The polypyrimidine tract-binding protein is required for efficient dengue virus propagation and associates with the viral replication machinery.
The polypyrimidine tract-binding protein (PTB) functions primarily as an IRES trans-acting factor in the propagation of hepatitis C virus and picornaviruses. PTB interacts with secondary structures within the 3'- and 5'-untranslated regions of these viral genomes to mediate efficient IRES-mediated viral translation. PTB has also been reported to bind to the untranslated region of the single-stranded RNA dengue virus (DENV), suggesting a similar function for PTB in flaviviruses. Indeed small interfering RNA-mediated PTB knockdown inhibited the production of infectious DENV, and this inhibition was specific to PTB knockdown and not due to a nonspecific anti-viral state. In fact, PTB depletion did not inhibit the production infectious yellow fever virus, another flavivirus. Nevertheless, whereas PTB knockdown led to a significant decrease in the accumulation of DENV viral RNAs, it did not impair translation. Moreover, PTB was shown to interact with the DENV nonstructural 4A protein, a known component of the viral replication complex, and with the DENV genome during infection. These data suggest that PTB interacts with the replication complex of DENV and is acting at the level of viral RNA replication.
Anwar
Azlinda
A
From the Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 169547.
Leong
K M
KM
From the Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 169547.
Ng
Mary L
ML
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Chu
Justin J H
JJH
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. Electronic address: miccjh@nus.edu.sg.
Garcia-Blanco
Mariano A
MA
From the Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 169547; Duke University Medical Center, Durham, North Carolina 27710. Electronic address: garci001@mc.duke.edu.
D000330:Aedes; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D015005:Yellow fever virus / Q000472:pathogenicity / Q000502:physiology
C080106:NS4A protein, flavivirus; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D038941:Polypyrimidine Tract-Binding Protein