Poxviruses Overview

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Questions and Answers

What material was used in the process of variolation?

Material from smallpox sores (correct)

Saliva from infected individuals

Blood from infected individuals

Fluid from chickenpox blisters

Who developed the vaccination procedure for smallpox in 1796?

Edward Jenner (correct)

Jonas Salk

Robert Koch

Louis Pasteur

What virus replaced cowpox in the smallpox vaccine by the mid-1800s?

Herpes simplex virus

HIV virus

Vaccinia virus (correct)

Variola virus

Why did milkmaids not show symptoms of smallpox after variolation?

They had been vaccinated with cowpox Signup and view all the answers

What is considered one of the biggest achievements in international public health?

The eradication of smallpox Signup and view all the answers

What is the shape of poxvirus particles?

Oval or brick-shaped Signup and view all the answers

Which subfamily of poxviruses infects vertebrates, including humans?

Chordopoxvirinae Signup and view all the answers

What was the average case fatality rate of smallpox in endemic countries?

25% Signup and view all the answers

During which phase of smallpox infection does fever and rash suddenly onset?

Initial acute phase Signup and view all the answers

What historical evidence suggests the early existence of smallpox?

Scars on Egyptian mummies Signup and view all the answers

What vaccination concept was developed from variolation?

Immunization Signup and view all the answers

What is the mode of transmission for smallpox during the initial respiratory infection?

Airborne through secretions Signup and view all the answers

Which of the following conditions is an existing natural poxvirus infection of humans?

Molluscum contagiosum Signup and view all the answers

What is the role of the vaccinia virus in relation to smallpox?

It is used for smallpox vaccination. Signup and view all the answers

What is a unique feature of the poxvirus genome?

It has covalently closed hairpin ends. Signup and view all the answers

Which two institutions currently hold the world's stocks of live variola virus?

CDC in Atlanta and VECTOR Institute in Russia Signup and view all the answers

What is the size range of the poxvirus genome?

150-250 kb Signup and view all the answers

What type of genes are required for the replication of DNA in poxviruses?

Early genes Signup and view all the answers

What happens to the viral core during the initial stages of infection?

It is dissolved by early viral proteins Signup and view all the answers

How many proteins can potentially be produced by the genes in the poxvirus genome?

Up to 100 proteins Signup and view all the answers

What characteristic of the poxvirus genome aids in its transcription process?

Absence of introns Signup and view all the answers

Where does the replication of viral DNA in poxviruses primarily occur?

Cytoplasm Signup and view all the answers

What is the function of the tubular structure within the poxvirus core?

Containing the DNA Signup and view all the answers

What are concatemer junctions produced by poxviruses?

Oligomers of genome length units Signup and view all the answers

What distinguishes the two infectious forms of poxvirus?

Their membrane composition Signup and view all the answers

What is the role of virus-coded resolvase in poxviruses?

To resolve concatemers into monomers Signup and view all the answers

How are hairpins involved in the DNA synthesis process of poxviruses?

They are used for further DNA synthesis after being refolded Signup and view all the answers

What structure is formed during the synthesis of the entire genome in poxviruses?

Head-to-head dimer Signup and view all the answers

What is the initial event that occurs after viral DNA is released into the cytoplasm?

Expression of early mRNAs and proteins Signup and view all the answers

What is the primary function of the actin ‘comet’ tails produced by Vaccinia viruses?

To aid in the propulsion and budding of viruses out of the host cell Signup and view all the answers

How do wrapped viruses differ from other viruses in terms of structure?

They have two bilayer membranes derived from Golgi apparatus Signup and view all the answers

What role do the outermost viral membranes have in the release of extracellular virus?

They fuse with the cell membrane, releasing the virus Signup and view all the answers

What cellular structures do extracellular viruses remain attached to after their release?

Microvilli projections of the cell membrane Signup and view all the answers

What is one function of the proteins made by poxviruses in relation to host defenses?

To target and counteract host defense mechanisms Signup and view all the answers

What initiates the transcription of intermediate genes in poxviruses?

Two viral initiation transcription factors (VITFs) and one cellular factor Signup and view all the answers

Which of the following features characterize postreplicative mRNAs in poxviruses?

They have poly(A) extensions and 3' end heterogeneity Signup and view all the answers

What is the first stage in the assembly of vaccinia virions?

Synthesis of crescent-shaped membrane structures Signup and view all the answers

What are immature virions characterized by during their development?

Development of internal core and lateral bodies through rearrangement Signup and view all the answers

How does the transcription initiation process differ for late genes in poxviruses compared to intermediate genes?

Late genes require three VLTFs and an additional early gene product Signup and view all the answers

What role do small vesicles, or micelles, play in the assembly of vaccinia virions?

They deliver lipids containing viral envelope proteins to crescents Signup and view all the answers

What determines which virions remain intracellular versus those that become extracellular?

The majority remain as intracellular MVs, while a small portion matures to EV Signup and view all the answers

Which process occurs during the transcription initiation of mRNAs in poxviruses?

A slippage mechanism that adds poly(A) extensions Signup and view all the answers

Study Notes

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.

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Description

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.