Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-2 (of 2 Records) |
Query Trace: White DM[original query] |
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The major determinant of attenuation in mice of the Candid1 vaccine for Argentine hemorrhagic fever is located in the G2 glycoprotein transmembrane domain
Albarino CG , Bird BH , Chakrabarti AK , Dodd KA , Flint M , Bergeron E , White DM , Nichol ST . J Virol 2011 85 (19) 10404-8 Candid1, a live-attenuated Junin virus vaccine strain, was developed during the early 1980s to control Argentine hemorrhagic fever, a severe and frequently fatal human disease. Six amino acid substitutions were found to be unique to this vaccine strain, and their role in virulence attenuation in mice was analyzed using a series of recombinant viruses. Our results indicate that Candid1 is attenuated in mice through a single amino acid substitution in the transmembrane domain of the G2 glycoprotein. This work provides insight into the molecular mechanisms of attenuation of the only arenavirus vaccine currently available. |
Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains.
Albarino CG , Bird BH , Chakrabarti AK , Dodd KA , White DM , Bergeron E , Shrivastava-Ranjan P , Nichol ST . J Virol 2010 85 (1) 112-22 The Arenaviridae are a diverse and globally distributed collection of viruses that are primarily maintained by rodent reservoirs. Junin virus (JUNV) and Lassa virus (LASV) can both cause significant outbreaks of severe and often fatal human disease throughout their respective endemic areas. In an effort to improve upon the existing live attenuated JUNV Candid 1 vaccine, we generated a genetically homogenous stock of this virus from cDNA copies of the virus S and L segments using a reverse genetics system. Further, these cDNAs were used in combination with LASV cDNAs to successfully generate two recombinant Candid1 JUNV/LASV chimeric viruses (via GPC envelope exchange). It was found that while the GPC extra-virion domains were readily exchangeable, homologous stable signal peptide (SSP) and G2 transmembrane and cytoplasmic tail domains were essential for correct GPC maturation and production of infectious chimeric viruses. The switching of the JUNV and LASV G1/G2 ectodomains within the Candid1 vaccine background did not alter the attenuated phenotype of the vaccine strain in a lethal mouse model. These recombinant chimeric viruses shed light on the fundamental requirements of arenavirus GPC maturation and may serve as a strategy for the development of bivalent JUNV and LASV vaccine candidates. |
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