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Virology + Antiviral

Day 7

Which type of viral genetics is associated with worldwide influenza pandemics? Reassortment (viruses with segmented genomes exchange segments)
In which type of viral genetics will the progeny revert back to the old virus because there is no genetic exchange (virus A only picks up nucleocapsid proteins from virus B) Phenotypic mixing
Which vaccines are egg based and require a skin test for people with egg allergies prior to administration? The flu and yellow fever (yellow like an egg yolk)
What is the ONLY live vaccine that may be given to HIV patients? MMR (can only give to HIV; do NOT give to AIDS patients); besides MMR, live vaccines should NEVER be given to immunocompromised patients or their close contacts (herd immunity)
Which form of the influenza vaccine is live? Intranasal form only (IM form is killed vaccine)
Which vaccines are live? Smallpox, yellow fever, chickenpox (VZV), Sabin's polio, MMR Chickens are alive. Sabin (saber) tooth tigers are alive.
Which vaccines are killed? Rabies, Influenza, salk Polio (k=killed), and hAv (RIP Always)
Which vaccines are recombinant? HBV and HPV
What is the only single stranded DNA virus? Parvoviridae (parvovirus B19)
What is the only double stranded RNA virus? Reoviridae (Reovirus= Colorado tick fever, Rotavirus= diarrhea in children)
Where do DNA viruses replicate? In the nucleus
Where do RNA viruses replicate? What are the exceptions to this rule? In the cytoplasm; except for influenza and retroviruses
Most enveloped viruses acquire their envelopes from the plasma membrane when they exit the cell. Which virus is an exception to this rule? How does it acquire its envelope? Herpesviruses; acquire envelopes from nuclear membrane
What are the DNA viruses? Herpesviruses, HepaDNAvirus, Adenovirus (sounds like "A DNAvirus"), Parvovirus, Papillomavirus, Polyoma virus, and Pox virus (HHAPPPPY)
Sporadic temporal lobe encephalitis HSV-1
Virus assoc'd with t(8;14) EBV (Burkitt's lymphoma= t(8;14)
Infection in immunocompromised patients, especially transplant patients CMV
AIDS retinitis CMV
Roseola HHV6
Kaposi's sarcoma HHV8
Positive monospot infectious mononucleosis EBV
Negative monospot infectious mononucleosis CMV (listeria and toxoplasma can also cause - monospot test)
Neonatal herpes HSV2
Cowdry Type A owl's eye inclusions CMV
High fevers that break and are then followed by a rash; may cause seizures if child is susceptible to febrile seizures Roseola (HHV6)
Remains latent in trigeminal ganglia HSV1 (makes sense cuz it's on your face!)
Remains latent in sacral ganglia HSV2 (makes sense cuz it's on your butt!)
Remains latent in trigeminal and dorsal root ganglia VZV
Herpes virus that infects B cells EBV (B for B cells! Woo hoo!)
Herpes virus that infects mononuclear cells CMV
What does the Tzanck test look for? Multinucleated giant cells in HSV identification
Fever, hepatosplenomegaly, exudative pharyngitis, and lymphadenopathy (esp posterior cervical nodes) EBV
What does a positive monospot mean? Heterophil antibodies are present
Assoc'd with nasopharyngeal CA EBV
Not a retrovirus but has reverse transcriptase Hep B
Febrile pharyngitis (w/acute hemorrhagic cystitis), pneumonia, and conjunctivitis; may be seen with GI problems Adenovirus (DNA)
Aplastic crises in sickle cell disease Parvovirus B19
RBC destruction in fetus leading to hydrops fetalis Parvovirus B19
Anal cancer Papillomavirus (16, 18)
Progressive multifocal leukoencephalopathy in HIV patients JC virus (Polyomavirus; DNA)
Vaccinia Cowpox (poxvirus; DNA) which causes milkmaid's blisters
What is the treatment for molluscum contagiousum (Poxvirus; DNA)? Leave them alone! What did they ever do to you?
#1 cause of fatal diarrhea in children, especially in the winter months Rotavirus (Reovirus; RNA)
PicoRNAviruses that cause meningitis and myocarditis Echovirus and coxsackievirus
PicoRNAvirus that affects the motor neurons of anterior horn and causes paralysis Poliovirus
PicoRNAvirus that causes acute viral hepatitis HepA
Hepvirus (RNA) that causes a form of hepatitis that is enterically-transmitted and is associated with epidemics and a high mortality rate in pregnant women HepE
What are the flaviruses (RNA)? HCV, Yellow fever, Dengue, St Louis encephalitis, and West Nile virus (flavi means yellow, so think yellowing and jaundice)
What are the retroviruses (have reverse transcriptase to synthesize DNA from RNA)? HIV-AIDS and HTLV (Human T-lymphotropic Virus)- T cell leukemia
German measles Rubella (Togavirus; RNA)
Eastern and Western equine encephalitis Togavirus (RNA)
Common cold Coronavirus (RNA) and Rhinovirus (Picornavirus; RNA)
Colorado tick fever Reovirus (RNA)
Aseptic meningitis in a kid from a swimming pool Echovirus (picornavirus; RNA)
Aseptic meningitis, herpangina, febrile pharyngitis, hand, foot, and mouth disease, myocarditis Coxcackievirus (picornavirus; RNA)
Viral gastroenteritis Norwalk virus (calcivirus; RNA)
Why are patients susceptible to a secondary infection with strep pneumo, staph aureus, or H flu after infection with influenza? B/c of virally induced damage to mucociliary clearance mechanisms in respiratory epithelium
What virus causes bronchiolitis in babies? What is the treatment of choice? RSV (paramyxovirus; RNA). Tx is ribavirin
Rubeola Measles (paramyxovirus; RNA)
Brassy, low-pitched cough with an infected larynx Croup (PARAinfluenza; PARAmyxovirus; RNA); cough is also described as a barking seal cough
Virus that produces Ebola/Marburg hemorrhagic fever Filovirus (RNA)
Virus assoc'd with animal urine; may cause hemorrhagic fever and penumonia Hanta virus
Which liver tropic virus is a part of the deltavirus family? HepD
How are all picornaviruses spread? What is the one exception? All are enteroviruses, so they are spread via the fecal-oral route. Rhinovirus is the one exception. Picornaviruses include poliovirus, echovirus, rhinovirus, coxsackievirus, and HAV
Why is rhinovirus, unlike the other picornaviruses, unable to infect the GI tract? It is acid lable, so it gets destroyed by stomach acid.
Transmitted by Aedes mosquitos; high fever, black vomitus, and jaundice Yellow fever virus(Flavivirus; RNA)
High fever, jaundice, white coat on center of tongue with red at the tips and sides of the tongue Yellow fever virus (Flavivirus; RNA)
Child with severe greenish diarrhea in the winter months Rotavirus (Reovirus; RNA); very contagious!
How does rotavirus cause diarrhea? VIllous destruction with atrophy leads to decreased absorption of Na and water
What influenza antigen is responsible for promoting viral entry? HemaggLUTININ (LUTS INfluenza IN!)
What influenza antigen is responsible for promoting progeny virion release? NEURaminadase (like a NEURsery/nursery letting the little progeny/kiddies out at the end of the day!)
What change in the influenza virus is responsible for the need to get a new flu shot each year? Genetic drift (minor; epidemic; changes based on random mutation). Compare to genetic shift which is reassortment of viral genome, major, and pandemic.
Fever, postauricular tenderness, lymphadenopathy, fine truncal rash German measles (caused by Rubella which is a togavirus)
Virus that causes mild infection in children, but has serious congenital sequelae like PDA and pulmonary stenosis in neonates Rubella (a togavirus that causes German measles in children)
Which group of viruses contain a surface F (fusion) protein which causes respiratory epithelial cells to fuse and form multinucleated cells? Paramyxoviruses (parainfluenza/croup, mumps, measles, RSV)
What drug is used in RSV to neutralize the surface F (fusion) protein? Palivizumab
Koplik spots, cough, coryza, conjunctivitis Rubeola (measles) virus (a paramyxovirus); also includes a head-to-toe rash which includes hands and feet
Parotitis, Orchitis, and aseptic meningitis; may lead to sterility in post-pubescent boys Mumps virus (paramyxovirus; RNA)
Negri bodies in cytoplasmic inclusions in neurons (commonly in Purkinje cells of cerebellum) Rabies virus (Rhabdovirus; RNA)
Bullet-shaped capsid Rabies (think about Old Yeller getting a bullet b/c he had rabies)
Fever, malaise--> Agitation, photophobia, hydrophobia--> paralysis, coma--> death Rabies virus (Rhabdovirus; RNA)
What should occur immediately upon exposure to a rabies vaccine, even though the incubation period of the virus lasts for weeks to months before symptom onset? Prophylactic vaccination
What is the path of infection of the rabies virus? Wound--> neuron axons--> salivary glands
How does the rabies virus travel to the CNS? Travels to the CNS by migrating in a retrograde fashion up the n axons
A patient presents with restlessness, agitation, and dysphagia which progresses to a coma 30-50 days following an exposure to cave bats. Rabies virus (Rhabdovirus; RNA)
Rash that starts at head and moves down to feet, disappearing in the same sequence as it developed Measles (think of a can of red paint being poured over the patient's head; as it drips down the body to the feet, it comes off of the head, shoulders, etc.); Paramyxovirus: Rubeola
Fine truncal rash only lasting for 3 days Rubella (Togavirus)= German (3 day) measles
Rash that develops only after a fever breaks Roseola (HHV6)
Which virus can have a rare complication of sclerosing encephalitis years after apparent recovery from the initial infection? Measles (paramyxovirus; RNA); oligoclonal bands of antibodies to the virus are found in the CNS while antibodies to the M component of the virus are not
Name that hepatitis!: short incubation, no carriers HepA (picornavirus); fecal oral route of transmission
What type of food is the typical culprit of HAV infection? Raw or steamed shellfish
Do children with HAV infection typically present with jaundice? No; they are usually anicteric (no jaundice)
Name 5 ways that HAV can be inactivated. 1. Water chlorination 2. Bleach 3. Formalin 4. UV irradiation 5. Boiling to 85C for 1min
Close contacts of an HAV infected person should be prophylaxed with _______. Immunoglobulin
Name 3 histological findings seen in all cases of acute viral hepatitis. 1. Diffuse ballooning degeneration (heaptocyte swelling) 2. Mononuclear cell infiltrates 3. Councilman bodies (eosinophilic apoptotic hepatocytes)
What is the MC cancer caused by HepB and HepC? What is the assoc'd tumor marker that should be regularly checked in infected patients? Hepatocellular carcinoma; AFP
Name that hepatitis!: Primarily a sexual transmission Hep B (You get it in Bed! Lucky you!)
Name that hepatitis!: Primarily transmitted in blood Hep C (the Clean one)
Name that hepatitis!: The only one that is a DNA virus Hep B
Name that hepatitis!: Virion enzyme is a DNA-dependent DNA polymerase Hep B
What is the path of synthesis of progeny ds DNA in Hepatitis B virus? ds DNA--> template + RNA--> progeny ds DNA
Name that hepatitis!: Common cause of hepatitis among IV drug users in US. Hep C
Name that hepatitis!: Requires HBsAg as its envelope Hep D
Name that hepatitis!: Enteric transmission, causes waterborne epidemics, high fatality rate in pregnant women Hep E
Name that hepatitis!: Predispose patients to chornic active hepatitis, cirrhosis, and hepatocelluar carcinoma Hep B and C
Why are hepatitis A and E able to infect via the fecal-oral route? B/c naked viruses do not rely on an envelope, they are not destroyed in the gut.
Congenital cataracts (white pupils- bilateral unlike retinoblastoma), sensory neural deafness, and PDA Congenital rubella (German measles), a togavirus (RNA)
How can congenital rubella be prevented? Giving MMR (a live, attenuated vaccine) to women >4 mos b/f getting pregnant
Interpret that hepatitis serologic marker!: Anti-HAV Ab (IgM) Active infection with HepA
Interpret that hepatitis serologic marker!: Anti-HAV Ab (IgG) Prior HAV infection (IgG= Gone!) ; protected against future infection
Interpret that hepatitis serologic marker!: HBsAg Infected with HepB
Interpret that hepatitis serologic marker!: anti-HBsAg Immunity to HepB (either recovered from an infection or received passive immunization like a vaccine)
Interpret that hepatitis serologic marker!: anti-HBcAg IgM acute or recent HepB infection
Interpret that hepatitis serologic marker!: anti-HBcAg IgG chronic HepB
Interpret that hepatitis serologic marker!: HBeAg Active HepB infection; making lots of viruses so you have high transmissibility
Interpret that hepatitis serologic marker!: anti-HBeAg Low transmissibility
Which hepatitis serologic marker is positive during the window period? Anti-HBcAg (IgM)
Which hepatitis serologic marker first apepars before the onset of symptoms, peaks when the patient is most ill, and then becomes undetectable in 3-6 mos? HBsAg
What is the only hepatitis serologic marker that will be positive in patients who were only vaccinated against HepB? Anti-HBsAb
Why don't neonates with HepB infection present with severe hepatic injury? Their immune system is still too immature to mount a major response against the virus, so the damage is minimal (until they develop a stronger immune response).
Breakbone fever: musle/joint pain, headache, retro-orbital pain Dengue fever
Tourniquet test (WHO field test for diagnosing hemorrhagic fever) can diagnose this illness Dengue fever
Meningitis, encephalitis, m weakness, flaccid paralysis (via anterior horn involvement), alterations in consciousness, and possibly death; birds are the reservoir and mosquitoes are the vectors West Nile virus; tx is supportive
URI, GI symtpoms (diarrhea), fever, pancytopenia, elevated aminotransferases (AST, ALT) Avian influenza; H5N1 (spread from bird--> human)
What is the treatment for avian influenza/H5N1? Oseltamavir
Typical flu symptoms with GI symptoms H1N1 influenza/swine flu
What is the treatment for H1N1 influenza/swine flu Oseltamivir or zanamivir to high risk or severely ill patients
What is the strain makeup of H1N1? 2 swine flu strains, 1 human strain, and 1 avian strain. Yummy!
Steeple sign on x-ray parainfluenza/croup (RNA virus)
Can ribavirin be used to treat RSV bronchiolitis? Only in adults; in children ribavirin should NOT be given; give kids albuterol or racemic epinephrine and oxygen
Name that antiviral!: Blocks viral penetration/uncoating (M2 protein) Amantadine (a man to dine takes off his coat) and rimantadine
WHy can amantadine be used to treat Parkinson's disease? Because it causes the release of dopamine from intact nerve terminals
Why is amantadine rarely used to treat the flu? 90& of all influenza A strands are resistant; may be given as a prophylaxis though
Name that antiviral!: Inhibits influenza neuraminidase (decreases release of progeny virus) Zanamivir and oseltamivir
What are zanamivir and oseltamivir used to treat? Influenza A and B
Name that antiviral!: Inhibits syntehsis of guanine nucleotides by compeitively inhibiting IMP dehydrogenase Ribavirin
What is ribavirin used to treat? RSV (in adults only), chronic Hep C
What are the side effects of ribavirin? Hemolytic anemia and severe teratogen (unrelated, but think of how ribavirin can't be used in kids. ribavirin is rotten for kids and bad for babies)
What are the treatments used for Hep C (2)? Ribavirin and IFN alpha
Name that antiviral!: Monophosphorylated by HSV/VZV thymidine kinase. Preferentially inhibits viral DNA polymerase by chain termination Acyclovir
What are the clinical uses for acyclovir? treat HSV1/2, VZV, and EBV
Why are higher doses of acyclovir required to treat EBV? Because EBV produces a different thymidine kinase than HSV and VZV do whic prevents it from easily converting acyclovir into its active metabolites.
Which agent should be used to treat herpes zoster? Famciclovir
What toxicity can result if acyclovir is given IV? Nephrotoxicity; hydration can help prevent this
What is the mechanism of resistance to acyclovir? Lack of viral thymidine kinase (can't activate acyclovir)
Name that antiviral!: 5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase; preferentially inhibits viral DNA polymerase Ganciclovir
What is the clinical use for ganciclovir? CMV, espeically in immunocompromised patients
What is the mechanism of resistance to ganciclovir? Mutated CMV DNA polymerase or lack of viral kinase
Name that antiviral!: Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Foscarnet (pyroFOSphate analog)
What differentiates foscarnet from acyclovir and ganciclovir? Foscarnet does NOT require activation by viral kinase
What is the clinical application for foscarnet? CMV retinitis in immunocompromised patients when ganciclovir fails and acyclovir-resistant HSV
What toxicity is seen with foscarnet? Nephrotoxicity
What is the mechanism of resistance to foscarnet? Mutated DNA polymerase
Which antiviral has the following toxicities: leukopenia, neutropenia, thrombocytopenia, and renal toxicity Ganciclovir (more toxic to host enzymes than acyclovir)
How do interferons work as anti-viral therapy? They are glycoproteins synthesized by virus-infected cells that block replication of both RNA and DNA viruses
Which interferon is used to treat chronic HepB and C, and Kaposi's sarcoma IFN-alpha
Which interferon is used to treat MS? IFN-beta
Which interferon is used to treat NADPH oxidase deficiency? IFN-gamma
HIV envelope protein that mediates attachment to the host T cell gp120 (the grabber)
HIV envelope protein that mediates fusion and penetration/entry into the host T cell gp41
How does HIV reverse transcriptase work? Synthesizes dsDNA from RNA (HIV is diploid and has 2 molecules of RNA inside)
What enzyme allows HIV-synthesized dsDNA to be incorporated into the host genome? Integrase
Which structural gene encodes for HIV reverse transcriptase? pol
Which structural gene encodes for HIV gp120 and gp41 envelope proteins? env (for envelope)
Which structural gene encodes for HIV p24/capsid protein? gag (you gag when you try to swallow a capsule/capsid)
X4 HIV virus only uses which T cell receptor? CXCR4
R5 HIV virus only uses which macrophage receptor? CCR5
How does a homozygous CCR5 mutation affect HIV infection? Makes host immune to infection
How does a heterozygous CCR5 mutation affect HIV infection? Causes a slower course of infection
How is an HIV diagnosis made (what tests are used)? ELISA (high sensitivity, so rules OUT with a - result). If ELISA is +, confirm with a Western blot assay (high specificity, so rules in with a + result).
How are HIV PCR/viral load tests used clinically? To monitor effect of drug therapy on viral load or to see if the baby of an HIV + mother is truly infected (baby will have anti-gp120 Ab b/c they cross the placenta, but doesn't necessarily mean that they have the virus)
When are false negative tests to HIV most common? In first 2 months b/c there is not enough Ab for test to be + yet.
What "count" is used to make an AIDS diagnosis? CD4 <200. Also, HIV+ with an AIDS indicator condition (e.g., PCP pneumonia), or CD4/CD8 ratio <1.5
What prophylaxis can be given to HIV + pregnant women to reduce transmissiblity to the baby? Zidovudine (nucleosie analog) which is a reverse transcriptase inhibitor
What are the opportunistic infections of the brain seen in AIDS? Cryptococcal meningitis, toxoplasmosis, CMV encephalopathy, AIDS dementia, and PML (JC virus)
CMV causes what opportunistic GI infection in AIDS patients? CMV colitis
Which genital cancer is considered an opportunistic infection in AIDS patients? Cervical cancer (HPV)
When CD4 counts drop below 50, what prophylaxis should only be administered in the case of a past history of cryptococcal meningitis? Fluconazole
HIV patient with dementia HIV encephalitis
Infectious protein with beta pleated sheets that can result in spongiform encephalopathy (e.g., Creutzfeldt-Jakob disease) Prions
What is the mechanism of action of the -navir drugs? Protease inhibitors: prevent maturation of new viruses which is normally mediated by HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional parts. NAVIR TEASE a proTEASE.
What is the mechanism of action of nucleoside reverse transcriptase inhibitors? Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain.
What is required for activation of NRTIs? Thymidine kinase phosphorylation
Which NRTI is used for prophylaxis during pregnancy? Zidovudine
What are the NRTIs? Zidovudine, Stavudine, Didanosine, Zalcitabine, and Abacavir (Have you dined (vudine) with my nuclear (nucleosides) family?)
Which NRTIs can cause pancreatitis and peripheral neuropathy? Didanosine, Zalcitabine, and Stavudine
Which NRTI causes megaloblastic anemia and bone marrow suppression? How can the bone marrow suppression be reversed? Zidovudine; treat bone marrow suppression with G-CSF and erythropoietin
Which HIV anti-viral class causes lactic acidosis? NRTIs
Which HIV anti-viral class causes a rash? NNRTIs
Which HIV anti-viral class causes hyperglycemia (due to increased insulin resistance; may cause diabetes), GI intolerance, and lipodystrophy? Protease inhibitors (navirs)
Which protease inhibitor causes thrombocytopenia? Idinavir
How are non-nucleoside reverse transcriptase inhibitors (NNRTIs) different from nucleoside reverse transcriptase inhibitors (NRTIs)? NNRTIs bind to reverse transcriptase at a site different from NRTIs and do NOT require phosphorylation to be active or compete with nucleotides. NNRTI binding is non-competitive.
What are the NNRTI drugs? Nevirapine, Efavirenz, and Declaviridine (NEVIR EFIR DELAVIR <never ever deliver> nucleosides; all have "vir" in the middle)
What is the mechanism of action of enfuvirtide? Binds viral gp41 subunit to inhibit conformation change required for fusion with D4 cells, blocking entry and replication (enFUvirtide is a FUsion inhibitor)
Which HIV antiviral carries an increased risk of bacterial pneumonia? Enfuvirtide (may also cause hypersensitivity reaction at site of subq injection)
Which anti-mycobacterial drug should never be used with protease inhibitors? What drug should be used instead? Rifampin (revs up p450 so decreases serum levels of protease inhibitors); use rifabutin instead
What is the MC outcome of HepB infection in an adult? Complete resolution (not progression to cirrhosis or cancer)
From which cells does Kaposi's sarcoma tumor arise? Mesenchymal cells
What causes hepatocyte damage in HepB? The presence of viral HBsAg and HBcAg on the cell surface stimulates the host's cytotoxic CD8+ T lymphocytes to destroy the infected hepatocytes. Remember that the HepB virus itself does not have a cytotoxic effect, and that the Ab are neutralizing.
Name 3 causes of esophagitis (dysphagia and/or odynophagia) in HIV. 1. Candida albicans 2. HSV-1 3. CMV
Dysphagia and odynophagia in an HIV patient with yeast cells and pseudohyphae that invade mucosal cells on histologic exam. Candida albicans--> esophagitis
Dysphagia and odynophagia in an HIV patient with punched out ulcers containing eosinophilic intranuclear inclusions in multinucleate squamous cells at the ulcer margins. HSV-1--> esophagitis
Dysphagia and odynophagia in an HIV patient with linear ulceration and both intranuclear and cytoplasmic inclusions CMV--> esophagitis
Created by: sarah3148



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