title: The cytoplasmic tails of the influenza virus spike glycoproteins are required for normal genome packaging.
abstract: Deletion of the cytoplasmic tails of the influenza A virus spike glycoproteins, hemagglutinin (HA) and neuraminidase (NA), has previously been shown to result in markedly defective virion morphogenesis (Jin et al., 1997, EMBO J. 16, 1236-1247). We have found that influenza A virus preparations lacking the HA and NA cytoplasmic tails (HAt-/NAt-) have a reduced vRNA to protein content, contain an increase in cellular RNA contaminants, and exhibit increased resistance to ultraviolet (UV) inactivation. There is also a direct correlation between abnormal virion morphology and reduced infectivity. The data suggest that the HAt-/NAt- virion population contains a broader range of number of packaged RNA segments than wild-type (wt) virus. Sucrose gradient centrifugation analysis indicated the presence of a subpopulation of virions with pronounced deformation in virion morphology and reduced infectivity. The role of the HA and NA cytoplasmic tails was examined further by using a trans-complementation assay and it was found that expression of wt HA and NA from cDNAs followed by HAt-/NAt- virus infection caused the formation of a pseudotype virus with wt sedimentation properties. Taken together the data indicate that the HA and NA cytoplasmic tails affect not only virion morphology but also proper genome packaging.
authors.affiliation: Department of Biochemistry, Northwestern University, Evanston, Illinois, 60208-3500, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: G P
authors.initials: GP
authors.lastname: Leser
authors.forename: A
authors.initials: A
authors.lastname: Pekosz
authors.forename: R A
authors.initials: RA
authors.lastname: Lamb
mesh_terms: D000818:Animals; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003593:Cytoplasm; D004285:Dogs; D016679:Genome, Viral; D006388:Hemagglutinins / Q000502:physiology*; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology*; D008854:Microscopy, Electron; D009439:Neuraminidase / Q000502:physiology*; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014771:Virion / Q000737:chemistry; D019065:Virus Assembly
chemical_list: D006388:Hemagglutinins; D009439:Neuraminidase