September 26, 2021
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Study reveals possible direct link between neurodegenerative diseases and herpes virus

By on September 14, 2021 0

A new study by researchers at the University of Illinois at Chicago suggests that when the optineurin protein, or OPTN, is present in cells, it limits the spread of HSV-1, the herpes simplex virus of type 1.

In a “first of its kind” study, researchers also discovered a potential direct link between neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), glaucoma and the herpes virus, a said Dr Deepak Shukla, of Marion H. Schenk. Esq. Professor of ophthalmology for research on the aging eye and vice-president of research at UIC.

The research paper, “OPTN is an intrinsic host restriction factor against neuroinvasive HSV-1 infection”, led by Shukla, was recently published in the journal Natural communications.

Researchers set out to find out why HSV-1 can be fatal for people with compromised immune systems, but not for healthy people. Herpes viruses naturally infect the central nervous system and can lead to degenerative disorders of the brain and eyes, as well as encephalitis. However, in most people, the virus is suppressed during a primary infection before it can significantly damage the central nervous system.

New research suggests why HSV-1 is deleted: OPTN, a conserved autophagy receptor, selectively targets HSV-1 proteins until degradation by autophagy, explained Tejabhiram Yadavalli, co-author of the study and visiting researcher at the Department of Ophthalmology and Visualization at UIC. science.

OPTN stops the growth of the virus and it stops it by autophagy -; engulfing virus particles inside tiny vesicles called autophagosomes. The autophagy that occurs is very selective. It also makes sense for other viruses. “

Dr Deepak Shukla, the Marion H. Schenk Esq. Professor of Ophthalmology for Aging Eye Research

The researchers believe the results of this study will apply to eight different human herpesviruses.

For the study, mice whose OPTN genes were deleted were infected with ocular HSV-1. Growth of the virus was much higher in the brains of animals without OPTN, killing local neurons and ultimately leading to the death of the animal. This shows that there is faster degeneration of neurons when OPTN is not there. Further studies are planned to examine natural mutations in OPTN, such as those reported in patients with glaucoma and ALS, and how they may affect neuronal health and HSV-1 infection, Shukla explained.

“Where you have mutated OPTN plus herpes, you have the recipe for creating disaster in terms of neurodegeneration,” said Shukla.

“The study also shows that there is an alteration in the immune response when there is an OPTN deficiency. OPTN is needed to signal an influx of appropriate immune cells to the site of infection. ‘have not, you have problems “. said Chandrashekhar Patil, also co-author of the study and visiting researcher in the Department of Ophthalmology and Visual Sciences at UIC.

Some of these problems could include neurodegenerative disorders, which the researchers believe further research may show.

“We think we will have data to show that other viruses, such as Epstein-Barr, Kaposi’s sarcoma, varicella zoster, are all going to share this mechanism because they share homologous proteins,” Shukla said.

Because the herpes virus resides in neurons forever, there is speculation that it is linked to neurodegenerative diseases. The immune system needs inflammation to constantly fight the virus, and neurons suffer some degree of damage from this continued immune response, according to Dr. Tibor Valyi-Nagy, professor of pathology, director of neuropathology at the UIC and research collaborator on the study. .

The study also showed that animals without OPTN and infected with HSV-1 after 30 days lost the ability to recognize objects. Shukla said this could indicate that having HSV-1 with an OPTN mutation could accelerate neural damage, which results in cognitive impairment.

“Part of our translational research may be how to correct issues with OPTN so that we don’t have neurodegeneration issues,” Shukla said.

Source:

Journal reference:

Ames, J., et al. (2021) OPTN is an intrinsic host restriction factor against neuroinvasive HSV-1 infection. Natural communications. doi.org/10.1038/s41467-021-25642-z.


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