Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin

• Published in: eLife Vol. 7
• Main Authors: Phillips, Angela M, Doud, Michael B, Gonzalez, Luna O, Butty, Vincent L, Lin, Yu-Shan, Bloom, Jesse D, Shoulders, Matthew D
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 06.09.2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Amino Acid Sequence; Amino acids; Antibodies; Biochemistry and Chemical Biology; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress - genetics; Evolution; Evolutionary Biology; Fever; Gene Expression Profiling; Genetic aspects; Haplotypes; HEK293 Cells; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinins; Humans; Immunological tolerance; Influenza; Lectins; membrane protein; Membrane proteins; Mutation; Protein folding; Proteins; Proteostasis; Quality control; Regression analysis; Secretory Pathway - genetics; Temperature; Temperature tolerance; Tetracyclines; unfolded protein response; Unfolded Protein Response - genetics; United States > US; Massachusetts; influenza; unfolded protein response; evolutionary biology; chemical biology; biochemistry; membrane protein; protein folding; evolution; proteostasis; human; virus

We systematically and quantitatively evaluate whether endoplasmic reticulum (ER) proteostasis factors impact the mutational tolerance of secretory pathway proteins. We focus on influenza hemaggluttinin (HA), a viral membrane protein that folds in the host's ER via a complex pathway. By integrat...