A molecular genetic approach to the study of Venezuelan equine encephalitis virus pathogenesis

Virulence and viremia characteristics of 1992 epizootic subtype IC Venezuelan equine encephalitis viruses and closely related enzootic subtype ID strains.

“…[11][12][13] An infectious cDNA clone generated from ID strain 66637 is now being used to test putative epizootic mutations predicted by genomic sequences and phylogenetic methods. 12 Unfortunately, rodent models used previously to assess VEE virus virulence and epizootic potential 21,23,[42][43][44] do not appear to be useful in predicting equine avirulence of the enzootic Venezuelan subtype ID strains that we tested. Guinea pigs have been shown to respond differently to some enzootic VEE virus strains than to epizootic serotypes, but this pattern does not always extend to the ID subtype.…”

“…44 Our results support this previous conclusion. Mice, which have been useful models for laboratory attenuation studies, [21][22][23] do not appear to be predictors of natural equine virulence. Although several in vitro markers including plaque size on Vero cells overlaid with unpurified agar, 12,25 hydroxylapatite chromatography elution profiles, 45 and interferon ␣/␤ sensitivity 46,47 are useful in predicting the epizootic phenotype, experimental infections of equines will continue to be required in the definitive assessment of epizootic potential.…”

“…All of these results are consistent with those of previous murine studies using epizootic VEE virus strains. [20][21][22][23] Guinea pigs also had uniformly fatal infections (Table 3); although they displayed some variability in survival time and viremia, there was again no consistent difference in response to the enzootic versus epizootic VEE virus strains. In contrast to mice and guinea pigs, female cotton rats had relatively high viremia titers, but did not show any clinical signs of infection, and all survived for 14 days (Table 3).…”

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

“…Indeed, mice lacking caspase-3 displayed tissue, placenta, and amniotic fluid of newborns with microcephaly and in the stillborn infants of women infected by Zika during pregnancy [28]. The envelope protein of encephalitic arboviruses is the major determinant of neurotropism and neurovirulence, owing to its role in receptor binding and virus entry [177][178][179]. However, sequence analysis of virulent and attenuated strains of these viruses revealed that other regions of the viral genome, including the 3´ untranslated region and nonstructural proteins, also contribute to neurovirulence and viral tropism [180].…”

Status and challenges of filovirus vaccines

“…Because VEE virus has a positive-sense RNA genome, full-length cDNA clones of VEE virus can be used to generate RNA transcripts that, when introduced into susceptible cells, will initiate a complete viral replication cycle and generate infectious virus [83]. Genes of interest such as the GP1-GP2 of MARV replace the VEE virus structural protein gene region in a cDNA plasmid of the VEE viral genome; an RNA transcript from such a plasmid, when introduced into cells, will then replicate and express the heterologous genes.…”