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146 Cards in this Set
- Front
- Back
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Explain why a virus is not living |
Viruses lack the ability to take up energy and make use of it, and transport and reproduce themselves. They are obligate parasites. |
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Define: Virion |
infectious viral particle containing all virus components |
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What are River's Postulates? (6) |
1. Isolation of virus from diseased hosts 2. Cultivation of virus in host cells 3. Proof of filterability (confirms small size) 4. Production of a comparable disease when used to infect experimental animals 5. Re-isolation of the same virus from the infected host 6. Detection of a specific immune response to the virus |
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What viruses can be detected by the fever they cause? |
Influenza and Yellow Fever |
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Why might a viral infection go undetected by heat scanners in airports? |
Viruses have incubation periods. Would not see a fever until the disease is established. |
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Advantages of having the viral genome packaged in a capsid? |
- protects the genetic information (resistant to proteases, heat or other temperature extremes) - mediates transmission from one host to the next
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How do the protein coats "know" how to assemble? |
SELF ASSEMBLY - the information for assembly is contained within the protein structure itself. |
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What are the 5 basic steps in the viral life cycle? |
1. Attachment - using a variety of receptors 2. Penetration - crossing the membrane 3. Utilization - host cell proteins/enzymes for transcription, translation and replication 4. Biosynthesis - synthesis of proteins 5. Assembly - progeny particles are produced
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What is the difference in the life cycles between enveloped vs. naked viruses? |
The viral envelope membrane fuses with the host cell membrane to allow entry, and the virus then leaves by budding off and taking some host membrane with it. |
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How does the membrane help the virus hide from our immune system? |
- it is of host origin - contains host proteins |
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Explain the lag and exponential growth phases in viral life cycles |
- at first there is no sign of infection as the virus is replicating itself, but then they tend to release a large number of particles within 24 hours. |
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Describe the process of determining viral titre |
- dilute bateria with melted agar - pour onto agar plate - phage plaques make 'holes in lawn' - performing subsequent dilutions will allow you to get a nice number of plaques to count (don't want too many or too few)
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What is the virus titre reported as (concentration units)? |
plaque forming units/mL |
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What are the three criteria used to classify viruses? |
1. nature of genetic material 2. symmetry of the capsid 3. presence of an envelope, dimensions
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What are three criteria for initiating a viral infection? |
1. sufficient virus at site of entry 2. host cells must be susceptible and permissive -susceptible: have receptors for entry -permissive: have replication and dissemination of the virus 3. Local antiviral defense must be breached |
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Define: Pandemic |
worldwide epidemic |
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What are the characteristics of an acute infection? |
rapid and self limiting |
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What is the critical part of the immune response for an acute infection? |
innate immune response. Must get the viral infection under control before it starts to replicate. |
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Explain the two types of infections Hepatitis B (HBV) can cause and how it is transmitted |
1. Acute (90-95%) - fever, loss of appetite, and other flu like symptoms 2. Persistent (5-10% of adults and 95% of babies that are infected perinatally) - permanent liver damage of liver cancer
Transmitted via infected blood |
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Why is it an advantage for a virus to have a persistent lifestyle? |
It has a host for 60-70 years |
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Explain how acute, persistent and latent infections are different |
Acute: virus hits hard and fast and then is absent in the infected person Persistant: virus titre is consistently high Latent: Extreme persistant infection (like herpes simplex virus) symptoms come and go
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What type(s) of infection(s) do(es) measles cause and what are the complications? |
Generally measles is an acute infection but a small number of people will get SSPE (subacute sclerosing panencephalitis) which a latent form that causes a brain infection and then death. |
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3 Types of Injury Caused by Viruses |
1. Cytopathic effects on cells directly (lysis) 2. Oncogenic (lose contact inhibition and and their normal interactions and become immortal, transformation of viral genes into hist genome or viral disruption of host genes) 3. immunopathology (damage as a result of local inflammation) |
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Explain how viral oncogenes cause cancer |
Retroviruses can take up cellular DNA and they integrate a provirus form into the genome. If this integration was to occur in a gene that encodes for regulation of cell cycle then this could cause cancer. |
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Explain the example of rous sarcoma and the src gene and how these cause cancer |
Rous sarcoma virus has taken up a SRC gene, called v-src to distinguish it from cellular src. Src is a cell signalling molecule that phosphorylates proteins involved in signal transduction. When the protein is missing the C terminal tail, phosphorylation is always happening because the active site is always available (C term usually has to undergo a conformational change to uncover the active site) and therefore the cell undergoes constant proliferation. |
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Define: cytopathic effect |
structural changes in host cells caused by viral invasion |
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What are two things that happen to cancer cells that are visible under a microscope? |
Loss of contact inhibition (cells normally do not pile up on each other) Anchorage independence (cancer cells lose their attachments to connective tissue and become mobile) |
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What are the 3 ways "stuff" can enter the cell? |
1. phagocytosis (big stuff) 2. pinocytosis (sugar/small stuff) 3. receptor mediated endocytosis (viruses) |
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What are the steps in receptor mediated endocytosis? |
1. ligand binds a cell surface receptor. This diffuses into an invagination coated with clathrin. 2. The clathrin pit pinches off forming a coated vesicle. 3. The clathrin unchaste the vesicle 4. vesicle fuses with the early endosome. (acidic) 5. the acidification releases the ligand from the receptor and the receptor is returned to the cell surface.
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What host cell receptors do poliovirus and rhinovirus utilize? |
poliovirus: PVR rhinovirus: Icam-1
Both glycoproteins must be human.
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Define: tropism |
cells and tissues of a host with support growth of a particular virus or bacteria. Presence of a certain receptor determines the specificity of host. |
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Explain the importance of the recessed binding site in Icam-1 |
Makes it very difficult to make antibodies that are able to get in |
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Why don't we mutate Icam-1 to inhibit HRV binding? |
rhinovirus interacts with the same domain that our LFA-1 and other proteins in our immune system |
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Explain Rhinovirus entry and uncoating |
the virus attaches to Icam-1 and enters by endocytosis. The acidic environment of the endosome causes the uncaring of the particle. The RNA is released into the cytoplasm.
Note: Rhinovirus is not acid resistant, unlike poliovirus.. this is why the acid will cause structural changes in Rhinovirus
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What does a neutralizing antibody do to the binding of Icam-1 |
The antibody blocks the canyon so Icam-1 can't bind |
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Explain how the entry of poliovirus into the cell is different than for rhinovirus |
The interactions with PVR cause major structural changes within the virus. Poliovirus is acid resistant so the acidic environment does not cause the changes that allow the RNA to escape like in rhinovirus. |
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Explain pore formation in the membrane by poliovirus |
Interaction with the PVR causes a major structural change. The N termini of the VP1 protein extends into the membrane. This may form a pore in which the RNA can enter. (PVR binds to VP1)
Fc receptor mediated internalization of poliovirus (by a macrophage for example) does not allow uncoating |
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Define: fusogens |
protein involved in fusing of viral membranes. It is very hydrophobic which aids in the binding of membranes. |
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What is the cellular receptor for influenza virus attachment? |
sialic acid at the ends of glycoproteins. Human influenza HA prefers to bind to an alpha (2,6) linked sialic acid (human linkages) |
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Explain influenza virus entry with the HA fusion |
1. initial attachment 2. conformational change in the HA receptor caused by lower pH 3. membranes pulled closer and closer together until they fuse (due to further structural changes in the protein)
HA works as a trimeric protein |
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What is the most common mode of transmission for HIV? |
Blood plasma. In 100% of patients, the virus could be isolated from blood plasma (only 3/55 samples could be isolated from saliva) |
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Explain when we see symptoms of HIV |
between 2-6 weeks the patient will show flu like symptoms, but then a long asymptomatic phase ensues and we don't see symptoms again until the immune cell concentration is 5/mL (the concentration slowly decreases over the asymptomatic phase). This is why HIV+ individuals generally die from very rare infections. |
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Why does HIV package reverse transcriptase in its caspid? |
The first thing it does in the host is to make a DNA copy of itself to insert into the host DNA. |
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Explain HIV fusion at the cell membrane |
1. The virus particle binds to CD4 and coreceptor (a chemokine, CCR5) on the T cell with its surface protein, gp120. 2. HIV gp120 binds CD4 and causes a conformational change that exposes the CCR5 receptor binding site. The binding to the co-receptor induces a second conformational change exposing the fusion peptide.
*HIV does not enter in an endosome, but at the cell membrane. Only one copy can enter the cell (interference). |
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Define: Interference (in regards to HIV) |
only one retrovirus can infect a cell |
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Explain the structure of the HIV-1 envelope glycoprotein |
gp120 - trimer with many variable regions and extensive glycosylation. The conserved regions are to bind to CD4. gp41 - fusogen. completely covered by gp120 and therefore hard to make antibodies to. |
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What types of cells are infected by HIV? |
HIV infects cells that have CD4 and chemokine receptor |
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Mutations in what gene enable HIV resistance? |
mutations in CCR5 genes (sex trade workers in Europe.. repeatedly exposed and have mutations) |
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Explain the process in which HIV is incorporated into the host genome |
Reverse transcriptase copies ssRNA into sDNA and then integrate inserts DNA into the genome. |
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Who discovered reverse transcriptase and how? |
Temin and Baltimore discovered that RNA can be converted back into DNA while looking for cancer causing viruses
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What is the mechanism of converting RNA to DNA? |
1. Reverse transcriptase creates one full DNA strand 2. RNase H cute RNA attached to the DNA 3. DNA pol creates other strand (polypurine tracts, PPTs, serve as primer for second strand) |
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Explain why quasi species arise from HIV integration into the host genome |
Reverse transcriptase is very error prone so all copies will have different mutations, making them slightly different.
*Both deletions and insertions arise when slippage occurs. |
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Explain why cells infected with HIV must be activated for the virus to replicate? |
Transcription factor NFKB is turned on by the activation of infected T cells or macrophages |
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Explain the assembly of new viral genomes |
1. Tat amplifies transcription of viral RNA. Rev increases transport of singly spliced or unspliced viral RNA to cytoplasm. 2. the late proteins Gag, Pol, and Env are translated and assembled into virus particles which bud from the cell. |
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List the HIV genes and their function |
gag (group specific antigen) - core proteins and matrix proteins pol (polymerase) - reverse transcriptase, protease, and integrase enzymes env (envelope) - transmembrane glycoproteins. gp120 and gp41 tat (transactivator) - positive regulator of transcription rev (regulator of viral expression) - allows export of unsliced and partially spliced transcripts from nucleus vif (viral infectivity) - affects particle infectivity vpr (viral protein R) - transport of DNA to nucleus. Augments vision production. Cell cycle arrest. vpu (viral protein U) - prmotes intracellular degradation of CD4 and enhances release of virus from cell membrane nef (negative regulation factor) - augments viral replication in vivo and in vitro. down regulates CD4 and MHC class 1. |
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What is the Baltimore Classification based on? |
how many steps from the original form of the virus until mRNA |
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(+) strand RNA viruses |
can synthesize their own polymerases and don't need to package it with the RNA |
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Why does a positive strand virus make (-) strands? |
as templates to make more (+) strands |
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What are the structural capsid proteins of poliovirus? |
60 copies of the four proteins, VP1, VP2 VP3 and VP4. VP1-3 are involved in the binding to gp120 and VP4 is for structural support. |
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Explain the reproductive life cycle of poliovirus |
1. genetic material inserted into cell 2. RNA associates with ribosomes 3. translation 4. polyprotein is made 5. polyprotein cleavage (first cut by auto cleavage) 6. RNA synthesis occurs on vesicle membranes 7. (+) strand moves to vesicle 8. (-) strands are made 9. (+) strands are made from (-) strand 10. Cleavage of capsid precursors 11. Assembly 12. Exit via lysis |
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Explain what happens to the polyprotein in poliovirus |
1. Autocleavage (rate limiting step) 2. Virally encoded proteases (2Apro and 3Cpro) cut out the rest of the viral proteins
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What is CDpol? |
RNA dependent RNA polymerase (uses RNA to make RNA) Specific to viral RNa (doesn't see ours) Makes several mistakes every replication (producing quasi species)
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How does the 3Dpol polymerase tell which RNA is viral and which is host? |
The polymerase is recognizes the secondary structures of viral RNA and not ours (based on sequence) |
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Explain the protein primer in poliovirus replication |
1. 3AB (VPg precursor.. 3C cleavage of 3AB forms VPg-RNA) takes RNA to the membrane. 2. The RNA strand links to 3AB via a tyrosine. The tyrosine initiates the RNA (nucleophilic attack to attach UTP to protein) 3. Primer starts synthesis on the tyrosine of 3AB. 4. Elongation 5. Cleavage of VPg off 3AB
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What is the signal for the RNA genomes to be packaged? |
high concentration of capsid precursor outside of the nucleus (or cell??) |
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Explain template exchange in poliovirus recombination |
When the RNA polymerase is replicating the template, it will often 'hop' to another strand to finish replication. This can occur when it gets to something that doesn't look like self, so by jumping it can make one correct copy of itself. |
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How is an attenuated virus made? |
Serial Passage (passed through non-human cell lines)
1. pathogenic virus isolated from patient 2. culture virus and infect monkey cells 3. virus acquires many mutations allowing it to live well in monkeys 4. virus no longer grows well in human cells and may be a candidate for a vaccine
Reversion is possible and some mutations may not affect the infectiousness of the virus in human cells |
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Why does Canada use an attenuated poliovirus in their vaccinations? |
poses no risk of mutations back to the infectious form |
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A virus is more likely to encode their own enzymes if it is ________________ |
larger. |
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What is the structure and genome organization of herpesvirus? |
enveloped virus with linear dsDNA. |
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Common Mechanisms in exponential viral DNA replication |
1. template directed (can't really do this because most host cells are in the G0 stage of cell cycle. Nucleotides are not readily available 2. Each strand is copied at the beginning at the origins 3. Uses a DNA dependent DNA polymerase
* 2 & 3 require cell to be in S phase because generation of dNTP for DNA synthesis only present in S phase
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What are some properties of the replicons in mammalian and viral DNA? |
-AT rich DNA sequences allow the dsDNA to breathe a little (weaker section due to 2 hydrogen bonds between these base pairs) -Bidirectional replication from an origin
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What does primase do? |
RNA synthesis of primers on the ssDNA opened at replication fork. Lagging strand needs many of these primers but the leading strand only needs one at the very start of replication.
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What is "the end problem" with replication of linear DNA? |
with each round of replication, the lagging strand would get shorter and shorter due to the lack of primer for the DNA pol to grab onto. In mammals, telomerases deal with this problem by extending the 5' end of the template strand. |
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Explain the rolling circle mechanism of DNA replication |
*1st step in replication of herpesvirus is to circularize the DNA, then this process can happen
1. Knick in one strand 2. replicated by continuous copying 3. displace the strand 4. complete the lagging strand (on the displaced leading strand) 5. double strand DNA templates result 6. Keep making more copies by continuing around again
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Define: concatemers |
end to end genomes |
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Explain the packaging of herpesvirus into the capsid |
1. Proteins bind to specific sequences at ends of the genomes in the concatemer 2. empty capsid binds to these proteins 3. a headful of DNA is stuffed in until the proteins on the other side of the genome are reached. 4. DNA cleavage |
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Why do viruses that utilize host replication machinery tend to mutate less? |
The host polymerase generally will proofread for the virus, but often the viral polymerases will not have any proofreading abilities. |
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Explain the reproductive cycle of herpes simplex type 1 |
1. DNA inserted 2. DNA goes into nucleus and is circularized 3. (+) strand RNA synthesized and sent into cytoplasm for protein synthesis 4. Different stages of protein synthesis (immediate early, early and late) 5. Concatemer made and proteins bind to each side of the genomes 6. Capsid proteins from the late stage sent to nucleus where they are stuffed full of viral DNA 7. Exit the cell via exocytosis like mechanism
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Explain how herpes simplex latent infection works |
occurs primarily in neurons (i.e. nerve by mouth). transcripts are produced from parts of the genome to produce proteins required to maintain latency. |
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How does the virus make sure that an RNA genome gets in every virion? |
the capsid proteins auto assemble in a concerted assembly with RNA. RNA performs the final protein cleavage of the capsid from inside (VP2 and VP4). RNA acts as a ribozyme. |
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What is the purpose of packaging integrate and reverse transcriptase into the virion? |
So it can make copies of itself by inserting into the host genome before it makes viral proteins |
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Where do the membrane proteins gp120 and gp41 get made? |
In the RER. |
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Where does the assembly of most enveloped viruses take place? |
at the plasma membrane |
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Why is the innate immune system so important in a viral infection? |
It keeps the viral titre at bay (or slows the replication) until the adaptive immune system kicks in. They are the most important in an acute infection. |
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What molecule from the innate immune system recognizes the viruses? |
TLRs recognize viral capsids and viral DNA/RNA.
RNA- TLR3&7 DNA- TLR9
Recognition of danger is often through the detection of tissue damage. |
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How do neutrophils deal with virus infected cells? |
Defensins, on cells such as neutrophils, are secreted and are antivirals that bind to the capsid of a virus to inhibit assembly. Other antivirals will cause a virus infected cell to lyse, which causes tissue damage. (i.e. alpha defensin) |
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How do macrophages deal with virus infected cells? |
TLRs recognize viruses from their DNA/RNA or their surface glycoproteins.
Steps: 1. internalize antigen 2. detection by endosomal TLR receptors 3. Deliver signals into the cell to activate macrophages 4. Release cytokines to initiate immune responses (ie proinflammatory cytokines such as TNF-alpha, IL-1 and IL-6).
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What are the effects of pro inflammatory cytokines? |
- Act on the hypothalamus causing fever - colony stimulating factors act on bone marrow to increase WBC output - Acute phase proteins are made by the liver 100-1000 fold up regulation (proteins such as mannan-binding lectin which binds to mannose and other non specific virus binding proteins)
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What is Mannan-binding lectin (MBL)? |
A proinflammatory cytokine that binds to mannose on viral glycoproteins and acts as an opsonin. |
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What is the significance of the terminal galactose-alpha(1,3)-galactose on viral glycoproteins that infect animals and not humans? |
We do not have an enzyme that breaks these bonds and therefore we make antibodies to this bond. This is why we don't generally get animal viruses. |
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What type of cytokines are the best type of response against viruses? |
Interferons. IFN-alpha and beta are type 1 interferons and are the major antivirals. INF-gamma is type 2 |
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Give the producer cells and inducers of IFN-alpha, beta and gamma |
IFN-alpha: - Leukocytes - virus infection, dsRNA
IFN-beta: - Fibroblasts, epithelial cells - Virus infection, dsRNA
IFN-gamma: - T cells, NK cells - Antigens, mitogens, Il-2 Il-12
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Explain how cooperation in the innate immune system amplifies the immune response |
Activated natural killer cells or T cells make IFN-gamma which activates macrophages. Macrophages then make TNF-alpha which activates NK cells.
Constant positive feedback between the two cells amplifies the immune response.
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What is the main purpose of interferons? |
They are cytokines ("warning proteins") made after the detection of ssRNA, dsRNA or viral capsid proteins. They bind to the receptors on other cells and turns on the antiviral program. |
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What occurs in the cells when the antiviral state is induced by interferons? |
1. induce resistance to viral replication in all cells. - 2'-5' oligoadenylate synthetase is activated which activates RNaseL - RNase L degrades cellular and viral mRNA - dsRNA activated protein kinase stop protein synthesis 2. increase MHC class 1 expression and antigen presentation in all cells 3. activate NK cells to kill virus infected cells
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What are the differences between the contemporary strain the influenza virus and the 1918 flu? |
Contemporary: - limited virus replication and dissemination - activation of normal innate immune response - interferons only activated for a short period of time - few or mind clinical symptoms
1918 Pandemic Strain: - wide dissemination and high/rapid replication - activated of overactive innate immune response - persistant activation of pro inflammatory cytokine and chemokine response - severe clinical symptoms (decreased lung function, acute respiratory distress syndrome, severe tissue damage, haemorrhaging, often fatal) |
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What is the benefit of a CTL killing an infected cell via induced apoptosis? |
The death of the infected cell is very contained and the apoptotic bodies are taken up by macrophages. We never have total rupture of the cell.
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How do CTLs recognize infected cells? |
CTLs recognize viral peptides presented on MHC class 1 molecules. The peptides they present are newly synthesized proteins in the cell. |
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What happens if the MHC 1 molecules we have don't recognize any of the viral peptides? |
We cannot get rid of the virus in that cell because the MHC will not present any of the peptides. |
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Why can one type of MHC molecule bind many different non-self proteins? |
The peptides must have the same anchor residues that bind the peptide to the MHC protein. On average 1-2 peptides from a virus will actually fit onto an MCH and create an immune response. |
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Explain CTL activation with IL-2 |
A naive lymphocyte is activated by the Class 1 MHC presenting antigen and the costimulatory signal. The proliferation and differentiation of the T cell is induced by IL-2.
*an activated T cell has more cytoplasm, and only lives for about a week. |
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Explain Helper T Cell Activation |
Same as for CTLs, but the cell is activated with the viral peptide presented on MHC2 molecules and the co-stimulator factor. These cells then start producing IL-2, which activates the CTLs |
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How does a CTL become a memory cell? |
If they activate themselves and cause differentiation with IL-2, they are not able to become memory cells, only effector cells. Only if a CTL gets its IL-2 from a T Helper cell it can go on to become a memory cell.
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Why are CTLs considered serial killers? |
CTLs are not damaged in the killing process, so they can kill numerous times (only release granules each time.. can produce more) |
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Explain the process in which a NK cell "decides" to kill a cell |
If the NK cell does not get the inhibitory MHC1 signal, then it kills the cell. Viruses often try and down regulate the expression of MHC class 1 on the surface so that they can hide from CD8 T cells, but this makes them targets for NK cells. |
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Why is a vaccine with a live attenuated virus much more effective than an inactivated heat-killed protein vaccine? |
the attenuated virus is a much better vaccine because you will initiate an infectious cycle which will produce memory cells. |
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What are nosodes and do they work? |
supposedly, they are fluid/tissues from infected patient that are diluted until there's nothing left. water takes on the shape of the virus.
They do not work because they have essentially 0 viral particles in them and are just a sugar pill. No antibodies produced. |
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What is the difference between monoclonal antibodies and polyclonal antisera? |
Monoclonal antibodies have on specificity whereas polyclonal antisera has many specificities. circulating antibodies are polyclonal. |
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What is a neutralization assay? |
an in vitro test in which antibodies bind to virus an prevent the infectious cycle. Generally this is done with a monoclonal antibody or polyclonal antisera from a vaccinated person, or someone who has survived an infection. |
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What are the three possible mechanisms of neutralizing antibodies? |
1. Steric interference with receptor 2. Fix capsid so pH dependent uncoating is blocked 3. Capsid stabilization so that uncoating is blocked |
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How does HIV survive in the face of an active immune system? |
many antibodies are useless, and it can mutate away from good neutralizing antibodies so they stop working. |
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What does a Western Blot help you identify? |
If virus is present in the sample, the sample will contain viral peptides that IgG can bind to and this will show up on the western blot. Can help us identify an HIV+ patient.
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What is the significance of B12 neutralizing antibody? |
It fits snugly into the binding site of gp120 so it blocks the virus from docking to CCR5 and CD4 |
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Why do most antibodies fail? (3) |
1. variable regions cover the conserved regions of the protein. This makes it so that we make antibodies to parts of the protein that can change. 2. The two receptor mechanism is an evasion strategy because the important surface proteins are hidden until right before the moment of fusion. (there is a 32 bp deletion in some places in the world) 3. Molecular mimicry (looks like self). part of gp120 is shaped like the chemokine RANTES that binds to the CCR5 receptor. |
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How could the host prevent HIV entry? |
mutations in CCR5 |
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Why would polyclonal antisera work better to defeat HIV than a monoclonal antibody? |
having one part of the gp120 can completely change without causing the virus much stress, but a polyclonal antibody puts a lot of stress on the virus |
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What is the evolving glycol shield in HIV? |
HIV mutates its gp120 by changing the glycosylation sites so that the variable regions will change without affecting the conserved region of the protein. |
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What are the four antibody responses to HIV? |
1. NEUTRALIZING. Neutralizing antibodies block the fusion process 2. ENHANCING Low affinity antibodies binding to complement or Fc receptors can help HIV get in and it can escape and infect this cell 3. AUTOIMMUNITY. Molecular mimicry. regions of gp120 look like self and antibodies are not made 4. INTERFERING. interfering antibodies bind to HIV but do not block entry, but lock the action of neutralizing antibodies. |
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Why is a second infection by Dengue virus worse? |
the antibodies from the primary infection cannot neutralize the virus. Instead, the Ab-virus complex attaches to receptors called Fcy receptors on circulating monocytes. The antibodies help the virus infect monocytes more efficiently. This increases the overall replication of the virus and a higher risk of severe dengue. |
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What is HAART? |
Highly active antiretroviral therapy: - combination of 3 or more antiviral drugs
2 kinds of nucleoside RT inhibitors: - AZT and 3-TC (once phosphorylated, AZT has a higher selectivity for the viral RT, and no 3' OH on the DNA chain = termination of chain)
protease inhibitor: - darunavir - binds and blocks active site of the HIV protease. - extensive H-bonding
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What are the pros and cons of HAART? |
pros: - >90% viral suppression - viral suppression prolonged a lot longer than if you used only one drug - increased life span of patient
cons: - doesn't work for everyone - serious side effects - expensive - 35 pills at precise times
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Explain how Dendritic Cells (DCs) activate naive cytotoxic T cells |
DCs express MHC 1 and also express high levels of B7 (a costimulator for CD8 T cells). Activated CD8 T cells make IL-2, driving its own proliferation and differentiation. |
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Why do HIV infected individuals have 80% of the CTLs remaining immature and why is this a bad thing for the killing of HIV? |
The CTLs are not getting enough IL-2 from TH cells. This is bad because the cells do not have granzymes and perforin needed for killing. |
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What are nascent proteins? |
a protein created by a ribosome before it forms into its final shape |
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In humans, how are the MHC class 1 (HLA) genes expressed? |
co-dominantly (we have 6 altogether) |
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Explain the epitopes that are able to be bound to MHC 1 proteins |
linear 9 amino acid sequence from within the protein. Viral peptides can be presented if they have the right anchor amino acids (the other residues don't matter for binding). |
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What are HIVs response to both ineffective and effective CTLs? |
ineffective: - conservation or no selection
effective: - selection of escape mutants - some people will show no selection or slow selection of these mutants which means that they most likely can combat this virus (the lucky people)
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Explain how HIV defeats our immune system by avoiding being presented on MHC 1 molecules |
It will change one or both of the anchor residues to any other amino acid. |
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Define: immunodominant epitopes |
CTL immune response tends to focus on a few epitopes originally seen. Sometimes called "original antigenic sin" |
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Which epitopes of MHC 1 are easy to change? |
HLA-A3 (bound epitope of Nef protein) HLA-B8 (dominant epitope of Nef protein |
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What epitope of MHC 1 progressed slowly to disease? |
HLA-B27 (has to mutate two amino acids to escape) |
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What epitope of MHC 1 is impossible to change? |
HLA-B57 (long term non progressives. All individuals have normal CD4 counts, low viral concentrations an don symptoms of AIDS) |
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What is Nef? |
Nef is viral protein that causes MHCs to go into endosomes and be recycled. (Down modulating surface expression of MHC). It only attacks HLA-A and HLA-B. This means that it leaves HLA-C on the surface which is the protein responsible for NK recognition. This prevent NK cell attack. This is because it targets the sequences in the tail of A and B, C does not have the target sequence. |
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How does poliovirus down modulate surface expression of MHC? |
Poliovirus interferes with protein transport in the cell to make vacuoles. Any new vesicles budding off from the ER never make it to the membrane. No new surface proteins, such as MHC, make it to the membrane. |
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Define Zoonosis |
transfer of a pathogen from non-human animals to humans and subsequent spread of the pathogen between humans |
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How did HIV transfer to humans? |
HIV was transferred from infected primates. It is though that it jumped more than once (3 times) in three separate cases for HIV-1 and once for HIV-2. |
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How can you prove which virus is the infectious agent in a patient or group of patients with the same symptoms? |
Find the virus in the majority of the patients or antibodies to it. Replicate it in an animal host if possible. |
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Explain SARS |
- a coronavirus - host = fruit bat - (+) strand RNA virus - Genome 30kb - Enveloped |
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Explain MERS |
- new coronavirus - prevalent in Saudi Arabia |
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What must (-) strand RNA viruses always package within their virion? |
RNA-dependent RNA polymerase. Otherwise, the viral proteins could not be made. |
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What is Ebola? |
- virus that causes hemorrhagic fevers - larger than average virus (worm looking) - still very relevant in Sierra Leone and Guinea - transmission is via bodily fluids |
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How are influenzas named? |
H stands for hemagglutinin N stands for neuraminidase
The number after the letter signifies the type |
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What made the 1918 flu so deadly? |
suppressed interferon response to the virus. It down regulates cytokine production. |
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What is H5N1? |
- March 7, 2003 - Avian flu - virus was deadly in poultry and humans. - direct contact transmission - completely shuts down the interferon response. - Tigers and leopards in zoos were being fed infected poultry and becoming sick
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Explain the 2009 flu pandemic in Canada |
An infected Alberta farm worker returned from Mexico, infected his pigs, who infected the health workers, and it spread from there. |
