By Holly Giles | Deputy Editor
COVID-19 has dominated every headline and new story of our lives for the past twelve months, but it has also transformed the scientific community with thousands of researchers turning their attention to COVID-19 in order to better understand the virus. One of the many fields affected by COVID-19 is the field of genetics with researchers trying to identify genes involved in infection.
This has now been realised with scientists at Sanford Burnham Prebys identifying a set of human genes that fight the viruses behind COVID-19 infection.
Lead author of the study, and professor and director for the Immunity and Pathogenesis Program at Sanford Burnham Prebys, Dr Sumit K Chanada explained the importance of this research:
“We wanted to gain a better understanding of the cellular response to SARS-CoV-2, including what drives a strong or weak response to infection. We’ve gained new in-sights into how the virus exploits the human cells it invades, but we are still searching for its Achilles heel so that we can develop optimal antivirals”.
It was observed early on in the pandemic that a weak immune response to infection, led to more severe cases of COVID-19 so increased understanding of the factors determining this response will help scientists predict individuals likely to be most affected by the infection.
The immune response centers around interferons which trigger genes, called interferon-stimulated genes (ISGs), which fight infection by producing proteins which prevent certain actions being completed by the virus.
Explaining their research, Chanda told:
“We found that 65 ISGs controlled SARA-CoV-2 infection, including some that inhibited the virus’ ability to enter cells, some that suppressed manufacture of the RNA that is the virus’ lifeblood, and a cluster of genes that inhibited assembly of the virus. What was also of great interest was the fact that some of the ISGs exhibited control across unrelated viruses, such as seasonal flu, West Nile and HIV, which leads to AIDS.”
This was echoed by first author of the study, Dr Laura Martin-Sancho, who told: “We identified eight ISGs that inhibited both SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging, suggesting this vulnerable site could be exploited to clear viral infection. This is important information, but we still need to learn more about the biology of the virus and investigate if genetic variability within these ISGs correlates with COVID-19 severity”.
One of the key genes identified in the study is BST2 which was described in the article as “a potent inhibitor of SARS-CoV-2 replication” where expression of this gene reduced viral replication by 53% and reduced viral release by 74%. This shows the importance of these genes in controlling viral behaviours and in reducing the virus’ ability to replicate in the body.
This finding has been supported by other studies which have shown the importance of interferons through studying people with interferon protein deficiencies (which occur through genetic mutations). They found that 3.5% of individuals with severe COVID-19 studied had these deficiencies, showing the importance of interferons in the immune response to infection.
The research by Chanda and colleagues is far from complete with the researchers planning to next look at the evolving variants of COVID-19 and how the identified ISGs interact with these new mutations. The researchers explained that they have already starting gathering variants for laboratory investigation and plan to start tests soon.
Despite case numbers decreasing due to the roll-out of vaccines, Chanda explains why the research is still relevant and needed:
“It’s vitally important that we don’t take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic. We’ve come so far so fast because of investment in fundamental research at Sanford Burnham Prebys and elsewhere, and our continued efforts will be especially important when, not if, another viral outbreak occurs”.
It is hoped that this research could increase understanding of how the body naturally fights infection and to identify novel drug targets to increase clinicians arsenal of tools in patients needing intervention to fight the infection more efficiently.
This work by Chanda et al marks another step of increased understanding about the virus behind COVID-19 and another advance in our methods to control it.