Selection pressure in the human adenovirus fiber knob drives cell specificity in epidemic keratoconjunctivitis

摘要: ABSTRACT Human adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism some but not all HAdV-Ds are known. fiber protein is major capsid protein; its C-terminal “knob” mediates binding host cell receptors facilitate subsequent viral entry. In comprehensive phylogenetic analysis of genes, knob gene sequences types EKC formed unique clade. By proteotyping analysis, virus-associated knobs were uniquely shared. Comparative structural modeling showed no distinct variations in did show variation among region overlapping the known CD46 site HAdV-B. We also found signature amino acid positions that distinguish from non-EKC types, and by vitro studies we epithelial can be predicted presence lysine or alanine at residue 240. This same shows evidence positive selection, suggesting evolutionary pressure enhances fitness infection, may molecular determinant pathogenesis. IMPORTANCE Viruses adapt various survival strategies gain entry into target cells. adenovirus (HAdV) conditions, yet connections between genotype cellular generally lacking. Here, provide basis association genotypes within HAdV D keratoconjunctivitis, find genes pathogens, specifically region, share Deeper revealed crucial sites has significant impact on conformation, which likely important Specific acids hot spot residues link possibly pathogenesis.