How does SARS-CoV-2 'hide from' the immune system and how can this be tackled?
Theme Lead: Professor Paul Lehner, Professor of Immunology and Medicine at the University of Cambridge
While the human body has many ways to fight infection, viruses are also able to hide from the immune system. This allows the virus to replicate more efficiently and spread faster, leading to worse disease outcomes. Researchers are starting to understand that SARS-CoV-2 evades immune detection. What they don’t yet understand is the specific ways in which this occurs. Understanding this could help to identify effective new treatments.
There are three outstanding issues that the researchers hope to address through this project:
1. Understanding how SARS-CoV-2 manipulates its host cell to make copies of itself
Based on previous work on other viruses (like HIV), this part of the research will identify weak points in the virus and expose new drug targets. The researchers aim to understand how the virus uses the infected cell to make more copies of itself and to avoid detection. The results will help us understand how SARS-CoV-2 causes disease, as well as find vulnerabilities in the virus that can be exploited when designing new tests and treatments.
2. How the virus evades the innate immune response, including the role of a signalling protein called interferon
When the immune system is functioning normally, and able to detect a new infection, a group of chemicals called interferons play a critical role. These are made and released by a cell when it becomes infected with a virus, in order to protect itself, alert its neighbouring cells, and raise the alarm to cells of the immune system that there is a problem. Interferons play an important part in the early immune response, when it is important to eliminate a virus before it spreads. However, SARS-CoV-2 inhibits interferon production, meaning the immune system is slower to notice the virus and therefore slower to fight back.
The researchers want to understand how this happens, including the role of specific viral genes that allow SARS-CoV-2 to evade the immune system. They also plan to create a list of human gene variants (related to interferon) that can inhibit the virus and see if these are linked to the severity of COVID-19 in patients.
3. How the virus evades the adaptive immune response
There is growing evidence that SARS-CoV-2 also evades the adaptive immune response, which is the more targeted arm of the immune system. About 5 – 7 days after infection, the infected person produces virus-specific antibodies and mobilises other immune cells such as specific killer T cells and natural killer (NK) cells.
These cells help to make antibodies and other protective antiviral responses. Understanding how the virus gets around these cells will be incredibly important. In future, understanding these complex responses may allow us to predict the severity of COVID-19 disease, based on their genetic makeup. It will also aid in vaccine development.
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