Researchers at the University of Colorado Anschutz Medical Campus have investigated how antiviral proteins called interferons interact with SARS-CoV-2, the cause of COVID-19. The study, published in Proceedings of the National Academy of Sciences USA, focuses on how the innate arm of the immune system defends against this coronavirus. The work was the result of a collaborative effort by several scientists, including the laboratories of Mario Santiago, PhD, associate professor of medicine, and Eric Poeschla, MD, professor of medicine, both at the University’s School of Medicine from Colorado.
While the adaptive arm of the immune system responds definitively to infection by generating antibodies and T cells, the innate arm forms a first line of defense by recognizing conserved molecular patterns in pathogens.
SARS-CoV-2 recently crossed the species barrier in humans and continues to adapt to its new host. Much attention has deservedly been focused on the serial evasions of virus-neutralizing antibodies. The virus appears to be adapting to evade innate responses as well.”
Eric Poeschla, MD, professor of medicine at the University of Colorado School of Medicine
Interferons are central molecules of the innate immune system that trigger a cascade of antiviral responses in cells within minutes of infection. As such, the interferon pathway could significantly reduce the levels of virus initially produced by an infected person.
“These are clinically viable therapeutic agents that have been studied for years for viruses like HIV-1,” says Santiago. “Here we analyzed up to 17 different human interferons and found that some interferons, such as IFNalpha8, more strongly inhibited SARS-CoV-2. Importantly, later variants of the virus have developed significant resistance to its antiviral effects. For example, substantially more interferon would be required to inhibit the omicron variant than the strains isolated during the first days of the pandemic.”
The data suggest that the COVID-19 clinical trials of interferons, dozens of which are listed at clinicaltrials.gov, may need to be interpreted based on which variants were circulating when the study was conducted. The researchers say that future work to decipher which of the multitude of SARS-CoV-2 proteins might be evolving to confer resistance to interferon may contribute in this direction.
Source:
University of Colorado Anschutz Medical Campus
Journal reference:
Guo, K. et al. (2022) Interferon resistance of emerging SARS-CoV-2 variants. PNAS. doi.org/10.1073/pnas.2203760119.