Why Are Viral Infections Less Severe In Females Than In Males? The Answer May Lie In An Extra Gene, Study Suggests

Males are generally more susceptible than females to viral infections. The decreased severity of viral infection in females could be due to an extra gene linked to the X chromosome, a new study states

Natural killer cells in human females have an extra copy of an X chromosome-linked gene called Kdm6a. This gene encodes a protein called UTX, which boosts antiviral function of natural killer cells.

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Viral infections are often less severe in females than in males, a mystery that has intrigued scientists for a long time. Since males are generally more susceptible than females to viral infections, these illnesses are often considered to be sex based. 

The decreased severity of viral infection in females could be due to an extra gene linked to the X chromosome, a new study suggests. 

More about the gene which makes females less susceptible to viral infections

The gene is an epigenetic regulator, which refers to a naturally occurring compound in the body operating inside the nucleus of a cell to turn the expression of multiple genes "on" or "off". The epigenetic regulator which is responsible for decreased severity of viral infection in females boosts the activity of specialised antiviral immune cells known as natural killer (NK) cells. 

The study describing the findings was published March 16 in the journal Nature Immunology. Research conducted on mice and humans showed that NK cells in female mice and humans have an extra copy of an X chromosome-linked gene called Kdm6a. This gene encodes a protein called UTX. UTX serves as an epigenetic regulator to boost NK cell antiviral function, and also represses NK cell numbers. Kd6ma is located on the X chromosome. 

In a statement released by University of California, Los Angeles, Dr Maureen Su, co-senior author on the paper, said while it is well-known that males have more NK cells compared to females, researchers did not understand why the increased number of NK cells was not more protective during viral infections. 

Su explained that females have more UTX in their NK cells than males, which allows them to fight viral infections more efficiently. 

Whether or not the mice had gonads, or reproductive organs, the fact that females have decreased viral severity was held true. This indicates that the observed trait was not linked to hormones. 

According to the study, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection. 

Females with Turner syndrome can have UTX deficiency because they are born with a single X chromosome. 

Mandy Cheng, the lead author on the paper, said the study implicates UTX as a critical molecular determinant of sex differences in NK cells. 

The researchers noted that the study findings suggest that therapies involving immune responses must move beyond a "one-size-fits-all" approach and toward a precision medicine model, also known as personalised medicine. A precision medicine model will tailor treatments that take into account people's individual differences, such as genetics, environment and other factors that influence health and disease risk. 

Co-senior author Tim O'Sullivan said there is a need to incorporate sex as a biological factor in treatment decisions and immunotherapy design. 

The researchers noted in the paper that the findings will be beneficial not only in treating viral infections, but also in other infections and cancer, where NK cells also play an important role.