What!!!!!!Human interferons emerges ??

Resistance to Human Interferons Emerges in SARS-CoV-2 Variants

SARS-CoV-2 is the virus that causes COVID-19. Since we first encountered it in late 2019, the virus has continued to mutate into new variants and subvariants. When a person is infected with SARS-CoV-2, antiviral molecules called interferons can spring into action. Researchers have now found that SARS-CoV-2 is adapting to human interferons, which are one type of inflammatory cytokine. The findings have been reported in the Proceedings of the National Academy of Sciences (PNAS).

Colorized scanning electron micrograph of a cell infected with a variant strain of SARS-CoV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Interferons can perform a variety of functions, including attracting other immune cells to the site of infection, activating a massive antiviral response. Interferons themselves can also disrupt the replication of viruses. Many viruses that infect humans are known to have developed some type of resistance to interferons, such as human cytomegalovirus (HCMV) and the H5N1 influenza virus.

When people are exposed to a pathogen, they build adaptive immunity, and typically generate antibodies that help them trigger a more robust immune response if the pathogen is encountered again. Naturally, there has been a lot of focus on whether SARS-CoV-2 can evade antibodies, because if so, people are more likely to continue to get sick if they are exposed again. But there are other changes in the virus as well.

"SARS-CoV-2 just recently crossed the species barrier into humans and continues to adapt to its new host," said study co-author Eric Poeschla, MD, a professor at the University of Colorado School of Medicine. "Much attention has deservedly focused on the virus's serial evasions of neutralizing antibodies. The virus seems to be adapting to evade innate responses as well."

In this study, the researchers analyzed what happened when SARS-CoV-2 interacted with various interferons.

"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. For example, substantially more interferon would be needed to inhibit the Omicron variant than the strains isolated during the earliest days of the pandemic," explained study co-author Mario Santiago, Ph.D., an associate professor at the University of Colorado School of Medicine.

Clinical trials that are evaluating the impact of interferons on COVID-19 may need to be reassessed according to which variant was infecting people at the time of the trial, noted the researchers. It may also be important to determine which viral protein is countering the effect of interferons.

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