title: Genomic polymorphism of the pandemic A (H1N1) influenza viruses correlates with viral replication, virulence, and pathogenicity in vitro and in vivo.
abstract: The novel pandemic A (H1N1) virus was first identified in Mexico in April 2009 and quickly spread worldwide. Like all influenzas, the H1N1 strain-specific properties of replication, virulence, and pathogenicity are a result of the particular genomic sequence and concerted expression of multiple genes. Thus, specific mutations may support increased virulence and may be useful as biomarkers of potential threat to human health. We performed comparative genomic analysis of ten strains of the 2009 pandemic A (H1N1) influenza viruses to determine whether genotypes associated with clinical phenotypes, which ranged from mild to severe illness and up to lethal. Virus replication capacity was tested for each strain in vitro using cultured epithelial cells, while virulence and pathogenicity were investigated in vivo using the BALB/c mouse model. The results indicated that A/Sichuan/1/2009 strain had significantly higher replication ability and virulence than the other strains, and five unique non-synonymous mutations were identified in important gene-encoding sequences. These mutations led to amino acid substitutions in HA (L32I), PA (A343T), PB1 (K353R and T566A), and PB2 (T471M), and may be critical molecular determinants for replication, virulence, and pathogenicity. Our results suggested that the replication capacity in vitro and virulence in vivo of the 2009 pandemic A (H1N1) viruses were not associated with the clinical phenotypes. This study offers new insights into the transmission and evolution of the 2009 pandemic A (H1N1) virus.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhou
authors.forename: Dayan
authors.initials: D
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Yila
authors.initials: Y
authors.lastname: Ma
authors.forename: Fengdi
authors.initials: F
authors.lastname: Li
authors.forename: Huihui
authors.initials: H
authors.lastname: Sun
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Ma
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004285:Dogs; D005260:Female; D016679:Genome, Viral; D066298:In Vitro Techniques; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D014774:Virulence / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D017931:DNA Primers