(From left to right). Javier Buceta, Beatriz Álvarez-Rodríguez and Ron Geller.

Research staff at the Institute of Integrative Systems Biology (I2SysBio), a joint center of the University of Valencia and the Higher Council for Scientific Research (CSIC), have studied the mechanism by which the body's antibodies are directed against coxsackievirus B3, which causes severe inflammation of the heart in humans. The work, published in the journal Nature Communications, has been developed with serum from mice and humans, allowing us to understand how antibodies interact with viruses and how the latter can evolve to evade the immune response. Additionally, it is the first comprehensive analysis of how human sera target a non-enveloped virus.

Non-enveloped viruses comprise 40% of all mammalian viruses and are an important cause of disease in humans. Neutralizing antibodies are essential to resolve viral infections and confer protection against reinfection. To successfully infect and spread, viruses must overcome neutralizing antibodies by mutating their target, which is the viral capsid. It is unknown how neutralizing antibodies present in the blood attack viral capsids.

The work of Beatriz Álvarez-Rodríguez, Javier Buceta and Ron Geller, useful for the design of therapeutic interventions and vaccines, has introduced a large number of mutations in the capsid, the protein shell of the virus that encloses its genetic material, and has tracked its frequency with high resolution. The result shows for the first time how polyclonal sera (antibodies that circulate in the blood) target the virus and how it can escape neutralization. Specifically, they show that the response of these antibodies in immunized laboratory mice It is directed to a single region of the viral capsid, while the sera generated by the human organism present varied responses that are directed to one or several different regions. Additionally, the authors have generated a panel of viruses harboring mutations that escape neutralization and used them to define which regions of the viral capsid are targeted in a large sample of sera, uncovering unexpected conservation in human responses. 137.4pt 183.2pt 229.0pt 274.8pt 320.6pt 366.4pt 412.2pt 458.0pt 503.8pt 549.6pt 595.4pt 641.2pt 687.0pt 732.8pt">“We provide the first complete analysis of how the capsid of a non-enveloped virus is neutralized by antibodies present in sera from immunized mice and from naturally acquired infections in humans,” explains Ron Geller. Furthermore, "we defined the predominance of capsid regions targeted by human sera and found that almost all sera target the same region. We have also found that escaping neutralization requires multiple mutations, but comes at a cost to the virus."

This work is supported by the Ministry of Science and Innovation, the Generalitat Valenciana, the Newt Generation and ERDF funds of the European Union. Also from the European Virus Archive (EVAg) and the Príncipe Felipe Research Center. style="color:black">

Article reference: Álvarez-Rodríguez, B., Buceta, J. & Geller, R. "Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3." Nat Commun 14, 6417 (2023). https://doi.org/10.1038/s41467-023-42144-2