کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8523233 1557790 2018 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Impact of RNA polymerase I inhibitor CX-5461 on viral kinase-dependent and -independent cytomegalovirus replication
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Impact of RNA polymerase I inhibitor CX-5461 on viral kinase-dependent and -independent cytomegalovirus replication
چکیده انگلیسی
Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production. Interestingly, adding CX-5461 after the onset of viral DNA synthesis resulted in a greater reduction compared to continuous treatment starting early during infection. We observed an accompanying increase in cyclin-dependent kinase inhibitor p21 in infected cells treated late but not early which likely explains the differences. Our previous studies demonstrated the importance of p21 in the antiviral activity of the HCMV kinase inhibitor, maribavir. Addition of CX-5461 increased the anti-HCMV activity of maribavir. Our data demonstrate that CX-5461 inhibits HCMV replication and synergizes with maribavir to disrupt infection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 153, May 2018, Pages 33-38
نویسندگان
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