Title |
Molecular characterization of mammalian-adapted Korean-type avian H9N2 virus and evaluation of its virulence in mice |
Author |
Kuk Jin Park1, Min-Suk Song1, Eun-Ha Kim1, Hyeok-il Kwon1, Yun Hee Baek1, Eun-hye Choi1, Su-Jin Park1, Se Mi Kim1, Young-il Kim1, Won-Suk Choi1, Dae-Won Yoo2, Chul-Joong Kim2, and Young Ki Choi1* |
Address |
1College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea, 2College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, Republic of Korea |
Bibliography |
Journal of Microbiology, 53(8),570-577, 2015,
|
DOI |
10.1007/s12275-015-5329-4
|
Key Words |
influenza A virus, H9N2, mammalian adaptation,
reverse genetic method, virulence marker |
Abstract |
Avian influenza A virus (AIV) is commonly isolated from
domestic poultry and wild migratory birds, and the H9N2
subtype is the most prevalent and the major cause of severe
disease in poultry in Korea. In addition to the veterinary concerns
regarding the H9N2 subtype, it is also considered to
be the next potential human pandemic strain due to its rapid
evolution and interspecies transmission. In this study, we
utilize serial lung-to-lung passage of a low pathogenic avian
influenza virus (LPAI) H9N2 (A/Ck/Korea/163/04, WT163)
(Y439-lineage) in mice to increase pathogenicity and investigate
the potential virulence marker. Mouse-adapted H9N2
virus obtained high virulence (100% mortality) in mice after
98 serial passages. Sequence results show that the mouse
adaptation (ma163) possesses several mutations within seven
gene segments (PB2, PA, HA, NP, NA, M, and NS) relative
to the wild-type strain. The HA gene showed the most mutations
(at least 11) with one resulting in the loss of an N-glycosylation
site (at amino acid 166). Moreover, reverse genetic
studies established that an E627K substitution in PB2 and the
loss of the N-glycosylation site in the HA protein (aa166) are
critical virulence markers in the mouse-adapted H9N2 virus.
Thus, these results add to the increasing body of mutational
analysis data defining the function of the viral polymerase
and HA genes and their roles in mammalian host adaptation.
To our knowledge, this is first report of the generation
of a mammalian-adapted Korea H9N2 virus (Y493-lineages).
Therefore, this study offers valuable insights into the molecular
evolution of the LPAI Korean H9N2 in a new host and
adds to the current knowledge of the molecular markers associated
with increased virulence. |