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2018 ; 28
(3
): 200-208
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Modulation of mRNA Translation and Cell Viability by Influenza A Virus Derived
Nonstructural Protein 1
#MMPMID29634401
Liu Y
; Chia ZH
; Liew JNMH
; Or SM
; Phua KKL
Nucleic Acid Ther
2018[Jun]; 28
(3
): 200-208
PMID29634401
show ga
Translation of in vitro transcribed messenger RNA (mRNA) is known to be
compromised by cell's innate immune responses. Herein we show that when mRNA
encoding nonstructural protein 1 (NS1), an immune evasion gene derived from
influenza A virus, is co-delivered with mRNA encoding green fluorescent protein
(GFP), higher GFP expression can be observed in four different interferon
competent cell types within 6?h, indicating NS1's wide host range property and
rapid counter response to the cells' innate immune response. Enhanced mRNA
translation correlates with reduced interferon production in all tested cell
types and substituting a small portion of luciferase mRNA with NS1 mRNA enhances
luciferase production compared to the same dose composing of only luciferase mRNA
although in a cell type specific manner. Toxicity caused by transfection of
unmodified mRNA is mitigated with the delivery of NS1 mRNA and is observed only
in NS1 without cleavage and polyadenylation specificity factor 30 kda (CPSF30)
inhibition function. Conversely, delivery of mRNA encoding NS1 with CPSF30
inhibition function aggravated toxicity. Overall, we demonstrate that NS1
enhanced mRNA transfection through active evasion of innate immune responses and
modulated cellular viability during mRNA transfection.
|*Gene Expression Regulation, Viral
[MESH]
|*Immune Evasion
[MESH]
|Animals
[MESH]
|Cell Line
[MESH]
|Cell Survival
[MESH]
|Chlorocebus aethiops
[MESH]
|Cleavage And Polyadenylation Specificity Factor/genetics/immunology
[MESH]
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