Specific restrictions in the progression of Venezuelan equine encephalitis virus-induced disease resulting from single amino acid changes in the glycoproteins
- PMID: 7856110
- DOI: 10.1006/viro.1995.1022
Specific restrictions in the progression of Venezuelan equine encephalitis virus-induced disease resulting from single amino acid changes in the glycoproteins
Abstract
The pathogenesis of Venezuelan equine encephalitis virus (VEE) was examined in the mouse model using V3000, a virus derived from a molecular clone of the Trinidad donkey strain of VEE. These results were compared in parallel experiments with avirulent mutants of VEE derived by site-directed mutagenesis of the clone. Adult mice, inoculated subcutaneously in their left rear footpad with V3000, were followed in a time course study for 6 days in which 15 organs were tested for histopathological changes, for the presence of viral antigen by immunohistochemical staining, for the presence of viral nucleic acid by in situ hybridization analysis, and for content of viable virus. Virus was detected in the footpad inoculation site, but until 12 hr postinoculation (pi), the level of virus did not suggest early viral replication. By 4 hr pi, however, replication of V3000 was evident in the draining popliteal lymph node. At this early time point, no virus could be isolated from any other organ examined. At 12 hr, a significant serum viremia was observed, and virus was detected at a low level in a number of well vascularized organs, including spleen, heart, lung, liver, kidney, and adrenal gland. By 18 hr, high virus titers were present in serum and all the lymphoid organs examined, and these tissues appeared to be the major peripheral sites of V3000 replication. Virus in serum and peripheral organs was cleared by 3-4 days pi. In a second phase of the infection, V3000 invaded the central nervous system (CNS), replicated predominantly in neurons, and persisted in the brain until death by encephalitis. Pathologic findings as well as the results of immunocytochemical and in situ hybridization examination were generally coordinate with virus titration. A site-directed mutant of V3000, V3010, contained a mutation in the gene for the E2 glycoprotein at codon 76 (Glu to Lys) which rendered it avirulent after footpad inoculation. Detection of V3010 replication in the draining lymph node was sporadic and was sometimes delayed to as long as 3 days pi. Infrequent and/or delayed virus spread to other sites also was observed. Analogous experiments were performed with other mutants which were avirulent by the footpad inoculation route: V3014, a mutant differing from V3000 at three loci (E2 Lys 209, E1 Thr 272, and E2 Asn 239), as well as single-site mutants V3032 (E2 Lys 209) and V3034 (E1 Thr 272).(ABSTRACT TRUNCATED AT 400 WORDS)
Similar articles
-
A single-site mutant and revertants arising in vivo define early steps in the pathogenesis of Venezuelan equine encephalitis virus.Virology. 2000 Apr 25;270(1):111-23. doi: 10.1006/viro.2000.0241. Virology. 2000. PMID: 10772984
-
Kinetics of cytokine expression and regulation of host protection following infection with molecularly cloned Venezuelan equine encephalitis virus.Virology. 1997 Jul 7;233(2):302-12. doi: 10.1006/viro.1997.8617. Virology. 1997. PMID: 9217054
-
Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: effect of an attenuating mutation in the 5' untranslated region.J Virol. 2001 Apr;75(8):3706-18. doi: 10.1128/JVI.75.8.3706-3718.2001. J Virol. 2001. PMID: 11264360 Free PMC article.
-
Venezuelan equine encephalitis.Annu Rev Entomol. 2004;49:141-74. doi: 10.1146/annurev.ento.49.061802.123422. Annu Rev Entomol. 2004. PMID: 14651460 Review.
-
[Venezuelan equine encephalitis: state-of-the-art].Vopr Virusol. 2006 Nov-Dec;51(6):10-3. Vopr Virusol. 2006. PMID: 17214075 Review. Russian.
Cited by
-
Venezuelan equine encephalitis virus infection of spiny rats.Emerg Infect Dis. 2005 May;11(5):663-9. doi: 10.3201/eid1105.041251. Emerg Infect Dis. 2005. PMID: 15890116 Free PMC article.
-
Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles.J Virol. 2000 Jan;74(1):371-8. doi: 10.1128/jvi.74.1.371-378.2000. J Virol. 2000. PMID: 10590126 Free PMC article.
-
Individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with Lassa and Ebola viruses.J Virol. 2001 Dec;75(23):11677-85. doi: 10.1128/JVI.75.23.11677-11685.2001. J Virol. 2001. PMID: 11689649 Free PMC article.
-
High-resolution functional mapping of the venezuelan equine encephalitis virus genome by insertional mutagenesis and massively parallel sequencing.PLoS Pathog. 2010 Oct 14;6(10):e1001146. doi: 10.1371/journal.ppat.1001146. PLoS Pathog. 2010. PMID: 20976195 Free PMC article.
-
Innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated TLR7 ligand.J Innate Immun. 2014;6(3):315-24. doi: 10.1159/000355217. Epub 2013 Nov 1. J Innate Immun. 2014. PMID: 24192551 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous