Researchers at the University of Colorado Anschutz Medical Campus have been investigating how antiviral proteins called interferons interferons with SARS-CoV-2 cause COVID-19. The study, published in Proceedings of the National Academy of Sciences, focuses on how the innate arm of the immune system defends itself against this coronavirus. The work is the result of a collaborative effort by multiple scientists, including the labs of Mario Santiago, Ph.D., associate professor of medicine, and Eric Poeschla, MD, professor of medicine, both at the University of Colorado School of Medicine.
While the adaptive arm of the immune system definitively responds to infection by generating antibodies and T cells, the innate arm forms an earlier, first line of defense by recognizing conserved molecular patterns in pathogens. “SARS-CoV-2 has recently crossed the species barrier in humans and continues to adapt to its new host,” Poeschla says. “A lot of attention has rightly been given to the serial evasion of neutralizing antibodies by the virus. The virus also appears to be adapting to evade innate responses.”
Interferons are central molecules in 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 virus levels initially produced by an infected individual.
“They are clinically viable therapeutic agents that have been studied for years for viruses such as HIV-1,” Santiago says. “Here we looked at 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 their antiviral effects. More interferon would be needed. to inhibit the omicron variant than the strains isolated during the early days of the pandemic.”
The data suggests that clinical trials of COVID-19 with interferons — dozens of which are listed on clinicaltrials.gov — may need to be interpreted based on the variants in circulation when the study was conducted. Researchers say future work to decipher which of SARS-CoV-2’s many proteins might evolve to confer interferon resistance may help in that direction.
Could the COVID-causing coronavirus outsmart the human innate immune response?
Kejun Guo et al, Interferon resistance of emerging SARS-CoV-2 variants, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2203760119
Provided by University of Colorado School of Medicine
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