Sequence analysis of the small RNA segment of guinea pig-passaged Pichinde virus variants.
The established animal model for Lassa fever is based on the new world arenavirus Pichinde (PIC). Natural isolates of PIC virus are attenuated in guinea pigs, but serial guinea pig passage renders them extremely virulent in that host. We have compared the nucleotide sequences of the small RNA segments of two attenuated, low-passage variants of the PIC virus Munchique strain (CoAn 4763) and two virulent, high-passage derivatives. Missense mutations in the glycoprotein precursor (GPC) gene at codons GPC-119, GPC-140, and GPC-164 and the nucleoprotein gene (NP) codons NP-35 and NP-374 were most closely associated with virulence. Codon GPC-140 is predicted to represent a region of peak hydrophilicity of the glycoprotein 1 (GP1); it is conceivable that mutations at this site could influence virulence by altering B cell epitopes or virus attachment protein conformation.
Zhang
L
L
Department of Pathology and Center for Tropical Diseases, University of Texas Medical Branch, Galveston 77555-0609, USA.
Marriott
K
K
Aronson
J F
JF
D000818:Animals; D001483:Base Sequence; D003062:Codon; D014644:Genetic Variation; D006168:Guinea Pigs; D006478:Hemorrhagic Fever, American / Q000821:virology*; D007928:Lethal Dose 50; D008297:Male; D008957:Models, Genetic; D020125:Mutation, Missense; D010641:Phenotype; D018052:Pichinde virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D003062:Codon; D012313:RNA