Poxviruses Flashcards

Overview of Poxviruses

• Poxviruses are a family of large DNA viruses that include several medically significant pathogens.

• Two main subfamilies:

  • Chordopoxvirinae: Infect vertebrates; consists of 18 genera including those of medical importance.

  • Entomopoxvirinae: Infect invertebrates; contains 4 genera.

Structure of Poxviruses

• Virion Characteristics:

  • Oval or brick-shaped, measuring 200-400 nm in length, visible with powerful light microscopes.

  • External surface is ridged, arranged in rows or helically.

  • Composed of over 100 virus-encoded proteins.

  • Resilient to environmental degradation.

• Outer Structure:

  • Made of lipids and proteins, surrounding a biconcave core composed of tightly compressed nucleoprotein and lateral bodies.

• Mature Forms:

  • Extracellular Enveloped Virions (EEV): Contain two membranes.

  • Intracellular Mature Virions (IMV): Have only an inner membrane.

Genome Structure and Replication

• Genome:

  • Linear double-stranded DNA (dsDNA) ranging from 130-375 kb with ~200 genes.

  • Flanked by inverted terminal repeat (ITR) sequences, covalently closed.

• Replication Cycle:

  • Attachment and Entry:

    • Virus attaches to cell surface receptors, with a complex required for membrane fusion and core entry.

  • Gene expression involves three phases:

    • Early phase: Virus-specific genes expressed in cytoplasm shortly after infection, crucial for immune evasion.

    • Intermediate phase: Triggered by early proteins, leading to genomic replication.

    • Late phase: Structural proteins and enzymes produced, ranging from 140 min to 48 hours post-infection.

Translation and Assembly

• Translation:

  • Viral mRNAs produced without introns; require virus-encoded capping enzymes for stability.

  • Translation initiation is less reliant on host cell machinery, due to the viral mRNA structure.

• Assembly Process:

  • Initial assembly forms an immature virion, which matures into a brick-shaped intracellular mature virion (IMV).

  • IMVs may acquire an additional membrane via the Golgi apparatus.

  • Actin tails promote direct transfer of assembled virions to surrounding cells.

Immune Evasion Strategies

• Poxviruses produce "viroceptors" (secreted cellular receptors) and "virokines" (ligands that act on host receptors) to modulate host immune response.

• Viral proteins can inhibit apoptosis and counteract antiviral effects of interferons, highlighting robust immune evasion mechanisms.

Medical Perspectives on Poxviruses

• Smallpox: Caused by Variola virus (two forms: major and minor); characterized by high mortality rates.

  • Eradication achieved through vaccination, particularly using Vaccinia virus (VACV).

  • Last natural outbreak in 1977.

• Monkeypox (Mpox): Related to smallpox, but with a lower mortality rate; zoonotic transmission and outbreaks primarily in Africa.

  • Recent global concerns have led to renewed focus on prevention and control strategies.

• Poxvirus Treatments:

  • Development of antivirals like Tecovirimat for use against orthopoxviruses, including potential treatment for smallpox and Mpox.