Matches in SemOpenAlex for { <https://semopenalex.org/work/W2163551436> ?p ?o ?g. }
- W2163551436 endingPage "6626" @default.
- W2163551436 startingPage "6615" @default.
- W2163551436 abstract "ABSTRACT The human cytomegalovirus (HCMV) immediate-early 2 (IE2) protein is a multifunctional factor essential for viral replication. IE2 modulates both viral and host gene expression, deregulates cell cycle progression, acts as an immunomodulator, and antagonizes cellular antiviral responses. Based on these facts, IE2 has been proposed as an important target for the development of innovative antiviral approaches. We previously identified the 6-aminoquinolone WC5 as a promising inhibitor of HCMV replication, and here, we report the dissection of its mechanism of action against the viral IE2 protein. Using glutathione S -transferase (GST) pulldown assays, mutagenesis, cell-based assays, and electrophoretic mobility shift assays, we demonstrated that WC5 does not interfere with IE2 dimerization, its interaction with TATA-binding protein (TBP), and the expression of a set of cellular genes that are stimulated by IE2. On the contrary, WC5 targets the regulatory activity exerted by IE2 on different responsive viral promoters. Indeed, WC5 blocked the IE2-dependent negative regulation of the major immediate-early promoter by preventing IE2 binding to the crs element. Moreover, WC5 reduced the IE2-dependent transactivation of a series of indicator constructs driven by different portions of the early UL54 gene promoter, and it also inhibited the transactivation of the murine CMV early E1 promoter by the IE3 protein, the murine cytomegalovirus (MCMV) IE2 homolog. In conclusion, our results indicate that the overall anti-HCMV activity of WC5 depends on its ability to specifically interfere with the IE2-dependent regulation of viral promoters. Importantly, our results suggest that this mechanism is conserved in murine CMV, thus paving the way for further preclinical evaluation in an animal model." @default.
- W2163551436 created "2016-06-24" @default.
- W2163551436 creator A5006328333 @default.
- W2163551436 creator A5008294104 @default.
- W2163551436 creator A5010835490 @default.
- W2163551436 creator A5027412291 @default.
- W2163551436 creator A5029436365 @default.
- W2163551436 creator A5054053277 @default.
- W2163551436 creator A5058157645 @default.
- W2163551436 creator A5062786874 @default.
- W2163551436 creator A5091348755 @default.
- W2163551436 date "2014-11-01" @default.
- W2163551436 modified "2023-10-16" @default.
- W2163551436 title "The 6-Aminoquinolone WC5 Inhibits Different Functions of the Immediate-Early 2 (IE2) Protein of Human Cytomegalovirus That Are Essential for Viral Replication" @default.
- W2163551436 cites W1480536342 @default.
- W2163551436 cites W1582479873 @default.
- W2163551436 cites W1606747831 @default.
- W2163551436 cites W1685950740 @default.
- W2163551436 cites W1754219621 @default.
- W2163551436 cites W1763782658 @default.
- W2163551436 cites W1797852794 @default.
- W2163551436 cites W1849236811 @default.
- W2163551436 cites W194432110 @default.
- W2163551436 cites W1947794291 @default.
- W2163551436 cites W1958288590 @default.
- W2163551436 cites W1970250038 @default.
- W2163551436 cites W1971876556 @default.
- W2163551436 cites W1986052682 @default.
- W2163551436 cites W2004602223 @default.
- W2163551436 cites W2012427126 @default.
- W2163551436 cites W2019517008 @default.
- W2163551436 cites W2035829105 @default.
- W2163551436 cites W2036455733 @default.
- W2163551436 cites W2040624923 @default.
- W2163551436 cites W2044130411 @default.
- W2163551436 cites W2049693838 @default.
- W2163551436 cites W2053613554 @default.
- W2163551436 cites W2060781532 @default.
- W2163551436 cites W2065045640 @default.
- W2163551436 cites W2065447003 @default.
- W2163551436 cites W2073207414 @default.
- W2163551436 cites W2073558615 @default.
- W2163551436 cites W2074012862 @default.
- W2163551436 cites W2074620410 @default.
- W2163551436 cites W2076613886 @default.
- W2163551436 cites W2082607586 @default.
- W2163551436 cites W2083771792 @default.
- W2163551436 cites W2088475360 @default.
- W2163551436 cites W2089171980 @default.
- W2163551436 cites W2089718689 @default.
- W2163551436 cites W2096560689 @default.
- W2163551436 cites W2097413546 @default.
- W2163551436 cites W2104095249 @default.
- W2163551436 cites W2105910325 @default.
- W2163551436 cites W2107130718 @default.
- W2163551436 cites W2113444803 @default.
- W2163551436 cites W2115518922 @default.
- W2163551436 cites W2116161740 @default.
- W2163551436 cites W2117179585 @default.
- W2163551436 cites W2117505476 @default.
- W2163551436 cites W2120948500 @default.
- W2163551436 cites W2131928677 @default.
- W2163551436 cites W2142161841 @default.
- W2163551436 cites W2145768518 @default.
- W2163551436 cites W2147426050 @default.
- W2163551436 cites W2147611204 @default.
- W2163551436 cites W2150249444 @default.
- W2163551436 cites W2156172405 @default.
- W2163551436 cites W2164065256 @default.
- W2163551436 cites W2164557026 @default.
- W2163551436 cites W2164731692 @default.
- W2163551436 cites W2165550496 @default.
- W2163551436 cites W2167623438 @default.
- W2163551436 cites W2218221865 @default.
- W2163551436 cites W2409275573 @default.
- W2163551436 cites W2950275691 @default.
- W2163551436 cites W4248272730 @default.
- W2163551436 cites W988054948 @default.
- W2163551436 doi "https://doi.org/10.1128/aac.03309-14" @default.
- W2163551436 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4249379" @default.
- W2163551436 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25155603" @default.
- W2163551436 hasPublicationYear "2014" @default.
- W2163551436 type Work @default.
- W2163551436 sameAs 2163551436 @default.
- W2163551436 citedByCount "14" @default.
- W2163551436 countsByYear W21635514362016 @default.
- W2163551436 countsByYear W21635514362017 @default.
- W2163551436 countsByYear W21635514362018 @default.
- W2163551436 countsByYear W21635514362019 @default.
- W2163551436 countsByYear W21635514362020 @default.
- W2163551436 countsByYear W21635514362021 @default.
- W2163551436 countsByYear W21635514362022 @default.
- W2163551436 countsByYear W21635514362023 @default.
- W2163551436 crossrefType "journal-article" @default.
- W2163551436 hasAuthorship W2163551436A5006328333 @default.
- W2163551436 hasAuthorship W2163551436A5008294104 @default.
- W2163551436 hasAuthorship W2163551436A5010835490 @default.
- W2163551436 hasAuthorship W2163551436A5027412291 @default.