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158 Cards in this Set
- Front
- Back
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Which viruses are the ones that have polyprotein function?
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Picornoviruses - like poliovirus and rhinovirus
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What is the name of the piece of the polyprotein (the protease part) that cleaves all the other
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3Cpro
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How are alphaviruses different than picornoviruses (they are all class I)?
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Alpha viruses are larger, surrouned by envelope. But they also first translate the main proteins needed for replication, then they replicate the plus strand into minus strand, then they take the minus strand template and make more plus strands AND some sub-genomic mRNA
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What is a member of the flaviruses, and how does it replicate?
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West nile - class I postive sense RNA --> enveloped, it replicates just like picornoviruses, but as a subgenomic componenet like alphaviruses
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What is included in coronaviruses?
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SARS, common cold viruses, etc.
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What is significant about cornoviruses being class 2 RNA relication?
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they are SO big...
the polymerase is made first, then IT goes back and makes a WHOLE minus strand copy. the minus strand template surives to make more full plus strands and MULTIPLE subgenomic mRNA (the big difference from class I) |
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What is the receptor for coronavirus in the lungs, (note this virus is CLASS II replication, not that it matters, just fyi)
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ACE-II receptor -- expressed in lungs, heart, kidney, GI
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Significant about minus strand RNA?
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It has the polymerase packaged in the virion
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Examples of minus strand RNA viruses?
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Rhabdovirus (rabies)
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The first step of positive RNA is translation, for minus strand its....
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transcription. It goes minus-plus-minus
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What viruses cause tumors?
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DNA viruses:
1) HPV -cervical cancer 2) herpes EBV - Burkitts lymphoma 3) Hep B - hapatocellular carcinoma RNA viruses: 1) HTLV-1: T cell leukemia 2) Hep C - hepatocellualr carcinoma |
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T/F - retroviruses are RNA viruses.
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True
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4 classes of oncogenes:
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1 - oncogenic growth factor that mimics other factors (rare)
2 - mutated receptors - becomes activated inappropriatley 3 - intracellualr transducers - dysregulate these RAS or PKC 4 - transcription factor - change expression these so you get transciripton of growth factor genes |
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Why do most retroviruses not cause transformation?
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b/c they insert into an incosequential part of the host genome
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How do non-acute transforming virsues cause tumors?
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THey do it slowly, via insertional mutagenesis
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What DNA tumor viruses function to block tumor suppressor pathways?
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ADenovirus
Papillomavirus Papovavirus |
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Muations in RB are implicate where?
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retinoblastoma
lung cancer breast cancer |
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What protein in HPV function to cause tumors?
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E7 sequester Rb
E6 sequesters p53 |
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How does the myc oncogene work?
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It disrputs Rb binding to E3F by oxerexpressing proteins that control Rb phophorylation (an indirect mech)
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What viruses only replicate locally?
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influenza
Rotovirus Papiloma |
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What viruses spread out of the initial replication site and infect other tissue?
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small pox, varicella, CMV, Hantavirus, Polio, Measles
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What PRR did we talk about?
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RIG-I - retinoic acid inducible gene, it recognizies non-self RNA possessing 5' triphosphate structure. MDA-5 does the same thing
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What recognizes picornoviral RNA? (like what receptor?)
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MDA-5
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What is the principle trigger for Type I interferon?
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dsRNA
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example of a segmented virus
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INflUENZA - segmented negative sense RNA virus that undergoes drifts and shifts
but also Rotovirus Hatavirus |
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Antigenic drift vs shift
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drift - accumulation of point mutations eventually yield a variant protein that is no longer recognized by antibody to the original
Shift - mya occur by reassortment of an entire ssRNA between human and animal virions infecting the same cell |
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What are some viruses that have inactivated or killed vaccines?
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inactivated poliovirus
influenza virus vaccine Hepatitis A vaccine Rabies vaccine |
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What are the family, subfamily, stuff we are concerned about?
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ssRNA RT
Family - Retroviridae Class - Lentivirinae Geni - 1) Deltavirus - HTLV1, which causes tropical spastic paraparasis and T cell leukemia lymphoma syndrome 2) Lentivirus - HIV1 and HIV2 |
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What do deltaretroviruses cause?
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These include HTLV, which causes tropical spastic paraparasis and T cell leukemia lymphoma syndrome
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Is HIV an enveloped virus?
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yes
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What helps bind the HIV virus to t cells?
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Well GP120 on virus envelope binds to CD4, CCR5 is a surface coreceptor, which has a cousin called CXCR4
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What actually gets pumped into nucleus with HIV?
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The dsDNA.... it was made double stranded by the host cells own DNA dep DNA pol....but first it had to be reverse transcribed INTO DNA
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What are GAG proteins?
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They help organize the HIV virus structural within the cell
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how many sexual encounters will actually transmit HIV (from infected person)
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1/500... incrased risk with skin breakage like ulcer from syphilis or herpes
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CD4 count indicates what?
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It's a INDIRECT refelction of immune competency
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What were the first antiretroviral drugs?
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NRTI
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What are the main NRTI?
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Tenofovir is commonly used
Zidovudine Abacavir Lamivudine Emtricitabine Stavudine Didanosine |
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What is each NRTI's adverse effect? (most important ones at least)
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Abacavir - hypersensitivity reaciton
Tenofovir - GI upset, farts, nephrotoxicity |
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What NRTI's were taken off the makret due to pancreatiitis and periperhal neuropathy? What is this adverse effect called?
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Stavudine and Didanosine, they cause LACTIC ACIDOSIS... including pancreatitis, periperhal neuropathy, vomiting, fatty liver. NEVER use during pregannciy b/c of all this
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What are some general adverse effects for all NRTI therapies I guess.
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Lactic acidosis
Lipoatrophy - buffalo hump and central obesity Facial Wasting |
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What are the adverse effects for NNRTI?
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SevenJohnson syndrome rash
Elevated liver enzymes Hypersenstiivy with nevirapine Neuropsychiatric with Efavirenz |
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What NNRTI causes life threatening hypersensitivity reaction in liver, leading to hepatotoxicity?
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Nevirapine
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What adverse effects does Efavirenz cause (an NNRTI)
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Neuropsychiatric (crazy dreams)
Possibly not safe during pregnancy (neural tube doesn't close) |
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What antiviral drug is completely excreted thru liver?
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PI's
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What are the two big PI's mentioned?
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Ritonavir and Saquinavir
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Adverse effects of PI's
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Gi intolerance the big one
Hyperbilirubinemia - atazanavir, indinavir, so stay hydrated Hepatotoxicity |
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What does Ritonavir do to metabolism/
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Inhibits CYP3A4
AND inhibits efflux pump |
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What "metabolic complications" (I guess like other adverse effects) do PI's cause?
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Glucose intolerance - rare diabetes
Lipodystrophy Hyperlipidemia Osteonecrosis of femoral head |
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What ARV cause femoral head necrosis?
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PI's
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What ARV cause resistance to insulin, leading to diabetes possibly?
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PI's
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What is the only fusion inhibitor?
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Enfuvirtide (Fuzeon!)
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How does Enfuvirtide work? What are the downsides?
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It's a fusion inhibitor that inhibits entry of HIV into CD4 cell by binding to gp41 on viral membrane.
Downsides - only active when injected... expensive, hypersensitiviteis |
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Adverse effects of Enfuvirtide?
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Injection site reactions
Hypersensitivity reaction Increased incidence of bacterial pneumonia |
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What are the CCR5 inhibitor drugs?
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Just Maraviroc
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How does Maraviroc work?
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It's a CCR5 inhibitor that binds to that recpeotr on CD4 cels and prevents HIV from entry. But this requires a special test to see what your virus binds to
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Maraviroc adverse effects
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Hepatotoxicity
Dizziness Hypotension Possible MI, CV events |
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What is the integrase inhibitior drug?
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Raltegravir
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How do you use Raltegravir (an integrase inhibitor)
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you give it with more than one drug, prevents resistance
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Raltegravir adverse effect (it's an integrase inhibitor)?
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mild - N&V
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What are the pros of earlier HIV treatment?
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1) harmful effects of uncontroled viremia are prevented
2) more treatment options: improved potency, tolerability, durability 3) increased ability to suppress virus w/ multidrug resistance 4) DIMINISHED EMERGENCE OF RESISTANCE |
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What are the preferred initial treamtment options?
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1) NRTI - Tenofovir or Abacavir
2) Then another set of your choice: - NNRTI (Efavirenz) - PI (Atazanavir + ritonavir) or - SSTI - Raltegravir |
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What is the "one pill" HIV drug treatmnet?
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Atripla!
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When does CD4 count drop to dangerous levels (like what does the viral count have to be)?
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It has to be at .5 log, or 3 fold increase of baseline.
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What degree of viral suppression is resistance the greatest?
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"medium"
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What is the most frequent hepatitis?
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HBV
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What are the features HAV infection?
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Fecal-oral transmission
- no carrier state - eating shellfish from contaimnated water is common way to get it |
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Symptoms of HAV
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incubation - 14-45 days
May developed distaste for cigaretes Initially - fever, headache, nausea, hepatosplenomegaly Cholestasis, dark urine, caly colored stools |
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T/F - there is an HAV vaccine.
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true
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How is HEV transmitted?
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Fecal-oral or waterborne
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What type of virus is HEV?
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non-enveloped single stranded RNA virus
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What does the HEV disease look like?
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It is a self limiting disease with no carrier state --> high mortality in pregnant women. Seen in ppl who eat raw pork (gross)
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What type of virus in HBV?
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Enveloped ds and ss DNA (both together in the same capsule). It has reverse transcriptase (b/c it's life cycle has an RNA state), DNA polymerase, and RNase H, for some reason
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How is HBV transmitee?
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Sexual
Parenteral Perinatal Needle stick |
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Which is more infectious, HBV or HIV?
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HBV, 100x more infectious
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What HBV antigen is used in vaccine?
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HBsAg (surface)
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What HBV antigen is used as an indicator of viral load?
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HBeAg
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What risk group is greatest for HBV infection?
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IDU users
Children - develop chronic hepB Adults - develop acute hepB immunosup - develop chronic hepB |
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How many acute hepB infections will proceed to resolution, and how many will go on to have "HbsAg for more than six montsh"
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90% - reslution
9% - HbsAg -of these, 50% will resolve |
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What is the "core window" for HBV mean?
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It's where you do a test and only see Anti-HBc IgM antibodies...(2-16 weeks)
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What indicates chronic HBV?
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When a paitnet has HBsAG in their serum for more than 6 months
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What do we use to treat HBV?
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Interferon alpha
Lamivudine - nuceloside analog that interferes with HBV But cure is just unrealistic |
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Why is HBV DNA resistant?
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It's protected intracellularly b/c it's a closed circle
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What type of person is the only person that HDV can infect?
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Only a person also infected with HBV
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What are the clincal featuers of HDV infection?
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Coinfection (with D and B) - acute severe disease, but not chronic
Superinfection (D later after B) - chronic HDV infection, high risk of severe liver disease |
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Where is HDV common?
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middle eastern countries, africa, and southern italy.... rare in US
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What type of virus is HCV?
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RNA virus of Flavivirus family
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T/F - do you get immunity to HCV after infection?
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No... so ... false. And there is no vaccine. Each person has a quasi-species
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What is the most common reason for liver transplants?
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HepC
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What is the pathology of HCV?
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- most infections getf acute hepatitis, 85% progress to chronic, vigurous immune respons, 20% results in cirhosis and 25% of THOSE developed hepatocellualr carcinoma
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Low liver enzymes and high anti-HCV indicate what?
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a long term chronic HCV infection.... you don't see elevated ALT unless it's like the first 2-4 months of infection. What makes it even hard to diagnose is that viral load will randomly drop
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Risk groups for HCV
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UVDU
Sexual related Health workers congenital... is rare |
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Symtpoms of HCV?
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they are asymptomatic for the most part, until complete liver failure (yikes)
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What is a nucelic acid test for HCV used (aka PCR)
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Used mainly to follow treatment -
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Why did the FDA recommend that IVDU's not recieve HCV treatment?
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b/c interferon can cause depression, and they already have sucky lives I guess
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How do you treamt HCV?
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interforn and ribavirin for 6 months to 1 year.
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Side effects for interferon treatment of HCV?
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depression,
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t/f - HCV can be cured.
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TRUE! 50-60% were cured using interferon/ribavirin treatment
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How do you know HCV treatmnet is failure?
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If, after 12 weeks, the viral load didn't drop greater than 2 log decrease (aka 99%)
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What does viral load and genotype predict with HCV disease?
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Viral load doesn't predict progression of disease
Genotype doesn't predict progression of disease BUT they both predict and indicate response to drug therapy |
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What viruses are included in Paramyxoviruses?
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Measles
Parainfluenza Mumps RSV |
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What type of viruses are paramyxoviruses?
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RNA - linear, non-segmented single strand
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What kind of vaccine is the measles vaccine?
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live attenuated. NOTE - it is ineffective in presecne of maternal antibodies
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How do you manage measles infection?
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support
Vit A for severe disease or if Vit A deficiency is likely |
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Parainfluenza viruses are what kind?
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Paramyxovirus
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What do parainfluenza viruses cause? What is it treated with?
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croup, treated with epinephrine and steroids
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What type of virus is MUMPS?
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a paramyxovirus
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Clincial manifestations of Mumps?
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similar to measles, inoculation of respiratory tract, local replication, viremia, systemic infeciotn, lead ot parotid gland and parotitis, alos pancreatitis (possible cause of diabetes), go to testes, peripheral nerves, CNS
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What is a classical manifestation for Mumps?
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Parotitis (parotid gland inflammation)
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What is hte greates cause of viral acute lower respiratory tract infection in children
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RSV
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What does the RSV illness look like?
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Severe illness occurs in infants 2-6 months of age. pneumonia and bronchiolitis, occurs in winter. rapid breathing, retraction of chest, crackles and wheezes in lungs.
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What does RSV form in histology? What about X ray?
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it forms multinucleated syncytial cells. In X ray you see hyper-expanded lung
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What do you do to treat RSV?
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prevention - no vaccine, but monloconal antibody (palivizumab) for people at risk
supportive care given |
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How many children does Measles kill a year?
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164,000
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T/F - RSV (a paramyxovirus) is the most common viral cause of lower respiratory tract infections in children and IS the most common cause of bronchitis.
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True
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What does amantadine and rimantadine do?
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interfere with M2 protein and inhibit virion uncoating to treat influenza
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What does Zanamivir and oseltamivir do?
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neuramindiase inhibiors interefere with virion release at cell surface
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the only arboviral vaccines
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yellow fever
japanese encephalitis |
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Types of Arbovirus catagories, and their properties.
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Alphavirus - enveloped, single stranded, linear, positive RNA, Causes the encepahlitis (EEE, WEE, etc)
Flavivirus - single, linear, enveloped +RNA, causes West Nile Bungavirus |
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mosquito that carries yellow fever and other common arboviruses
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Aedes mosquito
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What is the Faget sign associated with?
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yellow fever - bradycardia inappropriate for the degree of fever
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What is diagnostic of yellow fever, after taking a liver biopsy?
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Councilman bodies
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Before WNV, what was the most common endemic arbovirus in the US?
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LaCrosse encephalitis
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What is one of the only tick-born viruses in U.S.? What family is it in?
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colorado tick fever, it is a type of retrovirus (member of Reovirus family)
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What type of virus are papilomaviruses?
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non-envoleoped (naked) dsDNA, circular
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types of enteroviruses
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poliomyelitis
hepA Coxsackievirus Enterovirus Echovirus |
|
Stats on poliovirus replication (you need to know)
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90% - asymptomatic
5% - minor/abortive illness 1-2% - non-paralytic progression to CNS 0.1 - 2% - paralytic poliovirus, 4 days after minor illness |
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Describe the 2 vaccines for polio
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Salk - killed virus
Sabin - live, attenuated virus (which can revert to virulent forms) |
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What are the major categories of respiratory viruses?
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1) orthomyxovirus - influenza, enveloped; segmented, (-) RNA
2) paramyxoviruses - parainfluenza, respiratory syncytia virus; enveloepd, nonsegmented, (-) RNA 3) Picornavirus - Rhinovirus, non-enveloepd, (+) ssRNA 4) Coronavirus - envleoped, (+) ssRNA 5) Reovirus - non-enveloped, sigmented (-) dsRNA 6) ADenovirus - non-enveloped, linear dsDNA |
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What is the only double stranded RNA virus?
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Reovirus
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What type of virus is adenovirus?
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non-encapsulated, linear dsDNA virus
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How do you distinigush the different subgroups of adenovirus?
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Often by hemagglutination
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How long does adenovirus last on surfaces
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over a month, very resilient b/c it has no envelope
|
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What virus often casues keratoconjunctivit
|
Adenovirus
|
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3 antigens on adenovirus surface
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Hexon, penton base, fiber
|
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What receptor do adenovirus and coxsackie virus share?
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CAR receptor (found in heart and w/ coxsacke can cause myocarditis)
|
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Where does the adenovirus life cycle replicate?
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in the nucleus --> except for protein syntehsis which is in the cytoplasm
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Where does herpes simplex virus establish latent infection (same w/ chicken pox)
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in dorsal root ganglia
|
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What are the symptoms of EBV and HCMV?
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Mono like syndrome. Initial infection of mucosa and salivary gland, then seeding in B lymphocytes
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Which Herpes viruses cause Roseola?
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HHV6/7
|
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Classes of herpes virus:
|
1) alpha - herpes simplex, VZV. Latent in sensory ganglion
2) beta - CMV and HHV6/7, latent in salivary glands, kidneys 3) Gamma - EBV, replicate in endotheliali and lymphoblastic cells |
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How does herpesvirus enter cell?
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By fusing with cell membrane and releasing nucelocapside into cell
|
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How does herpesvirus replicate?
|
alpha genes -immediate early proteisn - regulate gene transcription and cell takeover
Beta genes - early proteins - transcription factors and enzymes (like DNA pol) Gamm genes - Late protein which are sturctural |
|
Diff HSV?
|
HSV1 - oral, ocular, encephalits
2 - genital, ocular, meningitis |
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HSV receptor on cells it uses to bidn?
|
Nectins
|
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What is Acyclovir and Valacyclovir and Penciclovir used for?
|
A nucleoside analog that treats genital herpes, targets viral DNA synthesis. big one to remmeber if Penciclovir. Drugs act only on replicating virus, not latent virus
|
|
complications of mononucleosis (EBV)?
|
Menigitis, encepahlits
Guillain-Barre syndrome Alice in Wonderladn hallucinations |
|
What can EBV cause cancer wise
|
Burkitt's lymphoma
|
|
What drugs can treat EBV?
|
none
|
|
What is diagnostic of HCMV? (cytomegalovirus)?
|
Cytomegalic cell with "owl's eye" inclusion.
|
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What does HCMV cause?
|
congetinal retardation, hearing loss
pneumoniits retinitis |
|
What drugs treat HCMV?
What drug can you not use? |
Ganciclovir
ValGanciclovir Cidofovir You can't use Acyclovir, not effective! (it is effective for herpes simplex) |
|
What do HHV6/& cause?
|
HHV6/7 - Roseola, common rash in childhood. Leads to lifelong infection. Fever, rash.
|
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What does HHV8 do?
|
Causes Kaposi's Sarcoma.
|
|
What is Kaposi's sarcoma?
|
A HHV8 infection in B lymphocytes that goes on to infect other cells (like endothelium, epithelium) infects AIDs patients (very closely associated with AIDS)
|
|
What herpes virus is transmitted via monkey bites? What do you treat with?
|
Herpesvirus simiae - 75% fatal, extremely serious. Treat with acyclovir and ganciclovir
|
|
2nd most widespread tropical disease (after malaria
|
Dengue
|
|
What is the urban vs. jungle aedes mosquito?
|
Aedes aegypti - jungle
Aedes albopictus - urban |
|
3 important points with emerging viruses?
|
1) respiratory viruses have the most explosive potential
2) 1st element is adaptation to human to human spread 3) infectiousness during pre-symptomatic phase makes containment difficult |
