Researchers from the Institute of Integrative Systems Biology (I2SysBio), a joint centre of the University of Valencia and the Spanish National Research Council (CSIC), have studied the mechanism by which the body’s antibodies target coxsackievirus B3, which causes serious heart inflammation in humans. The work, published in the journal Nature Communications , has been developed with mice and human sera, reveals 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 constitute 40% of all mammalian viruses and are an important cause of disease in humans. Neutralising antibodies play a key role in resolving viral infections and confer protection against reinfection. To successfully infect and spread, viruses must overcome neutralising antibodies by mutating their target, which is the viral capsid. It is unknown how neutralising antibodies present in 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 their frequency with high resolution. The result shows for the first time how polyclonal sera (antibodies circulating in blood) target the virus and how it can escape neutralisation.
Specifically, they show that the response of these antibodies in immunised laboratory mice 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 harbouring mutations that escape neutralisation 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.
"We provide the first comprehensive analysis of how the capsid of a non-enveloped virus is targeted by antibodies in sera from immunised 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 neutralisation requires multiple mutations, but comes at a cost to viral fitness".
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