Work smarter, not harder: cytomegalovirus regulates multiple pathways by impairing one protease

What is it about?

This paper describes a unique viral strategy that human cytomegalovirus (HCMV) uses to evade innate responses of the host. HCMV impairs the function of just one host protease ADAM17, which in turn has an effect on over 100 host and viral proteins, all of which rely on ADAM17-mediated shedding. By targeting a single protease, HCMV is able to manipulate multiple immune pathways to its advantage and evade host immune responses. ADAM17 impairment is mediated by two viral genes UL148 and UL148D that work synergistically to disrupt ADAM17 maturation and, as a result, its ability to perform its shedding function.

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Photo by CDC on Unsplash

Photo by CDC on Unsplash

Why is it important?

HCMV infection can be fatal to immuno-compromised, -deficient or -naïve individuals. HCMV infection in utero results in lifelong disabilities, whilst HCMV reactivation is a huge problem in transplant patients. Current treatment options against HCMV infection are very limited. It is essential to understand HCMV biology in order to develop better treatments against it. Furthermore, protease ADAM17 targeted by HCMV has been implicated in many diseases, such as cancer, chronic inflammatory diseases and diabetes. Understanding how the virus impairs ADAM17 regulation may provide valuable information on general ADAM17 biology and regulation, which would be essential in order to target ADAM17 function for therapeutic purposes,.

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