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Article: Biological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated

TitleBiological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated
Authors
Issue Date2005
PublisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm
Citation
World Journal of Gastroenterology, 2005, v. 11 n. 30, p. 4703-4708 How to Cite?
AbstractAIM: To investigate the biological impacts of “hot-spot” mutations on genotype B and C HBV X proteins (HBx). METHODS: Five types of “hot-spot” mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants’ expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test. RESULTS: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences. CONCLUSION: “Hot-spot” mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most “hot-spot” mutations on HBx are genotype B and C differentiated.
Persistent Identifierhttp://hdl.handle.net/10722/224614
ISSN
2015 Impact Factor: 2.787
2015 SCImago Journal Rankings: 1.076
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLin, X-
dc.contributor.authorXu, X-
dc.contributor.authorHuang, QL-
dc.contributor.authorLiu, YQ-
dc.contributor.authorZheng, DL-
dc.contributor.authorChen, WN-
dc.contributor.authorLin, JY-
dc.date.accessioned2016-04-11T07:54:21Z-
dc.date.available2016-04-11T07:54:21Z-
dc.date.issued2005-
dc.identifier.citationWorld Journal of Gastroenterology, 2005, v. 11 n. 30, p. 4703-4708-
dc.identifier.issn1007-9327-
dc.identifier.urihttp://hdl.handle.net/10722/224614-
dc.description.abstractAIM: To investigate the biological impacts of “hot-spot” mutations on genotype B and C HBV X proteins (HBx). METHODS: Five types of “hot-spot” mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants’ expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test. RESULTS: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences. CONCLUSION: “Hot-spot” mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most “hot-spot” mutations on HBx are genotype B and C differentiated.-
dc.languageeng-
dc.publisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm-
dc.relation.ispartofWorld Journal of Gastroenterology-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshDNA, Viral - genetics-
dc.subject.meshHepatitis B virus - genetics - pathogenicity-
dc.subject.meshRecombinant Proteins - genetics-
dc.subject.meshTrans-Activators - genetics-
dc.subject.meshTranscriptional Activation-
dc.titleBiological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated-
dc.typeArticle-
dc.identifier.emailLiu, YQ: ayliu@hkucc.hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3748/wjg.v11.i30.4703-
dc.identifier.pmid16094714-
dc.identifier.pmcidPMC4615415-
dc.identifier.hkuros104437-
dc.identifier.volume11-
dc.identifier.issue30-
dc.identifier.spage4703-
dc.identifier.epage4708-
dc.publisher.placeUnited States-

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