Lecture 28: Virology III Flashcards
What are the 7 Baltimore classes of viruses?
- dsDNA
- (+) ssDNA
- dsRNA
- (+) ssRNA
- (-) ssRNA
- ssRNA-RT ((+) RNA viruses that replicate through DNA intermediate)
- dsRNA-RT (dsRNA viruses that replicate through a ssRNA intermediate)
What Baltimore classifications have reverse transcriptase?
6 and 7 (the retroviruses)
What type of virus is class 1?
Double-stranded DNA viruses.
Give an example of a class 1 virus.
Adenovirus or herpes simplex
Where do group 1 viruses replicate?
In the host cell nucleus.
Describe how class 1 viruses replicate.
Their viral mRNAs are synthesized from the viral DNA using the host’s RNA polymerase II. The double stranded DNA genome is immediately transcribed into mRNA upon entry.
Give an example of a class 1 virus that replicates differently and explain how.
The Poxvirus family, which replicate outside the nucleus. They encode their own RNA-dependent RNA polymerase.
What are class 2 viruses?
Single-stranded DNA viruses
Give an example of a class 2 virus.
Parvovirus
Where does the replication of class 2 viruses take place?
In the host nucleus.
Describe the genome of class 2 viruses and how it gets replicated.
Most have circular genomes that are first turned into a dsDNA intermediate, the complementary strand generated by a DNA polymerase. Viral mRNAs are then transcribed from the dsDNA using the host transcription machinery (polymerases)
Would class 2 viruses be expected to be more or less stable than class 1 viruses? Why?
Class 2 viruses are less stable than class 1 because they are single stranded.
What are class 3 viruses?
Double stranded RNA viruses.
Where do class 3 viruses replicate?
In the host cytoplasm.
Give an example of a class 3 virus.
Reovirus.
Describe how class 3 viruses replicate.
An RNA-dependent RNA polymerase (RdRP) makes (+) single-stranded mRNAs using the - strand for the dsRNA as a template.
What are class 4 viruses?
Single-stranded (+) RNA viruses.
Give an example of a class 4 viruses.
Poliovirus and HCV
Where do class 4 viruses reproduce?
In the cytoplasm.
Describe how class 4 viruses reproduce.
The positive RNA genome of these viruses can be used directly by the host ribosomes to synthesize viral proteins, but this is not sufficient. The first proteins generated (RdRP) will generate a -RNA from the +RNA, which will be used as a template to make more copies of the +RNA.
What are class 5 viruses?
Single stranded (-) RNA viruses
Give an example of a class 5 virus.
Influenza virus
Where does the replication of class 5 viruses take place?
In the cytoplasm
Describe how the replication of class 5 viruses takes place.
The (-) RNA genome cannot be used by host ribosomes, so they must have an RdRP in their capsid so that the genome can be synthesized into (+) mRNAs.
What are class 6 viruses?
(+) single-stranded RNA viruses that replicate through a DNA intermediate.
Give an example of a class 6 virus.
Retroviruses.
What is the defining feature of class 6 viruses?
The use of the viral reverse transcriptase to convert the (+) RNA into dsDNA.
Describe how the replication of class 6 viruses occurs.
Instead of using the (+) RNA directly for making viral proteins, they insert the dsDNA copy of the viral genome generated by the RT into the host genome using the viral genome integrase. The integrated “provirus” is then used as a template to make mRNAs/(+)RNAs by the host cell transcription machinery.
Describe the role of RT in class 6 viruses.
It creates a DNA copy from the +ss mRNA, first by creating a DNA/RNA hybrid, then by degrading the RNA and creating a complementary strand to the DNA.
What is a provirus?
Applies to class 6: once the viral genome has integrated into the host cell’s genome. It will get expressed and transcribed like any other part of the genome.
What are class 7 viruses?
Double-stranded DNA viruses that replicate through a single-stranded RNA intermediate.
Give an example of a class 7 virus.
Hepatitis B virus
Describe the genome of class 7 viruses.
They have a double-stranded, gapped genome.
Describe how class 7 virus replication occurs.
Their gapped dsDNA genome enters the nucleus and is filled in to form a closed dsDNA episome, which then serves as a template for the production of viral (+) mRNAs. The episome is also transcribed into pregenome +mRNA in the nucleus, which then exits into the cytoplasm in the virus. The +mRNA gets reverse transcribed into gapped DNA once again (the RT will leave a gap), and this is the final genome that will exit the cell.
Viral mRNAs are always made by transcription of either […] or […]
dsDNA or (+) RNA
Which viral groups require an RdRP to replicate their genome and synthesize viral mRNAs?
3, 4, and 5
Compare groups 3, 4, and 5 in terms of how they use RdRP.
Group 4 will generate RdRP first, since its genome (+) RNA can be used directly by the host ribosomes. For groups 3 and 5, their genome cannot be directly used, so they must bring RdRP in their capsid to initiate their replication cycle.
What is the capsid of a virus?
It is the protein shell around the viral genome.
What is the nucleocapsid of a virus?
It is the complex of the capsid + the nucleic acids in the capsid.
What is the envelope of a virus?
It is a host-derived phospholipid bilayer surrounding the capsid. It may contain viral transmembrane glycoproteins that form spikes.
What is a virion?
An infectious viral particle (versus the infected cell, the other part of the life cycle)
What are the 2 main functions of the capsid?
To protect the genome and to deliver the genome into the host cell.
Describe how the capsid is involved in the protection of the genome.
The capsid packages the nucleic acid genome and interacts with the host cell membrane to form the envelope as the virion leaves the cell.
Describe how the capsid is involved in the delivery of the genome.
The binding between the virion and the target cell surface receptor is done through the spike proteins or, if no spike proteins, through the proteins in the capsid itself.
What are helical viruses? Describe the characteristics of their capids.
They are viruses whose capsid is spiral in shape. The capsid is usually flexible and rod-like.
What determines the length of a helical capsid?
It is usually determined by the length of the nucleic acids.
Describe the structure of a helical capsid.
The capsid proteins are bound to each other so as to form as ribbon-like structure. This structure folds into a helix because the proteins are thicker at one end than at the other.
Is the interior of a helical capsid acidic, basic, or neutral? Why?
It is basic because it needs to interact with the nucleic acids inside.
What type of genome can be packaged inside a helical capsid? Why?
Only single-stranded RNA because of the rigidity of the double-stranded nucleic acids (vs the flexible capsid)
Describe the structure of an icosahedral capsid.
It is made of 20 identical triangular faces, 30 edges and 12 vertices. It approximates a sphere and is quite rigid.
What type of genome can be packaged inside an icosahedral capsid? Why?
They can be used to package either single- or double-stranded RNA and DNA, as they are quite rigid.
How many pentamers and/or hexamers are needed to construct larger icosahedral capsids?
There are always 12 pentamers, but an increasing number of hexamers can be used to increase the size of the icosahedral capsid.
What determines the size of the icosahedral capsid?
Often, the size of the genome, where larger genome = larger capsid to contain it.
What is a complex virus?
A virus where the capsid symmetry is neither icosahedral nor helical.
Give an example of the most important complex virus. What is its shape?
Poxviruses. They are usually described as brick-shaped.
How is the envelope of a virus acquired?
It is acquired by budding of the nucleocapsid through a cellular membrane.
Do all viruses have an envelope? Explain.
No. Those lacking an envelope are called “naked” viruses.
How does the stability of naked viruses differ from taht of enveloped viruses?
Naked viruses tend to be more stable and more resistant to harsh environmental conditions than enveloped viruses.
What is tomography?
It is an imaging technique where sections of a sample, such as viral glycoproteins, are obtained through the use of a penetrating wave such as x-rays. These images and then used for 3-D dimensional reconstruction of the sample.
The stability of viral particles can be described as […]
Metastable.
What is the purpose of metastability of viral particles?
The capsid must be sufficiently stable to protect the viral genome, but must become unstable upon infection to release the viral genome inside the infected cell.
Explain the two components of how metastability is achieved in the capsid.
Metastability consists of a stable structure and an unstable structure.
Stable structure is created by the symmetrical arrangement of identical proteins to provide maximal contact.
Unstable structure refers to the weak, impermanent nature of the protein bonding such that the capid can be taken apart or loosened to release the viral genome.
The process by which the viral capid structure becomes unstable once it gets into a cell is called […]
Proteolysis.
