title: Persistent infection with influenza A virus: evolution of virus mutants.
abstract: A persistent infection (persistent infection I) of baby hamster kidney (BHK) cells with the WSN (H1N1) strain of influenza A virus was established using a virus stock which contained a high proportion of defective-interfering (DI) particles. Virus recovered from passage 92 (388 days) of persistent infection I was used to establish a second persistent infection (persistent infection II) in BHK cells. A number of phenotypic changes were identified in the virus isolated during the first 50 passages of persistent infection I (early pi virus). These included a decrease in the size of plaques, the appearance of temperature-sensitive mutants, and a decreased ability of amplified pi virus to agglutinate chicken erythrocytes. The decreased ability to cause hemagglutination was associated with a 20- to 30-fold increase in viral neuraminidase activity. Virus isolated after passage 63 of persistent infection I could not be amplified in eggs or in a number of cell lines. Although very little infectious virus was produced when cells were infected with these late pi viruses, cytopathology frequently occurred and an unusual pattern of viral protein synthesis was observed. The NP protein was the predominant protein synthesized, while the synthesis of M protein was drastically reduced relative to its synthesis in cells infected with parental WSN virus. The HA, NS1, and NS2 proteins were not detected; however, a virus-specific protein which migrates faster than NS2 was observed. Virus recovered from persistent infection II interfered with the replication of parental WSN virus in a mixed infection. The pattern of protein synthesis in such mixed infections resembled that in cells singly infected with late pi virus. DI particles did not appear to play a significant role either in the maintenance of the persistent infection, in the expression of the pi protein synthesis phenotype, or in the pi virus-mediated interference.
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002472:Cell Transformation, Viral; D006224:Cricetinae; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D009980:Influenza A virus / Q000235:genetics* / Q000302:isolation & purification; D007668:Kidney; D009154:Mutation; D009439:Neuraminidase; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification
chemical_list: D014764:Viral Proteins; D009439:Neuraminidase