Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
| Autor: | Saket Choudhary, Patrick C. Wilson, Aeron C. Hurt, Scott E. Hensley, Terry Stevens-Ayers, Seema S. Lakdawala, Juhye M. Lee, Trevor Bedford, Rachel Eguia, Jesse D. Bloom, Seth J. Zost, Michael Boeckh |
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| Rok vydání: | 2019 |
| Předmět: |
Serum
0301 basic medicine viruses Hemagglutinin Glycoproteins Influenza Virus Antibodies Viral influenza virus Epitope Neutralization 0302 clinical medicine deep mutational scanning Biology (General) Microbiology and Infectious Disease 0303 health sciences education.field_of_study General Neuroscience General Medicine Orthomyxoviridae Virus 3. Good health Viral evolution Medicine Research Article Human QH301-705.5 Science Population Hemagglutinin (influenza) Biology General Biochemistry Genetics and Molecular Biology Antigenic drift 03 medical and health sciences Orthomyxoviridae Infections Immunity Influenza Human Animals Humans hemagglutinin education Immune Evasion antigenic drift 030304 developmental biology Evolutionary Biology General Immunology and Microbiology Ferrets Genetic Variation Virology 030104 developmental biology Polyclonal antibodies Mutation mutational antigenic profiling biology.protein 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 8 (2019) eLife |
| DOI: | 10.1101/670497 |
| Popis: | A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility. eLife digest The human immune system protects the body from repeat attacks by remembering past infections. However, a typical person comes down with the flu every five to seven years. This is because flu viruses rapidly evolve to bypass our defenses. So, after a few years, the viruses look so different that the immune system no longer recognizes them. The immune system recognizes flu viruses by producing proteins known as antibodies, which can bind to the virus and prevent it from infecting cells. Many of these antibodies bind to a protein on the surface of the virus called hemagglutinin, but each anti-flu antibody recognizes only a small region of the protein. This means that to escape recognition by a single antibody, all the virus needs to do is wait for a lucky mutation to change the part of hemagglutinin recognized by that antibody. But humans make many different antibodies. To escape them all, flu viruses would need lots of lucky mutations. So how do flu viruses keep winning the evolutionary lottery? To answer this question, Lee et al. made all the possible individual mutations to the hemagglutinin protein of a human flu virus. A pool of these viruses was then exposed to the full mix of antibodies present in human serum (the liquid component of blood). Lee et al. then checked which mutations helped the virus survive contact with the antibodies. For most human serum samples, a single mutation was enough to allow the virus to escape most of one person’s anti-flu antibodies. This suggests that the immune response to flu is so focused on a small region of hemagglutinin that a mutation in this region can enable the virus to take a huge step towards evading immune detection. Even more surprising was what happened when Lee et al. looked at serum from different people. A mutation that helped the virus to escape immune detection in one person often had little or no effect on escape from another person’s immunity. In other words, the lucky mutation that the virus needed to escape differed from one person to the next. Every year there are many related flu viruses that infect humans. The results of Lee et al. suggest that people could be susceptible to different forms of the virus. Understanding how flu viruses escape immune detection in different people could help us identify which version of the virus different people are more susceptible to, and perhaps eventually better predict how the virus will evolve and spread. |
| Databáze: | OpenAIRE |
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