Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation

Michael Anishchenko, Richard A. Bowen, Slobodan Paessler, Laura Austgen, Ivorlyne P. Greene, Scott Weaver

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.

Original languageEnglish (US)
Pages (from-to)4994-4999
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number13
DOIs
StatePublished - Mar 28 2006

Fingerprint

Encephalitis
RNA Viruses
Host Specificity
Mutation
Venezuelan Equine Encephalitis Viruses
Alphavirus
Horses
Reverse Genetics
Severe Acute Respiratory Syndrome
Dengue
Viremia
Health
Zoonoses
Mutation Rate
Human Influenza
Disease Outbreaks
Ecosystem
Virulence
Rodentia
Glycoproteins

Keywords

  • Alphavirus
  • Arbovirus
  • Equine
  • Evolution

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. / Anishchenko, Michael; Bowen, Richard A.; Paessler, Slobodan; Austgen, Laura; Greene, Ivorlyne P.; Weaver, Scott.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 13, 28.03.2006, p. 4994-4999.

Research output: Contribution to journalArticle

@article{7a79e86b990845a58e0b4514a89839ef,
title = "Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation",
abstract = "RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.",
keywords = "Alphavirus, Arbovirus, Equine, Evolution",
author = "Michael Anishchenko and Bowen, {Richard A.} and Slobodan Paessler and Laura Austgen and Greene, {Ivorlyne P.} and Scott Weaver",
year = "2006",
month = "3",
day = "28",
doi = "10.1073/pnas.0509961103",
language = "English (US)",
volume = "103",
pages = "4994--4999",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation

AU - Anishchenko, Michael

AU - Bowen, Richard A.

AU - Paessler, Slobodan

AU - Austgen, Laura

AU - Greene, Ivorlyne P.

AU - Weaver, Scott

PY - 2006/3/28

Y1 - 2006/3/28

N2 - RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.

AB - RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.

KW - Alphavirus

KW - Arbovirus

KW - Equine

KW - Evolution

UR - http://www.scopus.com/inward/record.url?scp=33645521774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645521774&partnerID=8YFLogxK

U2 - 10.1073/pnas.0509961103

DO - 10.1073/pnas.0509961103

M3 - Article

C2 - 16549790

AN - SCOPUS:33645521774

VL - 103

SP - 4994

EP - 4999

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -