title: Genetic analysis of attenuation markers of cold-adapted X-31 influenza live vaccine donor strain.
abstract: Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics.
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors: Yo Han
authors: YH
authors: Jang
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors: Eun-Ju
authors: EJ
authors: Jung
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors: Kwang-Hee
authors: KH
authors: Lee
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors: Young Ho
authors: YH
authors: Byun
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors: Seung Won
authors: SW
authors: Yang
authors: Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea; Vaccine Translational Research Center, Yonsei University, Seoul, South Korea. Electronic address: blseong@yonsei.ac.kr.
authors: Baik Lin
authors: BL
authors: Seong
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D003080:Cold Temperature; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus / Q000235:genetics*; D007252:Influenza Vaccines; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D016865:Reassortant Viruses / Q000235:genetics*; D016415:Sequence Alignment; D014613:Vaccines, Attenuated; D010948:Viral Plaque Assay
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: Cold-adapted live vaccine; Influenza virus; Nucleoprotein; Phenotype; X-31