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Creighton Virology

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A virus is made up of ________ & _________
genes (RNA or DNA) & protein-containing coat
One (complete) virus particle
Virion
A virus is an __________ parasite
intracellular
viruses are _____-_____ times smaller then the cells they infect
100-1000
The smallest virus
parvovirus (20 nm)
The largest virus
poxvirus (300 nm)
The ability of viruses to pass through ______ is used to ID an unknown infectious agent as a bact or virus.
filter
The viral genome can be ______ or ______ stranded
double, single
The viral genome can have 3 basic morphologies
linear, circular, segmented
Retroviruses have a ______ genome
diploid (2 identical copies of the genome - i.e. HIV)
The _____ is the association between nucleic acid & basic proteins either coded by the virus or histones from the host cell
core
The association of core proteins & the genome is required to _______ the viral genome during viral ______ & virion _______
condense, assembly, formation
The protein shell directly surrounding the viral nucleic acid.
Capsid
The complete protein-nucleic acid complex that is the packaged from of the genome in a virus particle
Nucleocapsid
The capsid & nucleocapsid are composed of ___ or at most ___ different kinds of proteins in a crystalline array. Why?
1, a few. Small genome - rest of genome for intracellular activity
The lipid bilayer & associated glycoproteins that surround many types of virus particles
Envelope
Protein or glycoprotein structure(s) which emanates from the surface of the virus particle
Spikes
Virion structural protein which locates on the cytoplasmic side of the transmem glycoprotein spike. It attracts the completed nucleocapsid for mem fusion.
matrix protein
The structure of the capsid &/or envelope (spikes) has important implications for (3 things)
adsorption, hemagglutination (used for ID), recognition of viruses by neutralizing antibodies
The symmetry observed w/ cylindrical viruses (like a slinky)
Helical symmetry
The simplest viral symmetry (proteins bind to nucleic acid not a capsule)
Helical symmetry
The capsid of a virus composed of many copies of a single kind of protein subunit arranged in a close-packed helix
Helical symmetry
Helical symmetry examples (5)
influenza, measles, mumps, rabies, poxviruses (also tobacco mosaic virus - non animal)
Can helical particles form w/o the genome?
No
Symmetry observed w/ spherically shaped viruses. Involves the packing together of many identical subunits. (soccer ball)
Icosahedral symmetry (or cubic symmetry)
Morphological subunits that can be seen when capsid is broken (hard to "see" in an intact virus). Surface structures composed of 5-6 protein molecules
Capsomeres
Enveloped virus w/ icosahedral symmetry, the _____ is surrounded by the ________. An example is ______
capsid, envelope, herpes
Enveloped virus w/ helical symmetry, the _____ is coiled w/in the ________. An example is ______
Nucleocapsid, envelope, orthomyxoviruses (influenza)
No clearly identifiable capsid. But several coats around the nucleic acid. An example is _______
Complex virion, poxviruses
Steps to multiply a virus
cell entry, genome replication, viral particle assembly, Egress (escape from host cell)
What definition? The kinds of tissue cells and animal species that a virus can productively infect.
Host Range
What definition? The spectrum of cells which can be productively infected by a given virus.
Tissue tropism
What definition? The capacity of a cell or animal to become infected.
Susceptibility
Cells that become immediately infected are susceptible cells at the ______ ___ __________.
Portal of Entry
What are the cells called that are targeted by the virus and result in clinical disease?
Target cells (ie CNS and HSV)
T or F: Sometimes the target cells are at the portal of entry.
TRUE (ie, influenza, gets into airway and stays there)
What determines host range? (2 things)
1. Cellular Receptors (specificity of attachment); 2. Host intracellular factors
Name the 5 types of Infections:
1. Productive; 2. Abortive; 3. Latent; 4. Viral transformation; 5. Lytic
What type of infection: The infection of a receptive cell with a virus particle which results in the MULTIPLICATION of infectious viral progeny.
Productive
What type of infection: The infection of a cell which does NOT result in the multiplication of infectious viral progeny.
Abortive
What type of infection: The virus persists in the cell in a noninfectious form.
Latent
What type of infection: The abnormal growth of cells resulting from the continuous expression of one or more viral genes.
Viral Transformation
What type of infection: The infection and subsequent lysis of susceptible cells by a virus.
Lytic
What is the singlemost important thing produced by viruses that gives them the ability to multiply and determines the fate of the infected cell?
The synthesis and function of the VIRAL PROTEINS
The reproductive cycles of ALL viruses exhibit what common feature?
One-step growth curve
T or F: Growth and assay of viruses requires a high multiplicity of infection (MOI)
TRUE
What definition: The characteristic morphological changes which occur in the cell due to the infection of a particular virus.
Cytopathic Effect (CPE)
T or F: All viruses produce Cytopathic effect (CPE)
False; most do but not all
What is the plaque assay used for?
To determine viral titres; PFU's (show and tell)
What are three methods to use in growth and assay of viruses?
Cytopathic Effect (CPE); Plaque Assay; Molecular techniques (PCR)
What is PCR?
Exponential (2^n) amplification of DNA
What are the 3 steps in PCR?`
1. Denature DNA template; 2. Anneal primers to the DNA template; 3. Primer extension reaction; (after, you run through this cycle tons of times to get lots of copies of the DNA template)
What are the 3 general stages of initiation of infection?
1. Adsorption (attachment); 2. Penetration; 3. Uncoating
In the process of adsorption, what are the cellular receptors composed of?
glycoproteins
Viral _________ are examples of antireceptor molecules
spikes
What is adsorption enhanced by?
multiplicities of attachment and receptor proteins
Differences in host range and tissue tropism are due most often to the presence or absence of ___________.
receptors
How do neutralizing antibodies work?
They are specific for an antireceptor on a virus.
T or F: Penetration is energy dependent (not that type of penetration sickos)
TRUE
What are the three types of entry?
1. Translocation; 2. Receptor-mediated endocytosis; 3. fusion
What type of entry: entire virus crosses plasma membrane (non-enveloped)
Translocation
What type of entry: results in accumulation of virus particles inside cytoplasmic vesicles (ie influenza this way)
Receptor mediated endocytosis
What type of entry: Virion envelope fuses with cellular membrane
Fusion; (ie herpes, measles, HIV)
T or F: The virus can begin replication prior to dismantleling.
False; virus must dismantle first.
What is the process called in the removal of the protective envelope and/or capsid?
Uncoating
The influenza virus is critically dependent on what in order to un-coat and begin replicating?
A low pH. The acidified endosome of receptor-mediated endocytosis releases the nucleocapsid into the cytoplasm.
What is the portion of the cell membrane called that breaks off and surrounds the virus during receptor-mediated endocytosis?
The endosomal vesicle (or just endosome) **It is acidic, which is critical in the release of the nucleocapsid in the influenza virus.
What is the portion of the virus called that is surrounded by the envelope?
The nucleocapsid
What process does the Herpesvirus undergo to enter the cell and undergo de-coating?
Membrane fusion
During membrane fusion, the _________ fuses with the plasma membrane of the host cell, thus releasing the __________ into the cell.
Envelope; Nucleocapsid
What is the KEY event in virus replication?
The synthesis of viral proteins (utilizing the host's protein synthesizing machinery)
Most RNA viruses replicate in the ___________.
cytoplasm
Most DNA viruses replicate in the ___________.
nucleus (except poxviruses)
In order for the virus to replicate, what must it present to the cell?
A viral specific mRNA that the cell can recognize and then translate.
mRNA strands have a ______ polarity.
(positive) +
RNA molecules which are complementary to mRNA have a ______ polarity.
Negative -
The coding DNA strand is always a ________ polarity.
Negative -
What is the process in RNA that removes intervening sequences that do not encode for protein product?
Splicing
What is a long polypeptide chain that is translated from a single transcript with a single ribosome binding site?
Polyprotein
T or F: During encapsidation, self-assembly of component parts occurs in a random fashion
False; it's a stepwise and ordered fashion
During encapsidation, Individual structural subunits or protomeres are preformed into __________ in preparation for final assembly.
Capsomeres
What is the location in the cell where assembly initiates?
The Packaging Site
Where does assembly take place for the herpes virus?
In the Nucleus
Where does assembly take place for the influenza virus?
Cytoplasm
What stages make up the "eclipse (flat line)" state of the one-step growth curve?
Uncoating, replication and assembly, & maturation
What are the 2 ways for release of the virus from a cell?
Cell death--for naked capsid viruses that lack a lysis mechanism (don't need protection of envelope; Budding--acquire their membrane by budding either through the plasma membrane, nuclear membrane (herpes), or golgi or early endosome network (poxvirus)
T or F: The process of viral budding alone will cause cell death.
False; The loss of normal cellular function required for survival is what leads to death.
T or F: Retroviruses can reproduce without cell death.
True, in certain cell types
Which virus(es) are: double-stranded DNA virus that replicates in the nucleus (circular or linear) (3)
Herpesvirus, adenovirus, papillomavirus
Which virus(es) are: double-stranded DNA virus that replicates in the cytoplasm?(1)
Poxvirus
Which virus(es) are: Single-stranded DNA virus? (1)
Parvovirus
Which virus(es) are: Positive-strand RNA virus coding for one genome-sized RNA? (2)
Picornaviruses, Hepatitis C
Which virus(es) are: Positive-strand RNA virus coding for one or more subgenomic mRNAs? (4)
Coronavirus, Togavirus, Calicivirus, Hepatitis E
Which virus(es) are: Retrovirus (1)
HIV
Which virus(es) are: Non-segmented negative-strand RNA virus (3)
Paramyxoviruses (RSV, Measles, Mumps), Rhabdovirus, Filovirus
Which virus(es) are: Segmented Negative Strand RNA virus (1)
Orthomyxovirus (influenza)
Which virus(es) are: Double-stranded RNA virus? (2)
reovirus, rotavirus
Which virus(es) are: Relaxed circular, partially duplexed DNA virus? (1)
HBV
What are the five patterns of Viral Pathogenesis?
1. Acute infection; 2. Latent infection; 3. Chronic Infection; 4. Slow Chronic infection w/out acute infection (ie prions) 5. Transformation (ie Cancer)
Which pattern of viral pathogenesis? Viral infection which is rapidly cleared by host immune response.
Acute infection
Which pattern of viral pathogenesis? Follows acute infection, virus persists in noninfectious form w/ intermittent periods of reactivation & shedding.
Latent infection
T or F: Latent infection viruses (Ie HSV) can cause a productive infection in some cells while simultaneously are latent in other cells
True; (ie epithelial cells & neuronal tissue for HSV)
Which pattern of viral pathogenesis? Follows acute infection, infected cell survives resulting in low level persistent viral production.
Chronic infection
Which pattern of viral pathogenesis? Only one involving prions (no known viruses cause this type of infection).
Slow chronic w/out acute infection
Which pattern of viral pathogenesis? The abnormal growth of cells resulting from the continuous expression of one or more viral genes; cancer.
Transformation
Retroviruses and all major groups of DNA viruses EXCEPT ____________ are associated with the pattern of pathogenesis ____________.
parvoviruses; transformation
What virus? Large, Enveloped icosahedral capsid, Double-stranded linear DNA, Replicates in the nucleus.
Human Herpesviruses
Name the 3 subfamilies of Herpesviradae:
1. Alphaherpesvirinae; 2. betaherpesvirinae; 3. gammaherpesvirinae
List the herpesvirinae groups in order of most variable host range to most limited host range.
Alpha (most variable), Beta, Gamma(most limited
Where does the alphaherpes establish latency?
Primary sensory ganglia
Where does the betaherpes establish latency?
secretory glands, lymphoreticular cells, kidneys, and other tissues
Where does the gammaherpes establish latency?
Lymphoid tissue
Which has a longer reproductive cycle? Alpha or beta herpes?
Beta
Which herpes readily establishes carrier cultures?
Beta
Which herpes is specific for either B or T Lymphocytes?
Gamma
Herpes uses the host cell DNA-dependent RNA polymerase to synthesize ________.
mRNA
In herpes, What does the last cycle of mRNA transcript encode for?
The viral structural proteins. (goes thru 2 or 3 cycles of transcription first)
Where does Herpes double-stranded DNA replicate?
In the Nucleus
What are the 3 common names of the alpha subfamily herpes?
HSV 1, HSV 2, Varicella-Zoster (VZV)
What are the 2 common names of the gamma subfamily herpes?
Epstein Barr Virus, Kaposi's sarcoma
What is the common name of the beta subfamily of herpes?
cytomegalovirus (CMV)
How is herpes transmitted?
direct contact (saliva, vagina, lesion fluid)
What causes herpes to reactivate?
stress; immune suppression
How does herpes avoid antibodies?
by cell to cell spread (syncytia)
What is required for resolution of herpes?
cell-mediated immunity (limited role for antibodies)
T or F: Herpes has a seasonal incidence
FALSE
T or F: Only select few of the stages of viral replication could be a target for antiviral therapy.
False; theoretically any stage could
Name the antiviral: Guanosine analog, takes advantage of thymidine kinase (TK) and DNA polymerase to inhibit viral replication
Acyclovir
What virus? Non-enveloped icosahedral capsid, Double stranded circular DNA, Replicates in the nucleus
Human papillomavirus (HPV)
T or F: Genital warts and non-genital warts are the same type of HPV
False; they differ
How is HPV transmitted?
contact
What could happen if you just so happen to ACCIDENTALLY aspirate cervico-vaginal secretions infected with HPV?
Laryngeal disease
What is the incubation period for HPV?
3 months to years
T or F: HPV can be treated with antivirals
FALSE
Which serotypes of cervical cancer are caused by HPV?
16 and 18
What oral manifestations can HPV have?
oral benign epithelial tumors
What virus? Icosahedral capsid, enveloped, positive single-stranded RNA, Acquire envelope by budding into intracellular vesicles, not at the cell surface
Hepatitis C Virus (HCV)
What is the #1 cause of liver transplantations in the US?
HCV
There are how many people infected w/ HCV in the US?
4 million (1 in 70-100) Numbers baby.
How is HCV transmitted?
blood (ie needlesticks)
T or F: HCV can be asymptomatic
TRUE
What 3 types of disease can HCV cause?
Acute (15%), Chronic (70%, 20-40% progress to cirrhosis & liver failure), Rapid cirrhosis (15%) (5% develop cancer after 30 years)
T or F: HCV can be managed by antivirals.
FALSE
T or F: There is no vaccine for HCV.
TRUE
What can you use to treat HCV?
Interferon alpha, and ribavarin
What virus? Helical, single strand positive RNA, enveloped
Coronavirus
What virus is associated with SARS?
coronavirus
T or F: SARS virus is localized to upper respiratory tract
TRUE
What is SARS-CoV?
a coronavirus
How are coronaviruses (SARS) spread?
Aerosols and large droplets
What is the first symptom of SARS?
High fever (> 100.4 F), then headaches, discomfort, body aches
As a symptom of SARS, about 10-20% of people also have ________.
diarrhea cha cha cha
T or F: Most SARS patients normally develop pneumonia.
TRUE
T or F: There are antivirals that effectively treat SARS.
FALSE
What Virus? Positive single-stranded RNA (diploid), Icosahedral capsid, Enveloped, Reverse Transcriptase (RT): RNA-dependent DNA polymerase
HIV
Regarding HIV infection, what is the purpose of the GENOMIC RNA?
To serve as a template for the synthesis of viral DNA
What primary infection results in mononucleosis-like syndrome?
HIV
What effect does the initial immune response have on HIV infection?
Restricts viral infection but contributes to pathogenesis
What is the terminal stage of an HIV infection?
AIDS
How is HIV transmitted? (think magic johnson and Paul)
Sex and blood

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