Chapter 4 Flashcards
What is the difference between viruses and bacteria with respect to cause of disease?
Viruses are unique in that the diseases they cause are most often a direct effect of the replication of the virus on its host Bacterial diseases are usually the result of the toxic effects of released products of the bacterium’s metabolism in its host
What is the difference between the ‘one-step growth curve’ in viruses and bacteria?
Bacteria are immediatelty detected, but viruses are undetected for a period of time when they are replicating because they are in the cell
What are the three events that occur during the one-step growth curve?
entry phase, eclipse phase, release phase
What occurs in the entry phase of the one step growth curve?
the virus binds to the cell receptor and enters the cell
What occurs in the eclipse phase of the one-step growth curve?
the virus genome has been uncoated, and no infectious virus can be recovered - biosynthesis of the virus’ nucleic acid and protein occurs
When does the eclipse phase end?
when progeny are released from the cell
What occurs during the release phase of the one step growth curve?
progeny virus particles are assembled and released
What are the steps of the virus replication cycle?
attachment, penetration, uncoating, biosynthesis, assembly, and release
What is a virus receptor?
cell-surface molecules that bind the incoming virus to the cell, and in addition, promote entry
What is a virus attachment protein?
the virus ligand that binds to the host cell receptor
In non-enveloped viruses, what is the viurs attachment protein?
the capsid
In enveloped viruses, what is the virus attachment protein?
the attachment protein is most often a glycoprotein inserted into the viral envelope
What is the role of the virus receptor in tissue specificity and species specificity?
they are the primary determinants of host susceptibility
What is the role of the virus receptor in emergence of canine parvovirus?
The emergence of canine parvovirus was due to mutations in the capsid gene of the feline parvovirus. This mutation allowed the feline parvovirus attach to canine cells.
What is the difference in binding affinity between a primary receptor and a co-receptor?
binding to a primary receptor usually has higher affinity and specificity than binding to a co-receptor
Why would a virus choose to bind to a co-receptor?
because co-receptors may aid in viral strategies of immune evasion
How do co-receptors aid in virion entry?
they trigger fusion and/or penetration
What is neutralization of a virus?
the process by which antibody, binding to a virion, renders it non-infectious
What does neutralization prevent a virus from doing?
initiation/completing the replication cycle
Viruses can penetrate the cell at the plasma membrane or from within a vacuole. How do viruses become vacuolated within a cell? Is this specific for enveloped or non enveloped viruses?
They enter via receptor-mediated endocytosis, and both non-enveloped and enveloped viruses use this method
If a virus is already in the endocytic vesicle, why is membrane fusion necessary?
Because although it is in the endocytic vesicle, it technically is still outside of the cell. In order to begin uncoating, the virus must penetrate the membrane of the vacuole
Membrane fusion only occurs with ______ viruses.
enveloped
What is membrane fusion mediated by?
the viral fusion protein
What is the role of the fusion protein in virus penetration?
they are viral-coded proteins that induce the two membranes to fuse, so that the viral capsid and/or nucleic acid can enter the interior of the cell
What are the mechanisms for activation of the fusion protein?
Cleavage by cellular protease, low pH in endosome, or receptor binding-induced conformational change
Why can cellular proteases affect tissue distribution and pathogenicity (influenza was used as the example)?
If an enveloped virus that needs to penetrate via protease cleavage attaches to a cell that does not have the appropriate protease that will cleave it in the correct spot for its fusion protein to show, then it will not be able to enter the membrane and uncoat.
The pathogenicity is entirely dependent on the availability of the protease needed for cleavage.
How does the low pH in an endosome reveal the fusion protein?
The low pH within the endosome can trigger conformational changes in the viral glycoprotein that leads to the exposure/movement of the fusion peptide
What process do non-enveloped viruses use to penetrate the host cell?
permeabilization via membrane puncture, perforation, or lysis
Describe the process of membrane puncture.
Virus particle generates a pore in the membrane through which the genome is selectively released into the cytosol. The capsid does not enter the cytosol.
Ex: Picornaviruses
Describe the process of perforation.
The entire capsid is transferred through the membrane without major lysis of the membrane
Ex: Parvovirus, Rotavirus
Describe the process of membrane lysis.
The virus particles induce breakage of the membrane of cytoplasmic organelles, allowing the virus to be released into the cytosol
Ex: Adenovirus
What is uncoating?
the process of removal of the capsid and liberation of the genome to expose it for the biosynthesis of viral proteins and nucleic acids
Where can uncoating occur?
at the plasma membrane or nuclear membrane
When can uncoating occur?
upon the release from the endocytic vacuole in the cytoplasm or simultaneously with penetration
What can inhibit uncoating?
antibody or by modification of the pH of the microenvironment
What are 2 categories of products that myst be synthesized to complete the replication cycle?
- proteins that make up the virion structure 2. New genomes for packaging into virions
Why must all viruses express their genes as functional mRNAs in order to replicate?
because they need the host cell’s translational machinery in order to replicate
What are 2 advantages of temporal regulation of gene expression by a virus?
Highly antigenic structural proteins are not expressed until genome replication is complete and ready for packaging and release
There is less competition with the host cell for gene expression
DNA viruses display temporal regualtion of virus gene expression. What occurs during immediate early gene expression and when does this occur?
The gene expression occurs at the start of an infection and encodes for transcription factors that enhance expression of viral early genes.
DNA viruses display temporal regulation of virus gene expression. What happens when ‘early genes’ are expressed and when does this happen?
‘Early genes’ are expressed prior to DNA replication and encode for non-structural proteins required for DNA replication and genes for modulation of the host cell environment.
DNA viruses display temporal regulation of virus gene expression. What happens when ‘late genes’ are expressed and when are they expressed?
‘late genes’ are expressed after DNA replication and are involved in the direc synthesis and assembly of structural proteins
What are the two biochemical pathways that RNA viruses can utilize for their own replication?
- RNA-dependent-RNA synthesis (RNA replication
- RNA-dependent-DNA synthesis (reverse transcription)
True or False: Most RNA viruses use temporal regulation of gene expression during the replication cycle.
False - In most RNA viruses, all virus genes are expressed at roughly the same level throughout the replication cycle
What RNA viruses use reverse transcription?
Retroviruses (some of these use temporal regulation of gene expression)
What 3 strategies are used by RNA viruses to compete with the host cell for gene expression at the level of translation?
- Interference with formation of the 5’-methyl guanosine cap on the cellular mRNA
- Removal of the 5’-cap from the cellular messenger RNA molecules and using it on the virus’ own messenger RNA
- Utilize internal ribosome entry sites (IRES) that directly bind eIF-4G to initiate treanslation
How can the strategies that RNA viruses use to compete with the host cell for gene expression be clinically relevant?
It is not something that normal cells do, therefore they also represent potential sites of action for antiviral drugs
What is genome relplication by RNA viruses defined as?
the production of progeny virus genomes
What does replication of viral RNA require first?
the synthesis of complementary RNA, which then serves as a template for making more viral RNA
Why is reverse transcriptase a good candidate for antiviral drugs?
Because during reverse transcriptase, there is a lack of proof reading and a high error rate. If the cleavage sites are targeted, mistakes in reverse transcriptase can be made and not fixed
Why does the size of the viral genome have implications for viral replication strategies and viral pathogenesis?
The size of the virus is dependent on what phase the cell is in in order to replicate
Ex: Small DNA viruses requires cells to be in the S phase in order to replicate
The size of the virus also has implications on how it will replicate.
Ex: For dsDNA viruses that replicate in the nucleus, transcription of viral mRNAs is carried out by cellular RNA polymerase II, but for large dsDNA viruses that replicate in the cytoplasm, viral mRNAs are transcribed by a viral transcriptase
How can the viral strategy of post-translational modification of viral proteins be used to safely restrict viral replication?
Many virus proteins are translated as precursor poly proteins, which are subsequently cleaved by viral or cellular proteases. Antiviral drugs can target these cellular proteases to inhibit them and prevent virus proteins from being cleaved.
List 4 basic events that occur during virion assembly.
- Formation of indivisual structural units of protein shell
- Self-assembly if the protein shell through interactions among structural units
- Selective packaging of nucleic acid genome and other essential viral components
- Acquisition of an envelope - only for enveloped viruses
Where does replication of RNA viruses occur? DNA viruses?
RNA viruses: cytoplasm (except retroviruses and Orthomyxoviruses, plus pox viruses)
DNA viruses: nucleus (except pox viruses, plus Orthomyxoviruses)
Both compartments: Retroviruses, Hepadnaviruses
What is the sole way out of the cell for non-enveloped viruses?
the cell must die and the cell membrane must degrade sufficiently that the virions are released
