Grant: Project Grant

Enteroviruses are an important group of pathogens causing a range of diseases in humans including poliomyelitis, meningitis, encephalitis, conjunctivitis and myocarditis. While poliomyelitis is almost eradicated worldwide, other enteroviruses cause millions of infections every year, especially in children. Approved vaccines and antivirals are not available against most enterovirus diseases. Due to limited protein coding capacity of their genomes, enteroviruses depend extensively on host factors and pathways during replication. Host factors with conserved functions among enteroviruses could serve as attractive targets to develop antivirals. Recently, over 7000 novel small open reading frames were discovered in the human genome, that encode proteins termed 'microproteins' that are less than 100 amino acids long. How these microproteins affect viral infections are completely unknown. Our preliminary studies have identified and validated microproteins that support or restrict enterovirus replication in cells. The biological functions of these microproteins and how they modulate virus replication is currently unclear. Our study aims to investigate the mechanism of action of microproteins involved in enterovirus replication and examine the conserved role of microproteins in the life cycle of important human enteroviruses. Identifying novel druggable microprotein targets conserved among enteroviruses may lead to development of broad-spectrum antivirals.