Influenza virus ts61S hemagglutinin is significantly defective in polypeptide folding and intracellular transport at the permissive temperature.
The influenza virus hemagglutinin (HA) temperature-sensitive (ts) mutant, ts61S, contains a nucleotide change in RNA segment 4 which leads to an amino acid change at HA1 residue 110 of serine to proline. When ts61S HA is synthesized and maintained at the nonpermissive temperature (39.5 degrees), the HA is defective in transport in the exocytic pathway and is retained in the endoplasmic reticulum (S. Nakajima, D. J. Brown, M., Ueda, K., Nakajima, A. Suguira, A. K. Pattnaik, and D. P. Nayak, 1986, Virology 154, 279-285). In a comparison of the biochemical properties of ts61S HA and A/WSN/33 HA (wt) expressed at the permissive temperature (33 degrees), we have found that ts61S HA is extensively debilitated. A large proportion of ts61S HA fails to gain reactivity with conformation-specific monoclonal antibodies and does not become resistant to protease digestion. In turn, a large population of the molecules are not transported from the ER to the Golgi apparatus or cell surface with the same kinetics or efficiency as wt HA. These data suggest that the serine to proline change at HA1 residue 110 leads to partial impairment of folding at the permissive temperature with complete impairment at the nonpermissive temperature.
Simpson
D A
DA
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500.
Lamb
R A
RA
D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D005089:Exocytosis; D005455:Fluorescent Antibody Technique; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000096:biosynthesis / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D007700:Kinetics; D009154:Mutation; D011392:Proline; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012694:Serine; D013696:Temperature; D014759:Viral Envelope Proteins / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D014759:Viral Envelope Proteins; D012694:Serine; D011392:Proline