Poxviruses Overview

Poxviruses

• Poxviruses are a family of viruses that infect vertebrates, including humans and other mammals, and invertebrates, including insects.
• Poxviruses are characterized by their complex, brick-shaped or ovoid particles.
• Poxvirus particles are roughly 310nm long, 240nm wide, and 140nm high
• They have a unique structure, lacking typical symmetry elements.
• The particle has an internal core and lateral bodies.
• Poxviruses exist in two forms: mature virus (MV) and enveloped virus (EV).
• The MV has a single lipid membrane while the EV has a double lipid membrane.
• Poxviridae originates from the English word "pocks", referring to skin lesions caused by the virus.
• Two subfamilies exist: Chordopoxvirinae and Entomopoxvirinae.
• Chordopoxvirinae infects vertebrates like monkeys and cattle.
• Human poxvirus infections include: smallpox (variola), vaccinia (vaccine strain for smallpox), and molluscum contagiosum.
• Molluscum contagiosum is a relatively rare but more common in immunocompromised patients.
• Entomopoxvirinae infects insects and birds, such as butterflies, flies, and moths
• The viruses are divided into several genera that infect multiple hosts, each with its own hosts.
• Smallpox was a globally debilitating and fatal disease for centuries.
• Evidence for the existence of smallpox is seen in Egyptian mummies.
• By the tenth century, smallpox had spread throughout Asia, Europe, and North Africa.
• Colonization spread smallpox globally in the 16-18th centuries.
• During the 17th century, it was common for children to be exposed to it
• Mortality rates for smallpox ranged from 1% to 40%, but in endemic areas, the average case fatality rate was 25%.
• A disease progression begins with respiratory infection, then an asymptomatic phase lasting roughly 12 days then sudden onset of fever, rash and vomiting (four days) with painful rash covering the body, blisters, difficult breathing and pain in the airways and throat( 12 days).
• Variolation was a practice of causing a less severe form of the disease through deliberate inoculation procedures creating an artificial, less-severe disease
• Variolation involved using materials from smallpox sores (pustules) to inoculate uninfected individuals.
• Inoculations were performed either by scratching material onto the arm or by nasal spray.
• Variolation was less severe than a natural infection, and it led to the development of vaccination.
• In 1796, Edward Jenner developed and published a method for vaccination using cowpox lesions as material.
• Jenner observed that milkmaids exposed to cowpox did not exhibit symptoms of smallpox.
• Jenner tested cowpox inoculation on an 8-year-old boy, and the boy remained free of smallpox symptoms post-inoculation.
• By the mid-1800s, the virus used to create smallpox vaccinations changed from cowpox to vaccinia virus
• Smallpox eradication is considered one of the major accomplishments of global public health.
• Smallpox was eradicated worldwide in 1980.
• Poxviruses remain a topic of intensive research, and vaccinia virus is used in research laboratories today
• There are very limited worldwide stocks of live vaccinia viruses due to safety concerns
• Currently there are only two worldwide sources: CDC in Atlanta, GA and VECTOR Institute in Koltsovo, Russia
• The small pox viruses are quite stable
• The poxvirus genome and proteins have linear double-stranded DNA ranging 150-250kb (vaccinia virus: 200kb).
• The poxvirus genome has closed hairpin ends and there are typically 10kb inverted terminal repeats.
• Each poxvirus gene has its own promoter for transcription.
• Virion sections reveal a biconcave core flanked by lateral bodies, these are trypsin-sensitive, and contain proteins with unknown composition and function.
• The internal core is encircled by a core wall structure
• There are tubular features present inside the core that contain the DNA
• The tubules contain viral enzymes required for the synthesis of mRNA.
• Poxviruses have two forms: mature virus (MV) and extracellular virus (EV)
• Each form differs in membrane composition resulting from differences in morphogenesis, but both forms are infectious.
• The surface proteins on the mature virus bind to cellular receptors.
• The mature virus (MV) has an outer envelope and enters host cells via fusion or endocytosis.
• The MV attaches to glycosaminoglycans which contain (broad host range) of polysaccharides, formed from repeating units different sugars including one amino sugar bound to host cell surface proteins
• The extracellular virus (EV) has a membrane that ruptures due to decreased pH in the endosome, releasing the mature virus particle, and eventually fuses with the vesicle during endocytosis releasing the virion core into the cytoplasm.
• The EVs envelope is fragile and can rupture once in contact with the host cell surface which releases the MV particle.
• Poxviruses replicate in the cytoplasm, a relatively uncommon occurrence for DNA viruses
• Virus-coded enzymes are packaged inside the core and carry out early RNA synthesis and packaging.
• The vaccinia virion can act as an mRNA synthesis machine.
• Viral DNA replication within the cytoplasm creates "DNA factories" visible using electron microscopy.
• Poxviruses produce large DNA concatemers that are later resolved into monomers.
• The poxvirus DNA duplex is linear with closed ends.
• There are host cell enzymes called helicases that can nick one end.
• There are terminal repeats that hydrogen bond to each other forming hairpin loops.
• DNA polymerase extends the 3' end
• The free 3' end folded over by the hairpin loop acts as a primer for DNA synthesis, this is called 'self-priming'.
• DNA is replicated around the other terminal loop, and two genomes are formed that are joined end to end and create a concatemer.
• Concatemers are cleaved into individual genomes.
• Ends are ligated (sealed) with formation of a covalent bond.
• Site-specific nicks are performed on one of the hairpins.
• After extension the hairpin ends are refolded.
• Entire genome length is synthesized then loops back through the second hairpin to create a head to head dimer.
• Concatemers are resolved by virus coded resolvase.
• The virus-coded resolvase creates staggered single-strand breaks at the ends of concatemers for proper genome resolution.
• Intermediate and late genes are termed postreplicative genes, transcribed after DNA replication has begun.
• Separate promoters and initiation factors are employed for initiating intermediate and late genes.
• Intermediate genes require two viral transcription factors (VITFs) and a host cell factor for mRNA metabolism
• Late gene expression requires three viral transcription factors (VLTFs) and possibly an additional early gene product along with a host-cell factor.
• The postreplicative mRNAs have poly(A) extensions and have heterogeneity in their 3' ends.
• A slippage mechanism during transcription initiation adds poly(A) tails to the mRNAs
• The assembly of vaccinia virions involves the production and synthesis of rigid crescent-shaped structures that will form the mature viral envelope that's de novo synthesis and it doesn't derive from a pre-existing internal membrane.
• Lipids are delivered to crescent-shaped structures in small vesicles from the ER.
• Crescent structures mature into spheres which are the immature virions and enclose the viroplasm.
• Viral DNA enters the spheres to form discrete cores, also called nucleoids.
• Immature virions develop internal core and lateral bodies by rearrangement.
• Matures virions capture materials inside spheres.
• The majority of new poxviruses remain as intracellular mature viruses (MVs).
• A small proportion of MVs mature into extracellular viruses (EVs).
• MVs can enclose themselves in Golgi-derived cisternae which adds additional lipid layers and viral proteins.
• Wrapped viruses (WVs) have two bilayer membranes and are transported to the plasma membrane with aid of actin tails. The outer viral envelope membranes fuse with the cell membrane releasing the extracellular virus, EV. EV can remain attached to the cell membrane.
• Vaccinia viruses and some others produce actin comet tails induced by viral proteins for actin depolymerization. These are used for propulsion out of host cells.

This quiz covers the essential features of poxviruses, a family of viruses that infect both vertebrates and invertebrates. It details their unique structure, the two forms they exist in, and the diseases they cause in humans. Learn about the different subfamilies and their impact on health and disease.