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164 Cards in this Set
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Parvoviridae: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Parvoviridae are all ssDNA viruses that are nonenveloped which is part of the reason they are so resilient to things like stomach acid and disinfectants. |
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What does CPV stand for? What does FPV stand for? |
Canine Parvovirus Feline Panleukopenia Virus |
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Where in the host cells do parvoviruses replicate? |
Entry = Receptor-mediatedendocytosis Replication/Assembly = Nucleus (since they are ssDNA viruses) Release = Cytolysis |
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What two systems does parvovirus typically attack in adult animals (both cats and dogs)? |
Digestive System and Hematopoietic System. Resulting in the destruction of crypt cells and lymphoid cells (both of which are rapidly multiplying cells). |
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What specific pathological effect/lesion do you see in young cats that are affected by parvovirus between the two weeks prior to birth and the two weeks following birth? |
Cerebellar Hypoplasia due to the pantropic effects of Parvovirus in fetuses and neonates |
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Feline Panleukopenia is due to what family of viruses? |
Parvoviridae |
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How is FPV transmitted? |
It is shed in all bodily secretions! That means saliva, feces, blood (arthropods), through placenta to fetus. So both vertical and horizontal transmission. |
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What is the most common viral disease in dogs? (think about which one you heard about most before coming to school)
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Canine Parvovirus |
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What specific pathological effect/lesion do you see in puppies that are infected with parvovirus? |
Myocarditis - typically leading to sudden death due to heart failure or at least permanent scarring. (Notice the necrotic, white areas in the myocardium) |
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How do you test for a parvovirus infection in-house? |
SNAP test |
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What is PPV? |
Porcine Parvovirus (the most common/important cause of infectious infertility) Multiplies normally in the intestine of the pig without causing clinical signs. |
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QUIZ QUESTION! What will be the CPE from a parvovirus infection? |
1) Intranuclear inclusion bodies: makes sense since they are ssDNA viruses and are replicating in the nucleus 2) Cytolysis: makes sense because the way the virus exits the cell is by lysing it |
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QUIZ QUESTION! What general type of cell does the parvovirus infect? |
Rapidly dividing cells (S phase) That is why it targets the crypt cells in the gastrointestinal system and the myeloid and lymphoid cells in the hematopoeitic system |
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QUIZ QUESTION! What is the difference between FPV and CPV? |
They are very similar but the binding proteins on the surface of the virus are different (thats why FPV doesn't infect dogs and visa versa) FPV can cause cerebellar hypoplasia in kittens. CPV can cause myocarditis in puppies. |
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QUIZ QUESTION!
What is common between PPV and CPV? |
Morphology, Replication, Genome! |
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Where does coronavirus get its name? |
Corona = "garland or crown" It looks like a crown! The spike proteins in the surrounding envelope radiate out. |
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Coronaviridae: ss or ds? DNA or RNA? enveloped or nonenveloped? (think about the name of the virus for a hint) |
Coronaviridae are all +ssRNA viruses that are enveloped and that are classically identified by their surrounding spike glycoproteins. |
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CLASS QUESTION! Which viral protein of the coronavirus is the major antigen? |
Spike Glycoproteins (labeled S in the image) |
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Coronavirus belongs to the Order Nidovirales, which are the "Nested" Viruses. What does that mean? |
It means they have a nested set of mRNAs that are generated in the following manner: 1) The +ssRNA is used to form the -ve transcript 2) That is then transcribed into monocistronic mRNAs of different sizes. The nested set of RNA is the most efficient form of control. |
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What are the four groups of coronaviruses? |
*Group 1 (Alpha) - canine coronavirus, feline coronavirus, human coronavirus Group 2 (Beta) - bovine coronavirus, human coronavirus, murine hepatitis virus Group 3 (Gamma) - infectious bronchitis virus, pheasant coronavirus, turkey coronavirus Group 4 (Delta) - ... |
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Coronavirus causes what types of infections in the different animal species? |
Across both mammals and birds it causes both respiratory and enteric infections |
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What does FECV stand for? |
Feline Enteric Coronavirus - Highly prevalent in domestic cats - Infection is often subclinical or characterized by transient, mild GI illness in kittens - Transmission is fecal-oral route - Mutation of FECV can result in feline infectious peritonitis (FIP), a highly fatal, multisystemic disease |
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Why is it so common for FECV to mutate into the FIP virus? |
FECV is an RNA virus and the error rate of RNA dependent RNA polymerase is 1 for every 10 base pairs (very high!). FECV only has 30bp so get an average of 3 mutations every time it replicates! |
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What cells do the FIP virus bind with that result in the pathologic signs? (What's the cell tropism?) Does that make sense with the two clinical forms of the disease? |
Circulating monocytes Yes, because the virus is attacking the cells that would deal with the effusion in the abdomen and thorax (wet form) and the classic pyogranuloma cells (dry form) |
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What are the two forms of FIP? |
1) Wet Form (classic) - peritoneal and pleural effusion. More aggressive form 2) Dry Form - pyogranuloma and necrosis of multiple organs. Less aggressive form |
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CLASS QUESTION! What do monocytes do that leads to leakage from the blood vessels? |
Basically, inflammatory cytokine release increases vascular permeability resulting in plasma leakage. 1) Coronavirus infects the monocytes in the bloodstream 2) Monocytes then release inflammatory cytokines 3) Cytokines upregulate endothelial adhesin expression 4) Infected monocytes stick to adhesins and leave vasculature (some plasma leaks out) 5) Monocyte differentiates into macrophages and secreted more pro-inflammatory cytokines 6) More immune cells leave vasculature resulting in pyogranuloma. |
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CLASS QUESTION! What are the cellular components of a pyogranuloma? |
Macrophages, neutrophils and lymphocytes |
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Should you vaccinate your cats against FIP? |
NO! Increases the chances of getting FIP. In order to get prevention use early weaning and then separation. |
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What disease does the coronavirus cause in cattle? |
Bovine Coronavirus Enteritis (aka Winter Dysentery) - acute, highly contagious GI disorder - dark, hemorrhagic diarrhea (due to endothelial damage) |
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What are the pig diseases that are caused by coronaviruses? |
Porcine Hemagglutinating Encephalomyelitis Porcine Transmissible Gastro-Enteritis (PTGE) Porcine Epidemic Diarrhea (PED) |
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QUIZ QUESTION! What type of tissue damage is associated with FIP infection? |
Immune-mediated tissue damage due to Ag-Ab complex formation |
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QUIZ QUESTION! How are the pyogranulomas formed during an FIP infection? |
The host is trying to resolve the infection using the immune cells but they are forming Ag-Ab complexes and doing more damage |
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QUIZ QUESTION! What is the difference between feline coronavirus (FECV) and FIP? |
FECV targets the epithelial cells of the GI and Respiratory track FIP (mutated FECV) targets monocytes in the bloodstream |
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QUIZ QUESTION! What is common between feline coronavirus and canine coronavirus? |
Genome, replication and morphology! Plus they both cause respiratory disease |
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What family of viruses is shown in this EM image? |
Adenoviridae (adenoviruses) |
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Adenovirus: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Adenoviruses are all dsDNA viruses that are nonenveloped and the virion is icosohedral in shape. Since they are nonenveloped they are very stable and can pass through the stomach acid unharmed. |
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CLASS QUESTION! Where does the adenovirus replicate inside the cell? (Think about whether it is a DNA or RNA virus) |
In the nucleus (its a dsDNA virus) |
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What is CAV-1? |
Canine Adenovirus Type 1 (Rhubarth's Disease) |
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What two forms of disease can a CAV-1 infection develop into? Which one is more important*? |
1) *Hepatic form - leads to hepatocellular and endothelial destruction 2) Immune complex form - resulting in blue eye (corneal edema), glomerulonephritis, and viruria |
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Severe infections involving CAV-1 typically occur in what stage of life? Younger, middleage, older? |
Puppies under 6 months of age are most affected |
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What can happen with puppies that are under 6 months of age that get infected with CAV-1? |
Peracute disease with no signs resulting in the death of the puppy within 3-4 hours. |
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What is "blue eye" and what viral infection can cause it? |
Blue eye is bilateral corneal opacity due to Ag-Ab complex related corneal edema that occurs in 25% of CAV-1 infections. It will usually disappears spontaneously and can also develop post-vaccination |
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Fox encephalitis can be caused by what viral infection? |
CAV-1 - disease is characterized by vasculitis with disseminated hemorrhages, often associated with intranuclear inclusions in endothelial cells, and minimal or absence of inflammation in the brain parenchyma |
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Canine Adenovirus Type 2 (CAV-2) is different from CAV-1 because it is a disease of the ______ system. |
Respiratory |
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What clinical signs are the same between CAV-1 and 2 and which are different? |
Same: fever, depression, corneal opacity Different: - CAV-1: hepatitis and necrosis. More severe! - CAV-2: respiratory necrosis |
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CLASS QUESTION! What diseases are associated with CAV-1 and CAV-2 infections? |
CAV-1: hepatitis* (more severe disease) CAV-2: laryngotracheitis (less severe disease) |
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Calicivirus: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Caliciviruses are all +ssRNA viruses that are nonenveloped and the virion is icosohedral in shape. |
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What is FCV? |
Feline Calicivirus |
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FCV infects the ________ and causes what symptoms? |
Feline calicivirus infects the upper respiratory tract resulting in: - sneezing - nasal discharge - coughing - fever |
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What is VS-FCV? |
Virulent Systemic Feline Calicivirus - much more severe form of the virus - mutated form of the normal FCV (+ssRNA so it makes sense that mutations are likely to occur) - additional signs: edema, jaundice, dysphonia, increased mortality rate |
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Herpesvirus: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Herpesviruses are all dsDNA viruses that are enveloped. They contain 11-13 different glycoproteins in their membrane which means they have a very wide tissue tropism. |
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What is thymidine kinase and how do herpesviruses use it as a virulence factor? |
Thymidine kinase (TK) is a virokine that accelerates new DNA synthesis by salvaging thymidine from degraded DNA into TTP (Its definitely important in new DNA synthesis because a TK deletion leads to avirulence) |
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What are the three subfamilies of herpesviruses? |
Alphaherpesvirinae (BHV-1, EHV-1,4, FHV, CHV) Betaherpesvirinae (CMV) Gammaherpesvirinae (malignant catarrhal fever virus) |
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What are the characteristics of the Alphaherpesvirinae subfamily? |
– Latency in sensory neurons (ex in trigeminal ganglion) – Grow rapidly – Lyses infected cells |
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What are the characteristics of the Betaherpesvirinae subfamily? |
– Latency in salivary glands, kidneys, lymphocytes – Cytomegaloviruses(large balloon-like cells) – Growslowly – Cell lysisdoes not occur until several days after infection |
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What are the characteristics of the Gammaherpesvirinae subfamily? |
– Latency in lymphoid cells (B and T cells) – Replicatein lymphoid tissues – Growslowly – Lymphoproliferativediseases, transform cells |
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What is CHV-1 and what are the clinical signs? |
Canine Herpesvirus (CHV-1) resulting in Canine hemorrhagic disease Its the leading cause of death in 1-3 week old puppies. Signs are the normal viral ones plus blindness, seizures, and sudden death (CNS) |
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What is FHV and what are the clinical signs? |
Feline Herpesvirus Clinical signs are acute URI, conjunctivitis and corneal ulcers. Diseases of latency* |
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CLASS QUESTION! What is a latent infection? What is a recurrent infection? |
Latent infections are when the viral genome is laying dormant (asymptomatic) within the host cells, and the animal is not infectious. Virions are not present! Recurrent infection occur due to some kind of stressor where a virus that was dormant is released and causes the lesions (symptomatic), and the animal is once again infectious. Virions are present! |
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What is EHV and what are the two most common strains? |
Equine Herpesvirus EHV-1 (abortions, respiratory, neurological) EHV-4 (respiratory) EHV-3 (genital lesions) important but not as common |
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EHV-1 causes respiratory disease like EHV-4 but also has other signs. What are they? |
- Respiratory disease - Abortions - Paresis (remember the beginning example case) - Neurological disease |
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CLASS QUESTION! Can you find the EHV-1 viral DNA in the trigeminal ganglion and the T cells of an animal that has recovered from an EHV-1 infection? |
Yes, because the viral DNA has been incorporated into the host genome. That is what makes herpes treatment so difficult. |
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Can you prevent herpes infections? |
Sometimes. There is a vaccine against EHV-1 but its strong humoral response is short-lived. Need to revaccinate every 6-12 months. BHV-1 also has a vaccine. |
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What is BHV-1? What diseases does it commonly lead to? |
Bovine Herpesvirus 1 Infectious bovine rhinotracheitis (IBR) Infectious pustular vulvovaginitis (IPV) Enzootic pneumonia (Shipping Fever Complex) (All are respiratory disease, IPV has a genital component as well) |
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What are some of the complications that can occur with BHV-1 infections? |
- Abortions - Shipping fever (M. haemolytica, P. multocida) - Encephalitis - Fatal disease in newborn calves |
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CLASS QUESTION! Where does BHV-1 become latent? |
Trigeminal Ganglion and PNS |
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What two diseases does BHV-2 causes? |
Bovine Herpesvirus type 2 causes bovine mammillitis and pseudo-lumpy skin disease |
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CLASS QUESTION! What samples should you take from the sick animal if you suspect the animal has a BHV-2 infection? |
- Scrape the lesions - Draw fluid from vesicle - Blood samples |
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QUIZ QUESTION! What type of tissue damage is associated with alphaherpesvirus infections? |
Cellular lysis is the biggest effect, and you can see its effects in the respiratory system, CNS, and genital tract. |
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QUIZ QUESTION! What is a latent infection? |
An infection where the viral genome remains dormant in the host cells until an immunosuppressive event causes the virus to be released and cause lesions. |
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QUIZ QUESTION! What is the difference between the eye diseases of FIP and FHV? |
FIP (coronavirus) causes the formation of immune complexes in the eye resulting in cloudiness (blue eye) FHV (herpes) causes conjunctivitis, keratitis, and corneal ulcers. |
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QUIZ QUESTION! What is common between FHV and EHVs? |
Genome, replication, morphology! |
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What two diseases do alphaherpesviruses cause in birds? |
Avian Infectious Laryngotracheitis - respiratory disease resulting in conjunctivitis, swollen sinuses and nasal discharge and Marek's Disease - which has two forms: nervous form (paralysis) and visceral form (lymphoid tumors) |
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What two betaherpesviruses should we be aware of? |
Porcine Cytomegalovirus (PCMV) and Elephant Endotheliotropic Herpesviruses |
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Gammaviruses cause what major disease in ruminants? |
Malignant Catarrhal Fever (OvHV-2 and CpHV-2) |
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What are the clinical signs of malignant catarrhal fever, and what is the mortality rate? |
Tropism: lymphoid tissue, URT epithelium, intestinal epithelium Clinical Signs: profuse nasal and ocular discharge, diarrhea, erosions on the tongue, peripheral corneal opacity Mortality Rate: 100% |
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CLASS QUESTION! What is the common disease associated with alphaherpesvirus infections in pregnant animals? |
Abortions |
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KEY POINTS ABOUT ALL HERPESVIRUSES!!! Tissue tropism: ? Diseases: ? Transmission: ? Alphaherpesvirus infection: ? Beta and Gammaherpesviruses: ? |
Latency and Reactivation!!! Tissue tropism: epithelial, endothelial, lymphoid, neuronal Diseases: Respiratory, Reproductive, Tumor, CNS Transmission: mucosal contact (nasal, oral, genital) Alphaherpesvirus infection: Cell lysis + Abortions Beta and Gammaherpesviruses: chronicinfection |
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Paramyxoviridae: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Paramyxoviridae are all -ssRNA viruses that are enveloped. Their nucleocapsids can be a variety of different shapes, and their genome is very short (6-10 genes). Rely on RNA Editing for variety. |
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What is RNA Editing and which order of viruses relies on it heavily in order to produce multiple proteins? |
RNA Editing occurs when RNA dependent RNA polymerase inserts extra residues into the mRNA sequence when it is being synthesized. Members of Mononegavirales (including Paramyxoviridae) use this technique. |
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Bovine Parainfluenza Virus 3 and Canine Parainfluenza Virus 2 both cause disease in the _____. |
Respiratory System BPIV-3 - infection of nasal musoca and can predispose animal to other respiratory diseases (ex shipping fever and coviral infection) CPIV-2 - infection results in mild respiratory disease, and possible CNS disease |
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CLASS QUESTION! What viruses have we learned about that can cause respiratory disease? |
Coronavirus Adenovirus Calicivirus Herpesvirus Parainfluenzavirus Influenza viruses |
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What is NDV? |
Newcastle Disease Virus - affects both domestic and wild birds - transmitted through direct contact or contaminated feed - three strain: velogenic* (viscerotropic), mesogenic, lentogenic |
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Which of the NDV strains is the most virulent? |
Exotic Velogenic (viscerotropic) Strain - Exotic Newcastle Disease (END) - mostly neurological signs - highly virulent - mortality rate ~100% - die within 24 hours with no prior signs |
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Fill in the blanks for NDV Infections using the following terms (viscerotropic, mesogenic, lentogenic) Neurotropic (CNS lesions): ______________ Pneumotropic (Resp lesions): ______________ Enterotropic (GI lesions): ______________ |
Neurotropic (CNS lesions): All 3 Strains Pneumotropic (Resp lesions) : Mesogenic and Lentogenic Enterotropic (GI lesions) : Viscerotropic |
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What is CDV? |
Canine Distemper Virus - highly contagious - incurable (unless caught very early) - often fatal - tropism: CNS, GI, Resp - transmission: airborne - forms: peracute, acute, subacute, late |
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What viral infection is often mistaken for a rabies infection? |
Canine Distemper Virus |
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The peracute form of canine distemper results in sudden death of the animal. What occurs with the acute form? |
– Severe leukopenia – GI: severe vomiting and diarrhea, anorexia – CNS: depression, tonic-clonic spasms – Respiratory: catarrh, conjunctivitis |
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CLASS QUESTION! What two viruses cause severe leukopenia and diarrhea in dogs? |
Canine Parvovirus and Canine Distemper Virus |
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What other odd lesion occurs with the late form of a CDV infection in dogs? |
Hard Pad Disease Hyperkeratosis of the foot pad and nose |
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CLASS QUESTION! What systems are affected by CDV and NDV infections? |
Canine Distemper and Newcastle Disease (Paramyxoviridae) - CNS - Respiratory - GI |
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CLASS QUESTION! What are the common clinical signs from CDV and NDV infections? |
Behavioral change (CNS effects) Coughing and nasal discharge (Resp effects) Diarrhea (GI effects) |
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CLASS QUESTION! What are the reservoir hosts for CDV and NDV? |
Wildlife! CDV: foxes, raccoons, coyotes, skunks... NDV: ducks, geese, parrots... |
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Orthomyxoviridae: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Orthomyxoviridae are all segmented -ssRNA viruses that are enveloped. Their nucleocapsids are helical. HA and NA are surface antigens that are used to organize them into specific categories. |
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CLASS QUESTION! What is HA? |
HA = hemagglutinin (glycoprotein), it binds to sialic acid in order to enter the host cell HA cleavage into HA1 + HA2 is essential for infectivity! |
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What is NA? |
NA = neuraminidase, allows for budding and release from the host cell |
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Where does replication occur for members of Orthomyxoviridae? |
Nucleus! Don't assume otherwise because its an RNA virus |
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CLASS QUESTION! What is the major antigen determinant of a Flu Virus? |
Hemagglutinin (HA) |
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Influenza viruses are classified into three different types. What are they and what are the three distinguishing components that separate them? |
Types A, B, and C (A and B both have 8 segments while C only has 7) Distinguished based on nucleocapsid (NP), M protein, and unique antigens. |
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CLASS QUESTION! What gene is type specific in influenza viruses? A. PB1 B. HA C. NA D. M |
D. Matrix protein |
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What are influenza virus subtypes based on? |
Different combinations of HA (hemaglutinin) and NA (neuraminidase) on the envelope |
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How many different HA subtypes are there for Influenza Type A? |
17 HA subtypes |
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How many different NA subtypes are there for Influenza Type A? |
10 NA subtypes |
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Which of the 17 HA subtypes and 10 NA subtypes are in influenza viruses that infect birds?
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ALL SUBTYPES EFFECT BIRDS |
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What does A/equine/Saskatoon/1/90(H3N8) mean? |
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Why do we have so many different strains of influenza? |
Antigen Drift |
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What is antigen drift? |
Amino acid mutations on the HA or NA genes (ex. H1 -> H1.1) Mainly to evade immune surveillance. If enough mutations occur then you can get the development of a new HA or NA subtype. |
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The majority of mutations happen where on the influenza viral genome? |
HA -> HA1 + HA2 |
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What do we suddenly have a new, deadly strain of influenza virus? |
Antigen Shift |
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What is antigen shift? |
Big changes in viral DNA where they essentially get a "new" HA or NA (ex. H1N1 -> H2N1) Host is infected by two different strains of influenza and they exchange genetic material during replication |
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There are two distinct subtypes of EIV (H7N7 and H3N8) and they both cause disease in which system? |
Equine Influenza is an acute, contagious respiratory disease |
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Besides the H1N2 and H3N2 subtypes of SIV, which other one is most widely known? |
Swine Flu subtype H1N1 - acute, contagious respiratory disease in pigs - can be transferred to humans - same strain as 1920 Spanish Flu |
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There is only one subtype of CIV and it is _____. What other species can be infected with that subtype, and does that make sense with how influenza got into the dog world? |
H3N8 is the only strain that infects dogs, and it is said to have entered the dog world through racing greyhounds being around horses. |
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How lethal is avian influenza to poultry? |
Highly lethal |
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What three criteria make up the definition of Highly Pathogenic Avian Influenza? |
Highly Pathogenic Avian Influenza (HPAI) 1) Any influenza strain that kills >6/8 chickens 2) Any H5 or H7 subtype 3) Any non-H5 or H7 subtype that grows in culture in the abscence of trypsin |
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CLASS QUESTION! Why do the HPAIstrains result in so many deaths? |
They die due to a major over reaction of the immunesystem |
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CLASS QUESTION! What is a proinflammatory cytokine and list some examples? |
A proinflammatory cytokine is a cytokine which promotes systemic inflammation. TNFa, IL-1, IL-2, IL-6 |
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The influenzavirus causes _______ of the immune system, whereas Newcastle disease virus causes _______ of the immune system. |
Overreaction, Suppression ts":{"sPYS |
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CLASS QUESTION! What are the rolesof PB1, PB2 and PA? |
They are the subunits of RNA dependent RNA polymerase (PA, PB1 and PB2) which is involved in both transcription and replication of the viral genome. - PB1 = RNA chain elongation - PB2 = transcription - PA = RNA replication |
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QUIZ QUESTION! Which gene is thesame between H5N1 avian flu and H7N7 equine flu? |
They are both Type A (so the same M protein and nucleocapsid) |
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QUIZ QUESTION! What is commonbetween avian flu and canine flu? |
Genome, morphology, and replication! Plus they are both Type A influenza viruses |
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What istransformation? |
The conversion of a normal host cell into an abnormal cell with uncontrolled cell growth. |
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What are the three common features of transformed cells? |
- No contact inhibition (normal cells will stop multiplying if they run out of space) - No dependence on exogenous growth factors (normal cells will stop growing if they don't get the correct stimuli) - No anchorage dependence |
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What are the twomain ways you can interrupt signaling pathways to create a tumor? |
1. Inhibit tumor suppressor genes “cutting the brakes” 2. Mutate protooncogenes (normal cell cyclestimulators) into oncogenes “gas pedal is stuck down” |
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CLASS QUESTION! What are oncogenes? |
They are mutated genes that stimulate the uncontrolled growth of cells. |
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What are the threetypes of oncogenes? |
1. Proto-oncogene – normal gene that can be mutated and become an oncogene 2. Cellular oncogene (c-onc) – cellular gene that gets altered into an oncogene 3. Viral oncogene (v-onc) – viral genes act as tumor inducers |
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CLASS QUESTION ! What areprotooncogenes? |
Normal cellular genes that code for proteins that help to regulate cell growth and differentiation |
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What do DNA tumorviruses do to the host cells in order to cause oncogenesis? |
1. Inactivate tumor suppressor genes (like p53 and pRb) 2. Inhibition of apoptosis |
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What do RNA tumorviruses do to the host cells in order to cause oncogenesis? |
They alter signal transduction pathways 1. Growth factor expression 2. Growth factor receptor expression 3. Cytoplasmic or membrane-bound kinases 4. Transcription factors |
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CLASS QUESTION! What are viraloncogenes? |
V-onc act as tumor inducers |
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What are the fiveclasses of viral oncogenes? |
1. Secreted growth factors (ex SIS) 2. Cell surface growth factor receptors (ex ERBB, FMS) 3. Components of intracellular signal transduction systems (ex the RAS family, ABL) 4. DNA-binding nuclear proteins including transcription factors (ex MYC, JUN) 5. Components of the network of cyclins, cyclin-dependent kinases, and kinase inhibitors that governprogress through the cell cycle (ex MDM2) |
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What is the general process of transformation by a DNA tumor virus? |
1. Virusinfects host cells 2. ViralDNA is integrated (randomly) in host chromosome 3. Viralgenes are transcribed and translated producing oncoproteins 4. Viral oncoproteins interfere with normal cell proteins controlling cell growth and proliferation |
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What are the two most common tumor suppressor proteins that the viral oncoproteins interfere with? |
p53 and pRb |
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Papilloma viruses obviously cause papillomas which are _______? |
Benign warts |
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Papilloma viruses are non-enveloped dsDNA viruses that cause tumors. The transcription and translation in the host cells produce what two worthwhile viral oncoproteins? What tumor suppressor proteins does each interfere with? |
E6 binds to and inactivates p53 E7 binds to Rb which leaves the normal cellular oncoprotein E2F free (unbound) and available to activate the cell replication cycle. (imaged) |
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Simian virus 40 (SV40) is commonly used in labs because it is a polyomavirus. What makes it special? |
It produces a large antigen that can interact with both p53 and Rb, which is used to immortalize cell lines |
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Which two of the previously discussed virus families can also cause tumors formation? |
Adenoviruses and Herpesviruses |
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CLASS QUESTION! What subfamilies of herpesviruses are possibly associated with tumors? |
Gammaherpesviruses |
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What are the three methods retroviruses use to produce tumors? |
1. Transducing retroviruses - introduce a v-onc gene into the host cell chromosome 2. Cis-activating retroviruses - lack a v-onc gene, but integrate viral DNA near the c-onc gene 3. Tran-activating retroviruses - contain gene that codes for a regulatory protein thatmay either increase transcription from the viral long terminal repeat orinterfere with the transcriptional control of specific cellular genes |
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How do transducing retroviruses work? |
Transducing retroviruses introduce their v-onc gene into the host cell chromosome. Example: vErb (viral epidermal growth factor receptor) gets produced when the v-onc is inserted. VErb is always activated even though it doesnt have a binding site, so it doesnt need the external stimulus |
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How do cis-activating retroviruses work? |
Cis-activating retroviruses lack their own v-onc gene, so they integrate their viral DNA near the c-onc gene and alter the transcription. |
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Oncogenic viruses can be put into two very general classes. The acute transforming viruses which are v-onc ___, and the slow transforming viruses which are v-onc ___. |
The acute transforming viruses which are v-onc+, and the slow transforming viruses which are v-onc-. (Acute brings their own, while slow use the cellular oncogenes) |
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CLASS QUESTION! What proteins do oncogenes encode? |
Oncogenes are important cell regulatory genes that encode for proteins that function in the signal transduction pathways controlling normal cell proliferation (e.g., src, ras, and raf). |
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Retroviridae: ss or ds? DNA or RNA? enveloped or nonenveloped? |
Retroviridae are all +ssRNA viruses that are enveloped. They have 2 +ssRNA genomes, 2 reverse transcriptases, and 2 tRNA primers. |
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Retroviruses are unique because their genomes go through three distinct forms. What are they? |
2 +ssRNA -> Linear dsDNA intermediate -> Integrated dsDNA provirus +ssRNA do not serve as mRNA, but are instead combined |
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What are the three groups of genes that make up the retroviral genome? |
1. Gag - matrix protein, capsid, nucleoproteins 2. Pol - reverse transcriptase, integrase, RNase H, protease Env - surface glycoprotein, transmembrane polyprotein |
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CLASS QUESTION! How does a retrovirus convert its genome from +RNA to cDNA? |
Reverse Transcritpase |
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What is integration and what enzyme is responsible for making it happen? |
Once the +ssRNA of a retrovirus is converted into linear dsDNA it is inserted into the host genome in a process catalyzed by the virus-encoded integrase (IN) |
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Fill in the enzymes blanks |
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CLASS QUESTION! Are retroviral genome infectious? |
No! If you just put the genome into a host cell it wont have any effect. It needs to have things like RT and integrase in order to be effective. |
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What are the two genuses of Retroviridae that we discussed? |
Gammaretrovirus (FeLV) Lentivirus (FIV, EIAV, HIV) |
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Are lentiviruses characteristically aggressive and quickly progressive or chronic and slowly progressing? |
Lente = slow They are chronic, slowly progressing viruses most of which are v-onc- |
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Arrange the retroviruses into either the oncogenic or lentivirus categories. FeLV, FIV, EIAV, Canine adenocarcinoma |
Oncogenic Retroviruses: Feline Leukemiavirus (FeLV) and Canine adenocarcinoma virus Lentiviruses: Feline Immunodeficiency Virus (FIV) and Equine Infectious Anemia Virus (EIAV) |
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Cats that are persistently infected with FeLV can develop what type of lesions? |
Tumors, due to the recombinant of FeLV with the host genome to form Feline Sarcoma Virus (FeSV) |
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What are the different subgroups of FeLV and what clinical signs are associated with them? |
FeLV-A - severe immunosuppression FeLV-B - neoplastic disease FeLV-C - server anemia |
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True of False. The host immune response to FeLV can control the infection, and will result in a latent infection. |
True, but if the animal develops excessive stress or immunosuppression then it can reactivate and cause problems |
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When performing a SNAP test for FeLV/FIV you are testing for the FeLV antigen _______ and the FIV antibody _______. |
When performing a SNAP test for FeLV/FIV you are testing for the FeLV antigen p27 and the FIV antibody gp120. |
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In general oncogenic retroviruses cause tumors and lentiviruses cause what? |
Immune suppression |
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What are some examples of lentiviruses? |
• Maedi/visnavirus • Caprine arthritis-encephalitis virus (CAEV) • Feline immunodeficiency viruses (FIV) • Equine infectious anemia virus (EIAV) |
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What are the common clinical signs of an FIV infection? |
• severe gingivitis, periodontitis (oral cavity disease) • runny nose, coughing (upper respiratory disease) • diarrhea (gastrointestinal disease) • pyoderma (skin disease) • behavioral changes (neurological disease) |
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True or False Horses can clear an EIAV infection and are then no longer considered reservoirs for the virus. |
FALSE, once a horse is infected by the equine infectious anemia virus it will always be a reservoir for spreading the disease. Plus its a retrovirus (lentivirus) so the viral DNA has been integrated into the host cells genome |
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What are the secondary effects of thrombocytopenia in EIA cases? |
Petechial hemorrhages and Edema |
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What diagnostic test is used to detect EIAV? |
Coggins Test (an AGID) |
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How is EIAV mainly transmitted? |
Biting insects (usually horse and deer flies) |
