A university study could explain why females may suffer worse outcomes of virus infection such as Covid-19. Researchers from the University of Dundee’s School of Life Sciences found the control of genes on X chromosomes in females can cause much wider effects on cells than previously realised.
The X chromosome – of which females have two and men have only one – contains more than 1,000 genes that are vital for cell development. However, a double dose of such gene products can be lethal, meaning one of the two chromosomes in female cells shuts down in a process known as X chromosome inactivation (XCI).
The team found that issues with the XCI process in female cells can cause major changes in protein levels. Proteins are the main targets of almost every drug and differences in the levels of a cell are frequently responsible for many different types of disease, including cancer.
Alejandro Brenes, an analytics developer at the university school, said: “This study has revealed major consequences for the female cells if the XCI mechanism is defective. “By analyzing a collection of human stem cells from both healthy male and female donors, we found that a defective XCI increased the levels of thousands of proteins from all chromosomes, many of which are known markers of disease.
“The data can help to explain why some people may be more likely to develop specific types of disease, suffer worse outcomes of virus infection, such as Covid-19, or vary in how they respond to treatments and therapy. “The results could also be important for the safe development of stem cell therapies.
COVID-19, has been said to affect men and women differently, with men thought to be more likely to become severely ill and die from the disease.To find out more about sex differences in COVID-19, we spoke to Professor Sabra Klein, from the Johns Hopkins Bloomberg School of Public Health.
According to data from around the world, including preliminary data from the UK, an equal number of males and females contract the disease, but do we see the same symptoms?Where we are seeing real differences, in terms of larger magnitude of a male-female difference is in severity of disease.
When the virus enters our body, it needs to enter our cells in order to replicate. Successfully making it into the cell, the virus tries to replicate itself. Estrogen in women is thought to make this harder, meaning that the virus can’t make as many copies of itself in women.
Once the immune system realizes the virus has infiltrated its cells, it launches an attack to try and clear out the infection from its cells.
Generally speaking, women tend to mount more robust immune responses that can be beneficial for initially recognizing and initiating the clearance of a virus. So that can be beneficial. Where it can be detrimental is if long-term responses are not properly regulated, so you can get excessive immune responses that can contribute to long-term inflammation and that in and of itself can cause some tissue damage.
In addition to these sex differences in physiology, there are also important behavioral differences. Men are less likely to go to hospital until later in their disease. However, as healthcare workers are often women, we may still see a shift away from the male bias of the disease as the pandemic progresses.
“It also highlights the importance of sex-specific studies, as there are still many uncharacterized differences between females and males that need to be better understood in order to advance precision medicine.” The study, Erosion of human X chromosome inactivation causes major remodeling of the iPSC proteome, is published in Cell Reports and can be found online.