title: Molecular basis of live-attenuated influenza virus.
abstract: Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular) response that represents a naturally occurring transient infection. The cold-adapted (ca) influenza A/AA/6/60 (H2N2) (AA ca) virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47) along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8), we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Huamin
authors.initials: H
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000502:physiology; D007252:Influenza Vaccines / Q000235:genetics* / Q000627:therapeutic use; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000235:genetics* / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D007252:Influenza Vaccines; C057027:PB2 protein, Influenzavirus A; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase
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