Poxviruses Flashcards
Briefly discuss the structure and genome type of poxviruses.
(a) What is one thing about poxviruses that makes them unique from other viruses of the same type of genome?
(b) Regarding the fact mentioned in part (a), what makes Poxviruses able to do this?
(a) Unlike many other DNA viruses, poxviruses replicate entirely within the cytoplasm of the host cell.
(b) Poxviruses replicate in the cytoplasm because** they carry all the necessary enzymes for DNA replication and transcription within their virions**.
Give examples of Poxviruses.
(1) Small pox [eradicated]
(2) Mpox
(3) Molluscum contagiosum
How are Poxviruses transmitted?
inhalation or contact with infected animals, humans or contaminated fomites [inanimate objects or surfaces that have been exposed to infectious agents]
What mechanisms do Poxviruses use to penetrate host cells?
✅ Membrane fusion: The viral envelope fuses directly with the host cell membrane, allowing the viral core to enter the cytoplasm.
✅ Macropinocytosis: The virus induces the host cell to engulf it in a large vesicle, which then releases the viral core into the cytoplasm.
Discuss Poxvirus replication.
[Poxvirus replication can be said to have three phases: an early, intermediate and late phase.]
🦠 Once inside the host cell, the virus begins the early phase of replication. During this phase, early genes are transcribed by the viral RNA polymerase. These early genes encode proteins that:
(a) promote viral replication: These proteins help in uncoating the viral DNA and intitiating DNA replication.
(b) modulate the host immune response: Some early proteins host antiviral defenses allowing the virus to replicate more efficiently.
🦠 The intermediate phase follows the early phase and involves the transcription of intermediate genes. These genes encode enzymes that replicate the viral DNA and other proteins necessary for DNA replication.
🦠 In the late phase, late genes are transcribed, leading to the production of structural proteins and enzymes required for assembling new virions.
Outline three mechanisms involved in Poxvirus exit.
(1) Lysis: The host cell is lysed, releasing the new virions into the extracellular environment.
(2) Exocytosis [budding]: Virions are transported to the cell membrane in vesicles and released by exocytosis.
(3) Extrusion (Actin Tail Assembly): Some poxviruses use actin tails to propel themselves out of the host cell, facilitating the spread to neighbouring cells.
Mpox
(a) Genus
(b) Reservoir host
(c) Geographic distribution
(a) Orthopoxvirus
(b) rodents
(c) Endemic in Central and West Africa
Name the two Mpox clades.
(1) Central African/Congo Basin Clade
(2) West African Clade
Discuss the pathogenesis of Mpox through the oropharyngeal route.
🦠 When the Mpox virus enters the body through the oropharyngeal route, it typically does so via respiratory droplets or direct contact with contaminated fluids.
🦠 The virus enters the oropharyngeal mucosa where it replicates locally. This initial replication occurs in the epithelial cells and macrophages of the mucous membranes.
🦠 Following primary replication, the virus spreads to the regional lymph nodes. This spread is mediated by infected dendritic cells and macrophages that transport the virus form the oropharyngeal mucosa to the lymphatic system.
🦠 The virus then enters the bloodstream, leading to a primary viremia.
🦠 The primary viremia allows the virus to disseminate throughout the body, reaching distant organs such as the spleen, liver and lungs. The virus can also infect the skin, leading to the characteristic rash and lesions associated with Mpox.
🦠 The virus causes extensive cell damage through direct lysis and immune modulation.
🦠 The elicited immune response may result in excessive release of cytokines [cytokine storm] can cause widespread inflammation and tissue damage.
List immune evasion mechanisms used by Mpox viruses.
(1) Reduction of cellular activation: The Mpox virus reduces the activation of immune cells, thereby dampening the overall immune response and allowing the virus to replicate more freely.
(2) Preventing IFN alpha/beta signalling: The virus inhibits interferon alpha and beta signaling pathways, which are crucial for antiviral defense, thus preventing the activation of antiviral states in infected and neighboring cells.
(3) Targeting Cytokines and Chemokines: Mpox virus produces viral proteins that mimic or bind to host cytokines and chemokines, disrupting their signaling and reducing the recruitment and activation of immune cells.
(4) Blocking activation of complement cascade: The virus produces proteins that inhibit the complement cascade, a part of the immune system that helps clear pathogens, thereby avoiding destruction by this pathway.
(5) Escaping apoptosis: The virus interferes with the host cell’s apoptotic pathways, preventing programmed cell death and allowing infected cells to survive longer and produce more virus.
(6) Preventing NF-kB activation: By inhibiting the NF-kB [Nuclear Factor kappa-light-chain-enhancer of activated B cells] pathway, the virus reduces the production of pro-inflammatory cytokines and other immune responses that would normally help control the infection.
(7) Blocking of PRR signalling cascade: The virus blocks pattern recognition receptor (PRR) signaling, which is essential for detecting viral components and initiating immune responses, thus evading early detection by the host immune system.
(8) Blocking IRF 3 signalling: The virus inhibits interferon regulatory factor 3 (IRF3) signaling, which is critical for the production of type I interferons and other antiviral responses, thereby impairing the host’s ability to mount an effective antiviral defense.
[Diagram]
What is the incubation period for Mpox?
5 - 21 days
Briefly discuss the clinical presentation of Mpox.
🦠 fever
🦠 headache
🦠 muscle pain [myalgia]
🦠 respiratory symtpoms: sorethroat, cough, shortness of breath
🦠 lymphadenopathy (esp. cervical or inguinal)
🦠 rash (local +/- spread across the body)
🦠 pain & loss of function at lesion site
Outline the Mpox rash progression.
Macules → Papules → Vesicles → Pustules → Scabs
[Diagram 1] [Diagram 2] [Diagram 3]
Further notes:
(1) Macules: the rash begins as flat, round, pink spots on the skin. They typically last 1-2 days.
(2) Papules: Macules evolve into raised bumps known as papules. This stage typically lasts for 1-2 days.
(3) Vesicles: The papules fill with clear fluid, becoming vesicles; typically lasts 1-2 days.
(4) Pustules: The vesicles then turn into pustules, which are filled with opaque pus. These pustules enlarge, become firmer, and may develop a small central depression. This stage can last around a week.
(5) Scabs: Finally, the pustules crust over and form scabs. These scabs remain for about a week before they begin to fall off, completing the rash progression.
List some complications of Mpox.
(1) Bacterial superinfection
(2) Encephalitis
(3) Septicemia
(4) Miscarriage/Still birth
[Most deaths are due to secondary infections.]
