title: Analysis of the beta-propiolactone sensitivity and optimization of inactivation methods for human influenza H3N2 virus.
abstract: Beta-propiolactone (BPL) is used as an inactivating reagent for influenza virus in a number of countries. However, the treatment of viruses with BPL occasionally results in a decrease in the hemagglutinin (HA) titer, which complicates vaccine development. In the present study, we examined the biological and biochemical characteristics of human H1N1 and H3N2 viruses treated with BPL, and developed an inactivation method for BPL-sensitive viruses. A significant decrease in HA titer was detected in the H3N2 viruses examined. The decrease in the pH of the virus fluid was not associated with the decreased HA titer, indicating that the decrease in HA titer for the H3N2 virus is the result of the direct effect of BPL. Excessive modification of M1 by BPL and loss of virion diameter were observed in 0.1% BPL-treated H3N2 virus. Taken together, these results suggest that the BPL sensitivity of H3N2 virus results from disruption of the virion. By contrast, the H3N2 virus was successfully inactivated by 0.02% BPL without a significant decrease in the HA titer or disruption of virion structure. Furthermore, we found that the 0.02% BPL in the virion preparation was hydrolyzed successfully by incubation at 37°C for 7h. Thus, mild treatment with a low concentration of BPL enabled us to inactivate the H3N2 virus.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yoshino
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Sato
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Japan. Electronic address: ymuraki@iwate-med.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Muraki
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D006868:Hydrolysis; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000648:ultrastructure; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000648:ultrastructure; D061985:Madin Darby Canine Kidney Cells; D011420:Propiolactone / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects; D038301:Virus Inactivation
chemical_list: D011420:Propiolactone
keywords: Beta-propiolactone; Inactivation; Influenza virus; Virion size