GARDNER, Christina L, Jozef HRITZ, Chengqun SUN, Dana L. VANLANDINGHAM, Timothy Y. SONG, Elodie GHEDIN, Stephen HIGGS, William B. KLIMSTRA a Kate D. RYMAN. Deliberate Attenuation of Chikungunya Virus by Adaptation to Heparan Sulfate-Dependent Infectivity: A Model for Rational Arboviral Vaccine Design. PLOS Neglected Tropical Diseases. San Francisco: PUBLIC LIBRARY SCIENCE, 2014, roč. 8, č. 2, s. "nestránkováno", 16 s. ISSN 1935-2735. doi:10.1371/journal.pntd.0002719.
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Základní údaje
Originální název Deliberate Attenuation of Chikungunya Virus by Adaptation to Heparan Sulfate-Dependent Infectivity: A Model for Rational Arboviral Vaccine Design
Autoři GARDNER, Christina L (840 Spojené státy), Jozef HRITZ (703 Slovensko, garant, domácí), Chengqun SUN (840 Spojené státy), Dana L. VANLANDINGHAM (840 Spojené státy), Timothy Y. SONG (840 Spojené státy), Elodie GHEDIN (840 Spojené státy), Stephen HIGGS (840 Spojené státy), William B. KLIMSTRA (840 Spojené státy) a Kate D. RYMAN (840 Spojené státy).
Vydání PLOS Neglected Tropical Diseases, San Francisco, PUBLIC LIBRARY SCIENCE, 2014, 1935-2735.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30000 3. Medical and Health Sciences
Stát vydavatele Spojené státy
Utajení není předmětem státního či obchodního tajemství
Impakt faktor Impact factor: 4.446
Kód RIV RIV/00216224:14740/14:00075086
Organizační jednotka Středoevropský technologický institut
UT WoS 000332017500001
Štítky kontrola MP, ok, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Martina Prášilová, učo 342282. Změněno: 17. 10. 2014 12:44.
Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine candidates is of critical importance. Historically, live-attenuated vaccines (LAVs) for protection against arthropod-borne viruses have been created by blind cell culture passage leading to attenuation of disease, while maintaining immunogenicity. Attenuation may occur via multiple mechanisms. However, all examined arbovirus LAVs have in common the acquisition of positively charged amino acid substitutions in cell-surface attachment proteins that render virus infection partially dependent upon heparan sulfate (HS), a ubiquitously expressed sulfated polysaccharide, and appear to attenuate by retarding dissemination of virus particles in vivo. We previously reported that, like other wild-type Old World alphaviruses, CHIKV strain, La Réunion, (CHIKV-LR), does not depend upon HS for infectivity. To deliberately identify CHIKV attachment protein mutations that could be combined with other attenuating processes in a LAV candidate, we passaged CHIKV-LR on evolutionarily divergent cell-types. A panel of single amino acid substitutions was identified in the E2 glycoprotein of passaged virus populations that were predicted to increase electrostatic potential. Each of these substitutions was made in the CHIKV-LR cDNA clone and comparisons of the mutant viruses revealed surface exposure of the mutated residue on the spike and sensitivity to competition with the HS analog, heparin, to be primary correlates of attenuation in vivo. Furthermore, we have identified a mutation at E2 position 79 as a promising candidate for inclusion in a CHIKV LAV.
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