Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence.
Enhanced mutagenesis may result in RNA virus extinction, but the molecular events underlying this process are not well understood. Here we show that 5-fluorouracil (FU)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (LCMV) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. Furthermore, fitness recovery passages in the absence of FU, or alternate virus passages in the presence and absence of FU, led to profound differences in the capacity of LCMV to produce progeny, without modification of the consensus genomic sequence. Molecular genetic analysis failed to produce evidence of hypermutated LCMV genomes. The results suggest that low-level mutagenesis to enrich the viral population with defector, interfering genomes harboring limited numbers of mutations may mediate the loss of infectivity that accompanies viral extinction.
Grande-Pérez
Ana
A
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Gómez-Mariano
Gema
G
Lowenstein
Pedro R
PR
Domingo
Esteban
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005472:Fluorouracil / Q000494:pharmacology; D016679:Genome, Viral; D006168:Guinea Pigs; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D012367:RNA, Viral / Q000737:chemistry*
D012367:RNA, Viral; D005472:Fluorouracil