Specific Restrictions in the Progression of Venezuelan Equine Encephalitis Virus-Induced Disease Resulting from Single Amino Acid Changes in the Glycoproteins

摘要: Abstract The pathogenesis of Venezuelan equine encephalitis virus (VEE) was examined in the mouse model using V3000, a derived from molecular clone Trinidad donkey strain VEE. These results were compared parallel experiments with avirulent mutants VEE by site-directed mutagenesis clone. Adult mice, inoculated subcutaneously their left rear footpad followed time course study for 6 days which 15 organs tested histopathological changes, presence viral antigen immunohistochemical staining, nucleic acid situ hybridization analysis, and content viable virus. Virus detected inoculation site, but until 12 hr postinoculation (pi), level did not suggest early replication. By 4 pi, however, replication V3000 evident draining popliteal lymph node. At this point, no could be isolated any other organ examined. hr, significant serum viremia observed, at low number well vascularized organs, including spleen, heart, lung, liver, kidney, adrenal gland. 18 high titers present all lymphoid examined, these tissues appeared to major peripheral sites cleared 3-4 pi. In second phase infection, invaded central nervous system (CNS), replicated predominantly neurons, persisted brain death encephalitis. Pathologic findings as immunocytochemical examination generally coordinate titration. A mutant V3010, contained mutation gene E2 glycoprotein codon 76 (Glu Lys) rendered it after inoculation. Detection V3010 node sporadic sometimes delayed long 3 Infrequent and/or spread also observed. Analogous performed route: V3014, differing three loci (E2 Lys 209, E1 Thr 272, Asn 239), single-site V3032 209) V3034 (E1 272). mutations V3014 prevented beyond 209 allowed without or invasion CNS, 272 characterized near normal replication, only CNS. that VEE-induced disease sequence events can defined interdicting pathogenic pathway specific genome.