Micro: Basics of Virology Flashcards
T/F: Viruses are obligate intracellular parasites that replicate by self-assembly of individual components rather than by binary fission.
True
T/F: Viruses can make energy and proteins independent of a host cell.
False. Viruses CANNOT make these independent of a host cell.
T/F: Viruses contain a genome of limited size that contains both RNA and DNA.
False. Either RNA or DNA, but not both.
What is a virion?
A single virus particle.
List the 4 variations in viral genome structure (i.e. circular, linear, ds, ss…)
1) circular or linear single-stranded (ss) RNA
2) linear double-stranded (ds) RNA
3) linear ss DNA
4) circular or linear ds DNA
What is +RNA?
genomes that are the same sense as messenger RNA (mRNA)
What is -RNA?
genomes that are the OPPOSITE sense as mRNA
Some RNA viruses contain segmented genomes. What are these analogous to in eukaryotes?
effectively like several chromosomes within a single virion
In general, DNA genomes are larger or smaller than RNA genomes?
Larger
Virus genomes are packaged in protein shells known as:
Capsids
Are capsids malleable or rigid?
rigid
Capsids are the result of self-assembly of virally-encoded ________ .
capsomers
List the 3 forms of capsids.
helical
icosahedral (spherical)
complex
Is the shape of the capsid dictated by the shape of the genome or by the capsomers that self-assemble?
Capsomers
genome + capsid = ?
nucleocapsid = virion for “naked” viruses
A nucleocapsid surrounded by a lipid membrane is referred to as a virion for “______” viruses.
virion for “enveloped” viruses
What are inserted in the membrane of viruses and serve as virus attachment proteins and membrane fusion proteins?
Virally-encoded glycoproteins
Because the envelope of an “enveloped” virus is mostly lipid, enveloped viruses are more or less stable than “naked” viruses? Why?
Less stable. More susceptible to drying. Sensitive to detergents and alcohols. Cannot survive in the GI tract.
Which type (naked or enveloped) of virus spreads in large droplets, secretions, organ transplants, and blood transfusions?
enveloped viruses
Please list the 8 steps in viral replication.
Attachment Penetration Uncoating Early Transcription and synthesis of nonstructural proteins Genome replication Late transcription and synthesis of structural proteins Assembly of virus particles Release of virus particles
What are the two modes of penetration of viruses with their host cell?
endocytosis
membrane fusion
During the early transcription step of viral replication, do RNA viruses use host RNA polymerase?
No. Virally-encoded RNA-dependent RNA polymerase.
During the early transcription step of viral replication, do DNA viruses use host or self RNA polymerase?
Use host RNA polymerase (except poxoviruses)
Genome replication of RNA viruses occurs where in the host cell?
cytoplasm
Genome replication of DNA viruses occurs where in the host cell?
Nucleus (except poxoviruses and hepadnaviruses)
What causes the virions to be “released”?
host cell lysis or budding in the case of enveloped viruses.
List the 6 forms of viral cytopathogenesis.
1- inhibition of cellular protein synthesis
2- inhibition and degradation of cellular DNA
3- alteration of cell membrane structure
4- disruption of cytoskeleton
5- formation of inclusion bodies (typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins)
6- toxicity of virion components
T/F: +RNA virus genome functions as mRNA and is immediately translated by cellular ribosomes.
True
T/F: -RNA virus genome functions as mRNA and is immediately translated by cellular ribosomes.
False. -RNA virus genome CANNOT be used as mRNA; must be used as a template to transcribe a +RNA (mRNA) strand
Where does the RNA-dependent RNA polymerase come from that transcribes -RNA strands from the +RNA genome?
It is one of the individual proteins cleaved from the translated +RNA polyprotein
What are used as templates to make many copies of the +RNA genome?
-RNA strands
+RNA or -RNA copies are used as mRNA to make structural proteins and are encapsidated to produce nucleocapsids?
+RNA.
To transcribe the -RNA genome, the incoming virus particle carries a _______________ .
RNA-dependent RNA polymerase
What is the result of transcribing a -RNA strand?
A +RNA strand (mRNA)
Newly produced -RNA genomes are encapsidated to produce __________ .
nucleocapsids
Retrovirus particles carry an RNA-dependent _____ polymerase aka reverse transcriptase aka host genome hijacker aka Al-Qaeda of the Viral Realm.
RNA-dependent DNA polymerase
What does RNA-dependent DNA polymerase do, exactly?
+RNA genome is REVERSE TRANSCRIBED into dsDNA and integrated into the host genome. Then, retrovirus proteins and +RNA genome are transcribed by host enzymes. CRAZYYY
DNA virus (except poxvirus) genomes are transcribed by host ___________ .
host DNA-dependent RNA polymerases
T/F: Many viruses have a host shut-off mechanism that degrades host mRNAs.
True
Many viruses use specific transcription factors that REDIRECT host polymerases to _____ genes and away from ______ genes.
viral; cellular (host)
Viral genome replication is dependent on _______________ for LARGER viruses but smaller viruses use host DNA polymerase.
virally-encoded DNA-dependent DNA polymerase
Newly produced DNA genomes are _______ to produce nucleocapsids.
Encapsidated
When measuring viral growth in the lab, a plaque refers to what, exactly?
Many viruses lyse infected cells and the resulting “hole” in a confluent monolayer of cells is called a plaque
What is a lysate?
The suspension of virions in culture medium that results from unrestricted growth of the virus on a cell monolayer.
Are all virus particles produced in a lysate infectious?
Nope
The ____________ measures the number of physical particles compared to the number of infectious virions.
particle-to-pfu (plaque forming unit) ratio
________ measure the number of infectious virions in a given volume of lysate.
Plaque assays
What is the basic unit of infectivity in a biological assay of virions.
plaque-forming units (pfu) per ml of lysate
What is multiplicity of infection (MOI)?
the ratio of the number of infectious particles to the number of target cells to be infected
An MOI of 1 will only infect about ___% of the cells in a monolayer.
60%
An MOI of between ___ and ___ is needed to ensure that all the cells are infected.
5-10
A single-cycle growth curve can be divided into two peroids:
Eclipse period and latent period
Describe what is going on during the eclipse period of a single-cycle growth curve.
Post-penetration phase until virus can be detected intracellularly
Which phases of the virus replication cycle are present in the eclipse period of the single-cycle growth curve?
Corresponds to uncoating, early transcription, and genome replication steps; ends at virus assembly.
Describe what is going on during the latent period of a single-cycle growth curve.
post-penetration phase until virus can be detected extracellularly. Yes, includes the eclipse period.
Which phases of the virus replication cycle are present in the latent period of the single-cycle growth curve?
Corresponds to uncoating, early transcription, genome replication, virus assembly, and release.
Why do viral genome mutations occur at a relatively high frequency?
In part due to the large number of genome copies produced in ever infected cell. Also due to polymerase errors, especially for RNA viruses.
What is complementation?
an exchange of proteins
Briefly describe complementation.
If a genome with a lethal mutation in gene “X” arises along with the wild-type genome in the same cell, then the wild-type copy of the gene X can provide the function for the mutant genome. Mutant genome will be packaged into a capsid and will go on to infect a second cell upon release. However, the mutant will not be able to replicate in the second cell because its genome still contains the lethal mutation in gene X.
What is recombination?
An exchange of genetic material on the same segment of genome
How is recombination good for clearing mutations from a genome?
If a genome with a lethal mutation in gene X arises along with the wild-type genome in the same cell, then the mutation can be removed by recombination with the wild-type gene X. As a result, the virus will be able to replicate in a second cell because it now contains a wild-type genome.
T/F: recombination occurs frequently with DNA viruses.
True
Does true recombination occur with RNA viruses?
No, but they can exchange genetic material in a way that resembles recombination.
What is reassortment?
An exchange of genetic material on different segments of genome
Briefly describe the reassortment of genes and how it is significant to strain variation.
If two SEGMENTED viruses infect the same cell, they can exchange some of their segments at the time of virus assembly. As a result, a NOVEL strain of virus that is composed of segments from both of the “parents” can be released from the infected cell. Important mechanism for the generation of new influenza strains.
What is the most common route of infection by viruses?
Inhalation
Initial replication is in cells that express _____ receptors and contain appropriate cellular factors for replication.
viral receptors
Localized spread of the virus can be achieved in two ways, describe them.
1- Release of virus from an infected cell and subsequent infection of surrounding cells.
2- Some enveloped viruses can fuse an infected cell with uninfected cells to directly spread to surrounding cells (syncytia formation). MIND BLOWN
T/F: viruses may spread from the original site of infection by gaining access to the bloodstream or lymphatic system.
True
What is viremia?
The presence of virions in the blood
Viruses can gain access to the CNS by 3 mechanisms: circumventing the BBB, through CSF, or by direct uptake in ____________ .
circumventing the BBB
through CSF
direct uptake in peripheral nerves
An incubation period of ______ is a short incubation period and is characteristic of viruses that do not require secondary spread for symptomology.
1-2 days
_______ is usually the minimum incubation period for viruses that require secondary spread.
12-14 days
Are patients infectious during the incubation period? (unknowingly spreading the virus to others)
They can be
What is the acute phase of an infection?
The symptomatic phase of infection.
Name and describe the 3 forms of persistent viral infection.
Chronic- virus is produced at low levels, but may not continue to cause disease symptoms (Hep B)
Latent- virus genome remains in cells indefinitely, but virus particles are not produced, except during reactivation (herpes)
Transforming- intact or partial virus genome integrates into cellular DNA or is otherwise maintained in the cell and immortalizes the cell, alters its growth properties (oncogenic)
a. RNA viruses: retroviruses, hep C virus
b. DNA viruses: hep B, papilloma virus, polyoma virus, adenovirus type 2, Epstein-Barr virus, human herpesvirus-8, pox
Describe the first defense to viral infection by the immune system.
1- Nonspecific immune response, including NK cells and IFN
2- PRRs recognize viral PAMPs to induce IFN-alpha/beta
3- IFNs bind to surrounding, uninfected cells and induce pathways that prevent virus replication
What is the main viral PAMP?
dsRNA
Describe the 3 ways that IFNs induce surrounding uninfected cells to resist infection and thus prevent viral replication.
1) Protein kinase (PKR) pathway inactivates translation initiation factor eIF-2, inhibits viral protein translation.
2) 2-5A system activates RNase L which cleaves RNA, destroying RNA genomes or inhibiting viral transcription.
3) Mx pathway proteins are GTPases that inhibit RNA polymerase activity.
List the 2 antigen-specific responses (cellular and humoral) that arise several days postinfection.
1) CD8+ T cells are the major cellular response to primal viral infections; infected cells are targeted for lysis through antigen presentation.
2) abs can neutralize virus binding or facilitate the lysis of enveloped viruses with complement.
Explain why children defective in ab production are not more susceptible to viral infections.
This is due to the importance of cellular immunity compared to humoral immunity in fighting viral infection.
List 4 ways that viruses evade immune defenses.
1- antigen variation to escape humoral response 2- inhibition of antigen presentation to escape cellular response 3- cytokine homologs that down regulate or block cellular response 4- latent infection in neurons where there is no class I MHC
List the 3 types of antivirals
vaccines
immune globulin
drugs
Under what viral conditions would a vaccine not be practical?
Many strains of the virus (serotypes) and if the virus undergoes much antigenic variation due to high mutation rates in a dominant antigenic structure
List the 3 basic types of viral vaccines.
1- live, attenuated virus
2- killed virus
3- subunit (recombinant DNA)
Do attenuated vaccine strains produce symptoms?
Yes, subclinical infections
What are the advantages of attenuated vaccines?
cheap Strong response (IgG, IgA, T cell) that is long lasting
What are the disadvantages of giving an attenuated vaccine?
can be labile in transport
cannot be given to immunocompromised pts
can revert to virulence in rare cases
Can a killed virus cause illness?
No
What are the advantages of a killed virus vaccine?
very stable
rare side effects
cannot revert to virulence
What are the disadvantages of a killed virus vaccine?
expensive to prepare
shorter term immunity that is mostly limited to IgG
Subunit vaccines exist for which two virus families?
Hep B and HPV
What are subunit vaccines, anyway?
Composed of single viral proteins that are expressed in yeast using recombinant DNA technology.
What are the advantages and disadvantages of subunit vaccines?
ADV:
cannot cause disease
are not derived from blood
DisADV:
requires multiple injections
T/F: immune globulin is used in both pre- and post exposure prophylaxis.
True
