Effects of the C-terminal truncation in NS1 protein of the 2009 pandemic H1N1 influenza virus on host gene expression.
The 2009 pandemic H1N1 influenza virus encodes an NS1 protein with 11 amino acids (aa) truncation at the C-terminus. The C-terminal tail of influenza virus NS1 protein constitutes a nucleolar localization signal (NoLS) and is the binding domain of the cellular pre-mRNA processing protein, poly(A)-binding protein II (PABII). Here, our studies showed that the C-terminal-truncated NS1 of the 2009 pandemic virus was inefficient at blocking host gene expression, extension of the truncated NS1 to its full length increased the inhibition of host gene expression. Mechanistically, this increased inhibition of host gene expression by the full-length NS1 was not associated with nucleolar localization, but was due to the restoration of NS1's binding capacity to PABII. Furthermore, in vitro and in vivo characterization of two recombinant viruses encoding either the C-terminal 11-aa truncated or full-length NS1 of the 2009 pandemic virus showed that the C-terminal 11-aa truncation in NS1 did not significantly alter virus replication, but increased virus pathogenicity in mice.
Unit of Animal Infectious Diseases, National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.
Jiagang
J
Tu
Jing
J
Guo
Anding
A
Zhang
Wenting
W
Zhang
Zongzheng
Z
Zhao
Hongbo
H
Zhou
Cheng
C
Liu
Huanchun
H
Chen
Meilin
M
Jin
D000818:Animals; D002460:Cell Line; D004285:Dogs; D005786:Gene Expression Regulation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009976:Orthomyxoviridae Infections / Q000821:virology; D058873:Pandemics; D039103:Poly(A)-Binding Protein II / Q000378:metabolism; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D034421:Sus scrofa; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*
C085820:INS1 protein, influenza virus; D039103:Poly(A)-Binding Protein II; D017361:Viral Nonstructural Proteins