Virus World

For a long time, it has been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery – until possibly now. The answer may lie in an epigenetic regulator that enhances the function of specific anti-viral immune cells, referred to as natural killer (NK) cells. A research team from UCLA has recently published a study in the peer-reviewed journal Nature Immunology. The study revealed that female mice and humans possess an additional copy of a gene called UTX, which is linked to the X chromosome. UTX functions as an epigenetic regulator that enhances the anti-viral function of NK cells while suppressing their numbers. “While it is well-known that males have more NK cells compared to females, we did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently,” said co-senior author Dr. Maureen Su, professor of microbiology immunology and molecular genetics, and of pediatrics, at the David Geffen School of Medicine at UCLA.

The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection. “This implicates UTX as a critical molecular determinant of sex differences in NK cells,” said the study’s lead author Mandy Cheng, graduate student in molecular biology at UCLA. “While it is well-known that males have more NK cells compared to females, we did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently,” said co-senior author Dr. Maureen Su, professor of microbiology immunology and molecular genetics, and of pediatrics, at the David Geffen School of Medicine at UCLA. The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection. “This implicates UTX as a critical molecular determinant of sex differences in NK cells,” said the study’s lead author Mandy Cheng, graduate student in molecular biology at UCLA.

Research Cited Published in Nature Immunology (March 16, 2023):

https://doi.org/10.1038/s41590-023-01463-8 

Gut microbes produce compounds that prime immune cells to destroy harmful viruses in the brain and nervous system. The findings suggest that having healthy and diverse microbiota is essential for quickly clearing viruses in the nervous system to prevent paralysis and other risks associated with diseases such as multiple sclerosis. 

"We wanted to investigate whether gut microbes could alter the immune response to a virus in the central nervous system and whether this affects the amount of damage the virus causes," says one of the lead authors David Garrett Brown, a graduate research assistant in the Department of Pathology at University of Utah Health, Salt Lake City, US.

To do this, Garrett Brown and co-lead author Ray Soto looked at the effect of Mouse Hepatitis Virus, a virus that infects cells in the mouse nervous system and causes multiple-sclerosis type symptoms, on two groups of mice: some with normal gut microbes and some that were bacteria-free. They found that bacteria-free mice had a weak immune response, were unable to eliminate the virus and developed worsening paralysis, while those with normal gut bacteria were better able to fight off the virus. Mice treated with antibiotics before the onset of disease were unable to defend themselves. They also had fewer immune cells called microglia, which help flag viruses for destruction by other immune cells.

The studies were published today in eLife:

 https://doi.org/10.7554/eLife.47117