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Mosquito-borne Alphaviruses

Introduction

The genus Alphavirus in the family Togaviridae contains approximately 30 members. Alphaviral encephalitides comprise three groups of viruses, genus Alphavirus: the eastern (EEEV), western (WEEV), and Venezuelan equine encephalitis viruses (VEEV). In nature, these viruses are transmitted to mammals and birds by mosquitoes.

Alphaviruses are small, relatively simple, enveloped, message-sense RNA viruses. The genome codes for structural proteins are composed of the capsid proteins (C), envelope glycoproteins (E1, E2, E3, and 6K), and non-structural proteins (nsP1, nsP2, nsP3, and nsP4).

Alphavirus genome organization and molecular structure of the virion. Fig.1 Alphavirus genome organization and molecular structure of the virion. (Holmes, 2020)

Pathogenesis

  • Alphaviruses enter the body via mosquito bites and replicate in various tissues
  • Following peripheral infection, the virus produces a transient viremia, largely through multiplication in muscle. It then crosses the blood-brain barrier and multiplies in the central nervous system (CNS).
  • Neurons are the primary target cells of encephalitic alphaviruses and alphaviruses can be directly cytolytic, and directly induce cell killing.
  • Loss of neurons, perivascular cuffing, microglial proliferation, vasculitis, and focal inflammatory infiltration are the most typical findings of human encephalitis.

Epidemiology

  • VEEV, EEEV, and WEEV typically circulate between mosquitoes and passerine birds in the wild.
  • Alphaviruses (encephalitides) are geographically restricted in distribution. They are found in North, Central, and South America.
  • In Latin America, EEEV is associated with little human disease, probably due to inherently reduced virulence compared to North American strains.
  • While most people infected with WEEV remain asymptomatic, EEE carries a substantial death rate.

Geographic range of cases of human disease induced by alphaviruses. Fig.2 Geographic range of cases of human disease induced by alphaviruses. (Baxter, 2020)

Symptoms

Clinical disease syndromes induced by natural alphavirus infection are associated with many symptoms and neurologic diseases.

  • Fever
  • Headache
  • Stupor or coma
  • Seizures
  • Encephalitis (brain inflammation)
  • Myelitis (spinal cord inflammation)
  • Meningitis (inflammation of the meninges)
  • Radiculitis (inflammation of the spinal nerve roots)

Table.1 Disease of pathogenic alphaviruses.

Associated alphaviruses Confirmed or putative mosquito vector(s) species Confirmed or putative reservoir host(s) Disease manifestations
New world alphaviruses EEEV Culiseta melanura, Culex erraticus Passeriformes birds Encephalitic disease includes headache, vomiting, diarrhea, seizures, and coma.
VEEV Culex (Melanoconion) spp. Small mammals Similar to EEEV; infection has a lower mortality rate than EEEV.
WEEV Culex tarsalis Wild birds Mainly subclinical or nonspecific febrile illness; can progress to encephalitis in rare cases.
Old World alphaviruses Chikungunya (CHIKV) Aedes albopictus, Aedes aegypti, Aedes (subgenus Stegomyia) Nonhuman primates Fever, polyarthralgia (frequently becomes recurrent), myalgia, rash, and headache, neurologic diseases (atypical disease manifestation).

Prevention and Treatment

There is no specific treatment or established cure for alphaviruses. Treatment of VEE, EEE, and WEE is limited to supportive therapies to maintain fluid balance and prevent intracranial pressure. Although EEEV, VEEV, and WEEV vaccines have been administered to persons at risk by the U.S. Army under IND protocols since the 1960s, currently, there are no licensed treatments or vaccines available for these viruses in humans.

What Can We offer

Creative Biolabs provides a comprehensive suite of virology antibody discovery and development services. Based on our advanced platforms, we can offer custom antibodies targeting EEEV, VEEV, and WEEV, to help our customers achieve their virology research goals. In addition, our services include ViroAntibody neutralization, discovery, engineering, customized. Please feel free to contact us for further information.

References

  1. Holmes, A.C.; et al. A molecular understanding of alphavirus entry. PLoS Pathog. 2020, 16(10): e1008876.
  2. Baxter, V.K.; Heise, M.T. Immunopathogenesis of alphaviruses. Adv Virus Res. 2020, 107: 315-382.

All products and services are intended for Research Use Only, and NOT to be used in diagnostic or therapeutic procedures.

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