uncovered 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. The study was published in the ‘Nature Journal’.
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 keep herpes from invading the nervous system,” said Greg Smith, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine. The Northwestern Medicine study from Smith’s lab found a way to do this. The study discovered how herpes kidnapped a protein in epithelial cells and turned it into a defector to help it travel through the peripheral nervous system. They called the process “assimilation”. It’s a discovery that may have far-reaching implications for many viruses, including HIV and SARS-CoV-2, Smith said.
“The virus has to inject its genetic code into the nucleus, so that it can start producing more herpes virus,” Smith said. “It reprograms the cell so that it becomes a virus factory. The big question is how does it get to the nucleus of a neuron? Smith added.
Like many viruses, herpes jumped on train tracks in a cell called microtubules and used 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 has become a defector to serve the purpose of the virus. “By learning how the virus achieves this incredible feat to enter our nervous system, we can now think about how to suppress this ability,” Smith said.
“If you could stop it from taking in kinesin, you would have a virus that couldn’t infect the nervous system. And then you have a candidate for a preventative vaccine,” Smith added. 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.
“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 hub,” Smith added.
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 removed epithelial cells from the mucosa and was convinced 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 first author Caitlin Pegg, a graduate student at Smith’s lab.
“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. (ANI)
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