NS1' of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness.
Flavivirus NS1 is a nonstructural protein involved in virus replication and regulation of the innate immune response. Interestingly, a larger NS1-related protein, NS1', is often detected during infection with the members of the Japanese encephalitis virus serogroup of flaviviruses. However, how NS1' is made and what role it performs in the viral life cycle have not been determined. Here we provide experimental evidence that NS1' is the product of a -1 ribosomal frameshift event that occurs at a conserved slippery heptanucleotide motif located near the beginning of the NS2A gene and is stimulated by a downstream RNA pseudoknot structure. Using site-directed mutagenesis of these sequence elements in an infectious clone of the Kunjin subtype of West Nile virus, we demonstrate that NS1' plays a role in viral neuroinvasiveness.
Melian
Ezequiel Balmori
EB
Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
Hinzman
Edward
E
Nagasaki
Tomoko
T
Firth
Andrew E
AE
Wills
Norma M
NM
Nouwens
Amanda S
AS
Blitvich
Bradley J
BJ
Leung
Jason
J
Funk
Anneke
A
Atkins
John F
JF
Hall
Roy
R
Khromykh
Alexander A
AA
D000595:Amino Acid Sequence; D001483:Base Sequence; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D018965:Frameshifting, Ribosomal; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
C100315:NS1 protein, Flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins