Predicting endemic viruses in an evolutionary struggle with the immune system

Among the 28 endemic viruses analyzed in this study, the authors included rapidly evolving influenza and coronavirus strains as well as antigenically stable viruses such as measles and hepatitis A. They ensured that the selected viruses had high-quality genome sequences that spanned at least 12 years to predict accurate adaptation rates. To identify viruses that are undergoing antigenic evolution (adaptive evolution driven by positive selection to evade antibody recognition), Dr. Kistler used a quantitative approach that calculated adaptive amino acid substitutions per residue per year. Since “antigenic evolution occurs through viruses acquiring antibody escape mutations,” it is predicted that these escape mutations will “occur in viral proteins that mediate receptor binding, which are located on the virion surface and are typically the primary target of neutralizing antibodies. “. In other words, Dr. Kistler explained, “We looked for excess protein-coding changes in the proteins that mediate receptor binding.” Dr. Kistler analyzed 239 viral proteins across all viruses, but she said, “We Only 14 are estimated to be adaptively evolving.” Of these, 13 are located on the virion surface and “either are major receptor-binding proteins or are at least sometimes involved in receptor binding,” while the rest of the genome shows little ongoing adaptation. These 14 protein-coding genes belong to 10 of the 28 viruses analyzed in this study, indicating that nearly one-third of the endemic viruses analyzed are expected to undergo antigenic evolution. However, Dr. Kistler acknowledged that the group’s bias toward viruses with sufficient historical sequences may not reflect the overall proportion of endemic viruses that have evolved antigenically. Consistent with our need for annual influenza vaccination, influenza A/H3N2 evolves approximately 2-3 times faster than other viruses analyzed.

“An obvious question is where the evolution of SARS-CoV-2 stands relative to these other viruses,” the authors explain in the paper. They also note the challenges of using the paper’s approach with viruses that have been around for a shorter period of time. challenge. Instead, the authors compared amino acid substitution rates in receptor-binding proteins between SARS-CoV-2 and 10 viruses predicted to undergo antigenic evolution. Dr. Kistler found that SARS-CoV-2 accumulates amino acid substitutions 2-2.5 times faster than the rapidly evolving A/H3N2 influenza. While this may sound concerning, the authors note that we do not know whether SARS-CoV-2 can sustain such a high rate of evolution, nor whether the emergence of highly fitting Omicron variants is a one-time event. There are likely many reasons why viruses like influenza and SARS-CoV-2 evolve rapidly while others are stable. Dr. Kistler explained that “some of the factors that influence antigen evolution include mutation rates, mutational tolerance of proteins targeted by neutralizing antibodies, the location and codominance of epitopes, viral transmission dynamics, and existing herd immunity. force.”

Dr. Kistler said that while “antigenic evolution is not common but not uncommon among endemic viruses, immune evasion appears to be a major driver of continued adaptation in viruses that have circulated in humans for decades or longer.” . Because viruses that evolve these antigens are “particularly capable of causing superinfections and evading vaccine-mediated immunity,” determining which viruses evolve in this way and how quickly they evolve is “directly relevant to vaccine design.” She added, “For example, the strains included in influenza vaccines must be regularly updated to antigenically match circulating strains. Vaccines targeting any antigenically evolving proteins will likely have to do the same.” Looking ahead, Kister Dr. Le aims to “further extend this work to compare a wider range of endemic viruses. The pandemic has fueled interest in sequencing circulating viruses, and we hope to be able to analyze more viruses in the future.”

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