20980515
not annotated - annotated - LINNAEUS only
Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains.
The Arenaviridae are a diverse and globally distributed collection of viruses that are maintained primarily 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 areas of endemicity. In an effort to improve upon the existing live attenuated JUNV Candid1 vaccine, we generated a genetically homogenous stock of this virus from cDNA copies of the virus S and L segments by 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 envelope glycoprotein [GPC] exchange). It was found that while the GPC extravirion 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.
Ann file
T1 Species 306 317 Junin virus
N1 Reference T1 Taxonomy:11619
T2 Species 319 323 JUNV
N2 Reference T2 Taxonomy:11619
T3 Species 329 340 Lassa virus
N3 Reference T3 Taxonomy:11620
T4 Species 342 346 LASV
N4 Reference T4 Taxonomy:11620
T5 Species 411 416 human
N5 Reference T5 Taxonomy:9606
T6 Species 532 536 JUNV
N6 Reference T6 Taxonomy:11619
T7 Species 746 750 LASV
N7 Reference T7 Taxonomy:11620
T8 Species 806 810 JUNV
N8 Reference T8 Taxonomy:11619
T9 Species 811 815 LASV
N9 Reference T9 Taxonomy:11620
T10 Species 1155 1159 JUNV
N10 Reference T10 Taxonomy:11619
T11 Species 1164 1168 LASV
N11 Reference T11 Taxonomy:11620
T12 Species 1298 1303 mouse
N12 Reference T12 Taxonomy:10090
T13 Species 1478 1482 JUNV
N13 Reference T13 Taxonomy:11619
T14 Species 1487 1491 LASV
N14 Reference T14 Taxonomy:11620