Innate immune recognition of a general protein pattern on virus capsids triggers an anti-viral immune response
Quick and specific identification of an invading pathogen is critical for the initiation of a pathogen-specific immune response that aids in killing the pathogen and preventing disease.
There are many ways the immune system can identify pathogens. Viruses, like the flu, are known to stimulate an immune response after they have begun infection. These immune responses are specific to each individual virus and can involve very different pathways depending on the virus. However, whether there is a common external factor among viruses that tells our immune system we are in danger remains unknown. These unknowns are important to determine as viruses, specifically influenza, remain a global problem.
Between 291,000 and 646,000 people die globally each year from influenza and secondary bacterial infections, some comprising anti-biotic resistant bacteria, are involved in many of these cases. Therefore, it is important to better understand these unknowns to determine new or more specific ways to fight them.
In this paper, led by lab postdoc Kelly Shepardson in collaboration with [then] graduate student Benjamin Schwarz (Trevor Douglas lab, IU), we explore the complex nature of how viruses are initially recognized. Our results reveal that the repeating protein pattern, common to the external surface of a virus (capsid), regulates susceptibility to secondary bacterial infections over time.
Importantly, this pattern recognition is independent of virus infection and can be induced by proteins with similar patterns, independent of shape, size, and protein composition. This early response to the virus and bacterial susceptibility is driven by recognition of the repeating protein pattern by a protein located on the cell surface involved in pathogen recognition, TLR2 (toll like receptor 2).
The implication of this research is that since the repeating protein subunit pattern is conserved across viral capsids, it suggests it is not easy for a virus to change without altering its fitness. Targeting this vulnerability could lead to augmentation or development of a universal anti-viral vaccine.