Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks.
Abstract: Epizootics of Venezuelan equine encephalitis (VEE) involving subtype IAB viruses occurred sporadically in South, Central and North America from 1938 to 1973. Incompletely inactivated vaccines have long been suspected as a source of the later epizootics. We tested this hypothesis by sequencing the PE2 glycoprotein precursor (1,677 nucleotides) or 26S/nonstructural protein 4 (nsP4) genome regions (4,490 nucleotides) for isolates representing most major outbreaks. Two distinct IAB genotypes were identified: 1) 1940s Peruvian strains and 2) 1938-1973 isolates from South, Central, and North America. Nucleotide sequences of these two genotypes differed by 1.1%, while the latter group showed only 0.6% sequence diversity. Early VEE virus IAB strains that were used for inactivated vaccine preparation had sequences identical to those predicted by phylogenetic analyses to be ancestors of the 1960s-1970s outbreaks. These data support the hypothesis of a vaccine origin for many VEE outbreaks. However, continuous, cryptic circulation of IAB viruses cannot be ruled out as a source of epizootic emergence.
Publication Date: 1999-08-31 PubMed ID: 10466974DOI: 10.4269/ajtmh.1999.60.441Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks that occurred from 1938 to 1973 in America. The researchers tested the theory that incompletely inactivated vaccines could be the source of these outbreaks, and their evidence supports this hypothesis, although they noted that continuous, hidden circulation of the viruses is also a possible source of the outbreaks.
Research Method
- The researchers carried out their investigation by sequencing two regions of the Venezuelan equine encephalitis (VEE) virus (subtype IAB): the PE2 glycoprotein precursor (1,677 nucleotides long) and the 26S/nonstructural protein 4 (nsP4) genome regions (4,490 nucleotides long).
- They focused on isolates that represented the majority of the major outbreaks.
Identifying Different Genotypes
- The sequencing process helped them identify two distinct IAB genotypes. The first genotype strain was from Peru in the 1940s while the second genotype included isolates from South, Central and North America from the period of 1938-1973.
- Interestingly, the nucleotide sequences of these two genotypes differed by 1.1%.
- Even within the second group, originating from various parts of America, there was a relatively small sequence diversity of just 0.6% which indicates a close relationship between them.
Findings & Conclusions
- Early VEE virus IAB strains that were used in the preparation of inactivated vaccines were found to have sequences identical to those predicted through phylogenetic analysis to be ancestors of the outbreaks in the 1960s and 70s.
- These findings lend a considerable amount of support to the initial hypothesis that the source of many VEE outbreaks could indeed be the vaccines. However, the research also highlights that other factors like the hidden and continuous circulation of IAB viruses should not be ruled out as potential sources of outbreaks.
Cite This Article
APA
Weaver SC, Pfeffer M, Marriott K, Kang W, Kinney RM.
(1999).
Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks.
Am J Trop Med Hyg, 60(3), 441-448.
https://doi.org/10.4269/ajtmh.1999.60.441 Publication
Researcher Affiliations
- Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Central America / epidemiology
- DNA Primers / chemistry
- Disease Outbreaks
- Encephalitis Virus, Venezuelan Equine / classification
- Encephalitis Virus, Venezuelan Equine / genetics
- Encephalomyelitis, Equine / epidemiology
- Encephalomyelitis, Equine / virology
- Molecular Sequence Data
- North America / epidemiology
- Phylogeny
- RNA, Viral / chemistry
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Alignment
- Sequence Analysis, DNA
- Sequence Homology, Amino Acid
- Sequence Homology, Nucleic Acid
- South America / epidemiology
- Viral Vaccines / adverse effects
Grant Funding
- AI-10984 / NIAID NIH HHS
- AI-39508 / NIAID NIH HHS
- AI-39800 / NIAID NIH HHS
Citations
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- Brault AC, Powers AM, Holmes EC, Woelk CH, Weaver SC. Positively charged amino acid substitutions in the e2 envelope glycoprotein are associated with the emergence of venezuelan equine encephalitis virus. J Virol 2002 Feb;76(4):1718-30.
- Brault AC, Powers AM, Medina G, Wang E, Kang W, Salas RA, De Siger J, Weaver SC. Potential sources of the 1995 Venezuelan equine encephalitis subtype IC epidemic. J Virol 2001 Jul;75(13):5823-32.
- Dhawan S, Pan-Ngum W, MacIntyre CR, Blacksell SD. Epidemiological indicators of accidental laboratory-origin outbreaks. Epidemiol Infect 2026 Jan 2;154:e16.
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- Rawle DJ, Hugo LE, Cox AL, Devine GJ, Suhrbier A. Generating prophylactic immunity against arboviruses in vertebrates and invertebrates. Nat Rev Immunol 2024 Sep;24(9):621-636.
- Pushko P, Lukashevich IS, Johnson DM, Tretyakova I. Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses. Viruses 2024 Mar 10;16(3).
- Tretyakova I, Tomai M, Vasilakos J, Pushko P. Live-Attenuated VEEV Vaccine Delivered by iDNA Using Microneedles Is Immunogenic in Rabbits. Front Trop Dis 2022 Mar;3.
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