The adaptive immunity of human endemic viruses

In a recent study posted to the bioRxiv* preprint server, researchers analyzed the viral genomes of 28 endemic viruses to study the evolution of the ability of viruses to evade the neutralizing antibodies elicited by vaccines or previous infections.

Study: An Atlas of Adaptive Evolution in Endemic Human Viruses. Image Credit: Inkoly/Shutterstock.comStudy: An Atlas of Adaptive Evolution in Endemic Human Viruses. Image Credit: Inkoly/

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


Viruses evolve rapidly and adapt to changing environments due to their high mutation rates and low generation time. Often viruses adapted to different animal hosts infect humans and optimize the methods through which they enter and replicate in the host cell, increasing the human-to-human transmission and evolving into a novel pathogen.

The early stages of pandemics are often characterized by high adaptive evolutionary rates, as was seen during the coronavirus disease 2019 (COVID-19) pandemic and outbreaks related to various other respiratory viruses.

While some viruses become endemic after adapting to a new host and do not evolve further, other endemic viruses continue to adapt through antigenic evolution, resulting in an arms race between the virus and the human immune system.

Since viruses that undergo antigenic evolution pose the risk of repeat infections and increase their ability to evade vaccine-induced immunity, understanding which viruses continue to undergo antigen evolution could help manage future disease outbreaks.

About the study

The present study used sequence data for each gene in 28 viral genomes to estimate adaptive evolutionary rates. These 28 viruses spanned ten families and were transmitted between humans through various modes.

Viruses with potentially high antigenic evolution rates were identified based on the high evolutionary rates for the genes coding for receptor-binding proteins since the receptor-binding region is involved in antibody neutralization and harbors most mutations that allow antigenic escape.

The adaptive evolutionary rates were calculated in terms of the number of adaptive mutations in each codon per year, which allowed the adaptive evolutionary rates to be compared across the various genes in the genome and across viruses.

The adaptive evolutionary rates of three viruses that were known to undergo antigenic evolution — coronavirus 229E, influenza viruses A/H3N2, and influenza viruses B/Yam — were compared against the evolutionary rates of three antigenically stable viruses, hepatitis A, measles, and influenza C/Yamagata.

To understand the patterns of adaptive evolution in recent years, the sequence data for 28 viruses that are pathogenic to humans were obtained and curated. These viruses included deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) viruses and were transmitted between humans through bodily fluids, blood, vectors, fecal-oral, and respiratory routes.

The researchers only investigated endemic viruses since they were interested in understanding the antigenic evolution that occurs during the endemic phase and not the initial adaptive phase.

The evolutionary rates of the receptor binding protein, which was expected to be highly variable across endemic viruses, and the polymerase gene, which was expected to be conserved, were compared across the 28 viruses.

Since the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been relatively recent, and the Omicron variant carried a large number of mutations indicating a single fixation event, SARS-CoV-2 was compared with ten other antigenically evolving viruses by comparing the amino-acid substitution rates in the receptor binding protein.


The results reported that 10 of the 28 viruses undergo adaptive evolution resulting in the antigenic mutations that allow the viruses to escape the immunity induced by previous infections and vaccines.

Furthermore, comparing amino-acid substitution rates between SARS-CoV-2 and other viruses revealed that SARS-CoV-2 is evolving and accumulating mutations that cause protein-coding changes at rates much higher than other endemic viruses.

Antigenic evolution was found to be more prevalent in RNA viruses. Still, the researchers believe that since the list of viruses included in the study was not comprehensive and comprised only well-studied viruses, determining the proportion of antigenically evolving endemic viruses is difficult.

Furthermore, the rate of adaptive mutations might not reflect the phenotypic changes occurring in the viruses, implying that viruses with receptor-binding protein genes that evolve at the same rates might not develop the ability to evade vaccine or infection-induced immunity at the same rates.


Overall, the findings suggested that many human viruses that have become endemic continue to evolve antigenically, gaining the ability to escape the neutralizing antibodies generated by vaccinations or previous infections.

Ten of the 28 viruses investigated in this study showed continued adaptive evolution. In contrast, the amino-acid substitution rates showed that SARS-CoV-2 is evolving faster than the other ten endemic human viruses.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.


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