Cellular SRC kinases and dsRNA dependent protein kinase (PKR) play key role in intracellular viral (CVB3) replication

نویسندگان

  • M Zeinoddini
  • N Maghsoudi
چکیده مقاله:

SRC kinases and PKR are intracellular protein kinases, which play key roles in intracellular viral replication. In this research, the effect of SRC kinase inhibition and PKR activation and inhibition on replication of coxsakievirus (CVB3), an entrovirus of the family picornaviridae – causative agents of fatal myocarditis, was studied. Vero and Hela cells were cultured and infected with CVB3 in the presence of herbimycin A (specific tyrosin kinase inhibitor), added before and after infection in various time interval, gamma interferon (PKR activator) and 2-aminopurine (PKR inhibitor). Viral replication was monitored by molecular methods (RT-PCR) as well as plaque forming unit (PFU) count using a set of forward and reverse primer for viral gene, which could detect positive and negative strand mRNA of the virus, as well as PFU count. It was observed that SRC kinase inhibitor, when added before addition of CVB3 to the medium, can inhibit intracellular viral replication, whereas if herbimycin is added after infection, had no effect on viral proliferation. Using set of primers for conserved region of PKR gene, it was possible to observe the presence of PKR mRNA in all cultures either interferon treated, or 2Ap treated, or control. PFU studies showed that ?-INF has inhibitory effect on viral replication, where as 2Ap treatment enhanced viral replication. Relevance of the results towards development of new molecules for viral infection treatment will be discussed.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of Activation and Inhibition of Cellular PKR on Coxsackievirus B3 Replication

The ds-RNA activated protein kinase (PKR) is a serine-threonine kinase with MW of 68 KDa. It belongs to a family of kinases that control one of the translational initiation factors, eIF2. PKR is produced at high level in response to viral infection. This protein by phosphorylating eIF2 inhibits cellular protein synthesis. In this study, the effect of gamma interferon (IFN-γ), an activator, and ...

متن کامل

dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection

The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a). As such, P...

متن کامل

effect of activation and inhibition of cellular pkr on coxsackievirus b3 replication

the ds-rna activated protein kinase (pkr) is a serine-threonine kinase with mw of 68 kda. it belongs to a family of kinases that control one of the translational initiation factors, eif2. pkr is produced at high level in response to viral infection. this protein by phosphorylating eif2 inhibits cellular protein synthesis. in this study, the effect of gamma interferon (ifn-γ), an activator, and ...

متن کامل

Activation of dsRNA dependent protein kinase PKR in Karpas299 does not lead to cell death.

Activated double-stranded RNA (dsRNA)-dependent protein kinase PKR is a potent growth inhibitory protein that is primarily activated in virally infected cells, inducing them to die. We have recently shown that PKR can be selectively activated in cancer cells, by in situ generation of dsRNA following introduction of antisense RNA complementary to an RNA expressed specifically in the cancer cell....

متن کامل

Regulation of PKR and IRF-1 during hepatitis C virus RNA replication.

The virus-host interactions that influence hepatitis C virus (HCV) replication are largely unknown but are thought to involve those that disrupt components of the innate intracellular antiviral response. Here we examined cellular antiviral pathways that are triggered during HCV RNA replication. We report that (i) RNA replication of HCV subgenomic replicons stimulated double-stranded RNA (dsRNA)...

متن کامل

منابع من

با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


عنوان ژورنال

دوره Volume 3  شماره Supplement 1

صفحات  16- 16

تاریخ انتشار 2010-11-20

با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.

کلمات کلیدی

میزبانی شده توسط پلتفرم ابری doprax.com

copyright © 2015-2023