start-ver=1.4
cd-journal=joma
no-vol=430
cd-vols=
no-issue=2
article-no=
start-page=592
end-page=597
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PML tumor suppressor protein is required for HCV production
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.
en-copyright=
kn-copyright=

en-aut-name=KurokiMisao
en-aut-sei=Kuroki
en-aut-mei=Misao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AriumiYasuo
en-aut-sei=Ariumi
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HijikataMakoto
en-aut-sei=Hijikata
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IkedaMasanori
en-aut-sei=Ikeda
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WakitaTakaji
en-aut-sei=Wakita
en-aut-mei=Takaji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShimotohnoKunitada
en-aut-sei=Shimotohno
en-aut-mei=Kunitada
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatoNobuyuki
en-aut-sei=Kato
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Kyoto Univ, Dept Viral Oncol, Inst Virus Res

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Natl Inst Infect Dis, Dept Virol 2

affil-num=7
en-affil=
kn-affil=Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci
en-keyword=Hepatitis C virus
kn-keyword=Hepatitis C virus
en-keyword=PML
kn-keyword=PML
en-keyword=INI1
kn-keyword=INI1
en-keyword=DDX5
kn-keyword=DDX5
en-keyword=Tumor suppressor
kn-keyword=Tumor suppressor
en-keyword=Lipid droplet
kn-keyword=Lipid droplet
END