Classical swine fever virus NS5A regulates viral RNA replication through binding to NS5B and 3'UTR.
In this report, classical swine fever virus (CSFV) NS5A inhibit viral RNA replication when its concentration reached and surpassed the level of NS5B. Three amino acid fragments of CSFV NS5A, 137-172, 224-268 and 390-414 individually were shown to be essential to NS5B binding. The former two fragments were independently necessary for regulation of viral RNA replication and correlated with NS5B and 3'UTR binding activity. We also found that amino acids W143, V145, P227, T246, P257, K399, T401, E406 and L413 of CSFV NS5A were essential to NS5B binding activity. Furthermore, these amino acids were shown to be necessary for viral RNA replication and infection and conserved in NS5A proteins of CSFV, BDV, BVDV and HCV. These results indicated that NS5A may regulate viral RNA replication by binding to NS5B and 3'UTR. NS5A can still regulate viral RNA synthesis through binding to 3'UTR when binding to NS5B is not available.
Biology Department, College of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234, China.
Yan
Y
Chen
Jun
J
Xiao
Jing
J
Xiao
Chun
C
Sheng
Jing
J
Wang
Lin
L
Jia
Yimiao
Y
Zhi
Guangyuan
G
Li
Jun
J
Chen
Ming
M
Xiao
D020413:3' Untranslated Regions / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004252:DNA Mutational Analysis; D015967:Gene Expression Regulation, Viral; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
D020413:3' Untranslated Regions; C096041:NS5 protein, flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins