Virology Ch. 16 Filoviruses

Filoviruses Overview

  • Filoviruses are a family of viruses that include the genera Marburgvirus and Ebolavirus.
  • Named for their filamentous structure; Filoviridae from Latin filum meaning thread.

Viruses and Hosts

  • Filoviridae consists of two genera:
    • Marburgvirus: Single species
    • Ebolavirus: Multiple species named after their discovery sites:
    • Bundibugyo
    • Cote d’Ivoire
    • Reston
    • Sudan
    • Zaire
  • Likely transmitted from fruit bats to primates.

Virion Structure

  • Filamentous envelope particles:
    • Diameter: 80 nm
    • Length: 800 nm or more
  • Contains helically arranged nucleocapsids.

Genome Characteristics

  • Genome Composition:
    • Linear single-stranded RNA (ssRNA), negative sense
    • Size: 19 kb
  • Contains seven genes, transcribed from the 3' end by viral RNA polymerase (RNA pol).
  • Each gene generally produces a single mRNA and a single protein, flanked by conserved sequences for transcription termination and polyadenylation.

Virion Composition

  • Major proteins packaged in the virion include:
    • Nucleocapsid Protein (NP)
    • RNA Polymerase Cofactor (VP35)
    • Matrix Protein (VP40)
    • Envelope Glycoproteins (GP, cleaved into GP1 and GP2)
    • Minor Nucleocapsid Protein (VP30)
    • Membrane Protein (VP24)
    • RNA Polymerase (L)
  • Ebola virus also produces additional glycoproteins: secreted glycoproteins (sGP, delta-peptide).

Distinctive Characteristics

Transcription and Replication
  • The negative sense RNA genome serves as a template for:
    • mRNA synthesis
    • Genome replication
  • Inclusion bodies containing viral nucleocapsids can be observed in the cytoplasm of infected cells.
Glycoprotein Function
  • The glycoprotein facilitates:
    • Receptor binding
    • Entry via fusion with host cells.
  • Multiple cellular receptors are involved in binding:
    • Asialoglycoprotein receptor
    • Folate receptor-α
    • Integrins
    • DC-SIGN
  • Virus can enter clathrin-coated pits and fuse within vesicles.
RNA Editing
  • Ebola virus employs RNA editing to produce two glycoproteins from one gene:
    • A shorter form is secreted, lacking the transmembrane domain.
    • RNA polymerase "stutters" to add an extra A residue affecting the reading frame.

Diseases and Pathogenesis

  • Infections with Marburg and Ebola viruses lead to severe hemorrhagic fever, characterized by:
    • Fever
    • Hemorrhaging
    • Liver dysfunction
    • Intravascular coagulation
    • Shock
  • Lethality rate can reach 90% in outbreaks.
  • Disease is followed by lengthy periods of absence.
Historical Outbreaks
  • Marburg virus outbreak first noted in Germany in 1967.
  • Ebola virus outbreaks began in Zaire and Sudan in 1976.
  • Reston ebolavirus is an exception, not linked to human fatalities.
2014-2016 Ebola Outbreak
  • Initial case traced to a child in Guinea, virus spread rapidly,
    • Over 28,000 confirmed cases and 11,325 deaths recorded in affected regions.

Disease Mechanisms

  • Pathogenesis involves:
    • Lesions on internal organs
    • Gastrointestinal tract hemorrhage
    • Disseminated intravascular coagulation
    • Platelet abnormalities
    • Cytokine release elevates vascular permeability leading to shock.
  • Clinical features:
    • Sudden fever, chills, headaches, muscle pain followed by nausea, vomiting, distinct rash, and bleeding.

Diagnosis and Treatment

  • Diagnosis: Focuses on:
    • Host-specific immune response
    • Viral particle detection.
  • Treatment: Primarily symptomatic and supportive care.
  • Vaccines: rVSV-ZEBOV (December 2019), cAd3-EBOZ (Do note clinical trials).

Fundamental Concepts

  • Filoviruses belong to the family Filoviridae, closely related to paramyxoviruses and rhabdoviruses.

  • Cause sporadic severe hemorrhagic fevers predominantly in Central Africa.

  • Human-to-human transmission is inefficient and primarily occurs with close contact.

  • Reservoirs are likely fruit bats.

  • Filovirus genomes consist of seven genes, allowing for the incorporation of multiple proteins into newly formed virions.

  • RNA editing enables production of functionally distinct proteins from a single gene, enhancing viral adaptability.

  • Research on infectious filoviruses is conducted in high containment laboratories due to their pathogenic nature.