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