UC San Diego

Viroporins are small multifunctional proteins that modify cellular membranes to facilitate viral infections such as viral nucleic acid entry and the release of virions from infected cells. We are interested in studying the evolutionary relationships among these proteins, in particular their organization into families and superfamilies. Comparative genomics analysis of 120 viral genomes, using the Phylogenetic Profiles method, allowed the identification of 12 families organized in four groups of functionally related families. Additionally, we compiled a list of 50 families from the Transporter Classification Database (TCDB) with viroporin-like attributes (i.e., length ≤ 300 aas, similar topology and/or documented viroporin activity). We then used TCDB as reference to search for homology signals among all 59 families using bioinformatic methods published by the Saier lab. These include (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) similarity of sequence profiles from multiple sequence alignments, (4) shared motifs, and (5) conserved domains. We were able to infer homology among 17 families, some of which expand the established Viral Envelope Fusion Protein Superfamily to include 7 families (TC: 1.G.9, 1.A.58, 1.A.19, 1.G.7, 1.A.40, 1.A.41 and 1.G.13), and the rest constitute three novel superfamilies: Viroporin-1 consists of three families (TC: 1.A.92, 1.A.93, and 1.A.94); Viroporin-2 is composed of two functionally-linked families (TC: 1.A.57 and 1.A.117); Viroporin-3 is composed of 3 functionally-related families (TC: 1.A.65, 1.A.99, and 1.A.116). We are confident that these results will be useful to the research community.