9.30 DNA viruses – Flashcards
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What's the range of DNA genome sizes? |
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some of the smallest (5kb) to largest (over 200 kb) of all viruses |
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Describe the herpesvirus genome. |
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DS, linear |
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Describe the hepadnavirus genome. |
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DS, circular |
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Describe the adenovirus genome. |
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DS, linear |
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Describe the papovavirus genome. |
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DS circular |
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Describe the poxvirus genome. |
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DS, linear |
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Describe the parvovirus genome. |
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SS, linear |
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What are the two types of papavavirus? |
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papillomavirus and polyomavirus |
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T/F Many DNA viruses have evolved for milennia with their hosts. |
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true |
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As a consequence of co-evolution most DNA viruses can... |
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persistently infect its host (integrative and transforming potential) |
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What's the morphology/structure of parvoviruses? |
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naked icosahedral |
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What's the morphology/structure of adenovirus? |
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naked icosahedral |
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What's the morphology/structure of papovavirus (papilloma and polyoma)? |
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naked icosahedral |
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What's the morphology/structure of hepadnavirus? |
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enveloped icosahedral, pleomorphic/filamentous |
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What's the morphology/structure of herpesvirus? |
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enveloped icosahedral |
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What's the morphology/structure of pox virus? |
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multi-enveloped, ovoid brick |
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What DNA viruses are very capable of environmental persistence and are resistant to chemical inactivation? |
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non-enveloped ones |
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Name three examples of broad spectrum drugs that can target multiple viruses by targeting general entry pathways? |
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amantidine, rimantadine and tromantadine |
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Where do DNA viruses replicate? |
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in the cell's nucleus causing intranuclear inclusions (except for the poxvirus, which causes cytoplasmic inclusions) |
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What types of proteins are made by the immediate early genes? |
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regulatory/evasion (IFNs) |
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What types of proteins are made by the early genes? |
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regulatory/replication |
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What types of proteins are made by the late genes? |
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structural |
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What drugs inhibit DNA polymerase? |
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foscarnet, cidofivir |
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What drug inhibits thymidine kinase? |
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acyclovir (nucleoside analogs) |
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How do naked viruses exit the cell? |
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lysis |
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What types of viruses produce polykaryon or syncytia? |
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enveloped viruses |
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Syncytia are caused by ______ on membranes of cell or virus. |
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glycoproteins |
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In 2003, a highly deadly respiratory disease caused by a virus with the absence of nuclear inclusions and multinucleated syncytia formation was diagnosed as what type of virus? |
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coronavirus (causing SARS) |
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Why is it called an "adeno"virus? |
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first isolated from adenoids |
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What's the genome size of an adenovirus? |
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moderately sized (36-40 kb) |
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Adenovirus tropism: |
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epithelial, lymphoid, mesenchymal |
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What is adenovirus transmission? |
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respiratory and oral-fecal |
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What is the incubation time of an adenovirus? |
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5-9 days |
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What is the pathogenesis of an adenovirus? |
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direct cell damage caused by replication although the cellularimmune response against infected cells has also been implicated in damage of infected tissue |
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How do you diagnose an adenovirus infection? |
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cell-culture, viral antigen detection (IFA; immunoassay) |
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Is there an adenovirus vaccine? |
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yes, live vaccine that was used in the military but was discontinued in 1999 |
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What's the therapy for adenovirus? |
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no antiviral drugs; cidofivir or I.V. ribavirin if rampant |
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Are adenoviruses stable outside of the body? |
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yes, they are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of the body and water |
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What viruses used receptor CAR1? |
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adenovirus and coxsackievirus |
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What types of diseases are caused by adenoviruses? |
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most commonly: respiratory common: ocular infections other: gastroenteritis and meningoencephalitis |
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WWhat respiratory diseases are caused by adenoviruses? |
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adenoviral pneumonia, acute respiratory disease (ARD), endemic respiratory diases |
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How are respiratory disease adenoviruses spread? |
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coughed-out droplets |
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What ocular diseases are caused by adenoviruses? |
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epidemic conjunctivitis, sporadic-acute follicular conjunctivitis |
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How are ocular disease caused by adenoviruses commonly spread? |
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in water of swimming pools that don't have enough chlorine in them |
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T/F some people with adenovirus gastroenteritis may shed the virus in their stools for months after getting over the symptoms. |
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true |
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Adenovirus URIs manifest as... |
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tonsilitis (that may look exactly like strep- need culture to distinguish), ear infection, or croup |
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T/F Adenovirus can cause a UTI. |
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yes, rarely it causes hemorrhagic cystitis |
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Which population is susceptible to bronchiolitis or pneumonia caused by an adenovirus? |
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children (esp. small ones) |
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What virus can look exactly like whooping cough in babies? |
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adneovirus |
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Who is at risk for acute respiratory illness caused by an adenovirus? |
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military recruits, boarding schools, etc. (1-5, 7, 10, 11, 13, 14, 21) |
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What population is at risk for a pharyngitis caused by an adenovirus? |
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infants (1-5, 7) |
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What population is at risk for a gastroenteritis caused by an adenovirus? |
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infants (40,41) |
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What population is at risk for a conjunctivitis caused by an adenovirus? |
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all (3,4) |
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What population is at risk for a pneumonia caused by an adenovirus? |
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infants, military recruits (4,7) |
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What population is at risk for an acute hemorrhagic cystitis caused by an adenovirus? |
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infants (11) |
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What population is at risk for a hepatitis caused by an adenovirus? |
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infants, liver transplant patients (4,5,7,10) |
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What serotypes of adenovirus are commonly seen with respiratory disease? |
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mainly species HAdV-B and C |
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What serotype of adenovirus are commonly seen with conjunctivits? |
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HAdV-B and D |
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What type of adenovirus are commonly seen with gastroenteritis? |
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HAdV-F serotypes 40 and 41 |
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What are the symptoms of endemic respiratory disease (adenovirus)? |
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pharyngitis, tonsillitis, and nasopharyngitis (symptoms: cough, sore throat, tonsillar exudates, myalgia and headache) |
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What are the symptoms of ARD? |
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flulike, seen in military recruits. Fever, pharyngitis, cervical adenopathy, cough, myalgia, and diarrhea |
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What are the symptoms of adenoviral pneumonia? |
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fever, cough, dyspnea and wheezing. common in infants and the immunocompromised |
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What are the symptoms of sporadic acute follicular conjunctivitis caused by adenovirus? |
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benign conjunctivitis; is the most common eye infection |
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Which age group is most affected by epidemic keratoconjunctivitis caused by adenovirus? |
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common affliction across all ages |
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What re the signs of meningoencephalitis caused by adenovirus? |
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aseptic meningitis, meningoencephalitis, and encephalitis. Common amongst children and immunocompromised patients |
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Which adenovirus types caused gastroenteritis? |
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40 and 41 |
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What is the second most common cause of infantile viral diarrhea? |
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adenovirus (after rotavirus) |
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What are the symptoms and typical patient of acute hemorrhagic cystitis caused by adenovirus? |
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almost exclusively in male children: urinary frequency, bladder pain and gross hematuria |
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What is Ad14? |
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rare, emerging virus that can cause severe respiratory infection, which can sometimes be fatal, even in healthy young adults. Ad14 isolates from four states where outbreaks occurred were identical, based on DNA sequencing |
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How was the adenovirus vaccine administered? |
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live, nonattenuated via an enteric-coated tablet that would replicate once when they reach the intestine causeing an asymptomatic infection of the GI tract |
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What virus is linked to obesity? |
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adenovirus |
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Why do adenvirusese in particular have immense potential as vectors for vaccination, gene, and cancer therapy? |
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adenoviruses can be genetically altered in vitro |
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What are possible complications of using adenoviruses for gene therapy? |
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you have to limit hepatotoxicity and prevent multiple organ failure |
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How are adenoviruses used to treat cancer? |
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specific modifications on fiber proteins are used to target adenovirus to certain cell types such as tumors and then utilize the lytic properties of adenoviruses to kill tumors |
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Which viruses have been used in clinical trials for gene therapy/replacement studies? |
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adeno, retro and parvo |
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Phase ____ clinical trials are ongoing for adeno and vaccinia virus based vectors for use in immunization against a plethora of diseases. |
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II and III |
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Which viruses are used as oncolytic viral therapies? |
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herpes and adeno |
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Name the erythrovirus parvoviruses. |
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human parvovirus B 19, human bocavirus, human parvovirus 4 |
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What is the tropism of parvovirus? |
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epithelial cells in S (synthesis) phase or needs helper virus. Erythroid progenitor cells-replicates in and destroys |
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What is the transmission of parvoviruses? |
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respiratory |
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What is the pathogenesis of parvoviruses? |
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direct cell damage caused by viremia, and the humoral immune response against infected cells has also been implicated in damage of infected tissue |
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What are associated diseases of parvovirus infection? |
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fifth disease (enrythema infetiosum-common), hydrops fetalis (very rare, due to fetal anemia and not associated with fetal abnormalitis); persistent infection in immunocompromised: relapsing anemia |
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How do you diagnose parvoviruses? |
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serology, PCR or DNA probe (differntial: rubella virus) |
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What is the vaccine/therapy for parvoviruses? |
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none/human normal immunoglobulin (HNIG); red blood cell transfusion to control acute anemia |
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How big is the parvovirus genome? What are the different genes on it? |
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5 kb flanked with inverted terminal repeats (ITR), Rep gene required for DNA replication and Cap gene encodes capsid proteins |
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Why must thc cell be in S phase for viral replicationo of parvovirus? |
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because of limited number of genes and small size of parvovirus |
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Parvovirus integrates its DNA where in the host genome? |
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chromosome 19 |
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Besides when the host cell is in S phase, parvovirus can also replicate when... |
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the cell is coinfected with a helper virus |
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T/F Parvovirus is highly transmissible. |
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true, approx 60% of adults are seropositive |
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What causes erythema infectiosum? |
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aka fifth disease. Caused by parvivirus following respiratory transmission and viremia. |
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What are the symptoms of fifth disease? |
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malaise, fever, headache, chills, myalgia, maculopapular rash |
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What is the three stage rash of fifth disease? |
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1)both cheecks "slapped face" 2) maculopapular on trunk and limbs 1-4 days post cheecks 3) periodic evanescence and recrudescence lasts 1-3 weeks |
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What are examples of patients with RBC d/o's that often have complications with parvovirus infections? |
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d/o's with shoreter lifespan of RBCs: sickle cell, thalesemia, spherocytosis, disorders of hemoglobin expression |
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What are the complications of immunocompromised individuals with parvovirus infections? |
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persistence in bone marrow, persistent anemia because of failure to clear virus, MIs, neurologic disorders |
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What are complications of parvovirus infection of fetuses? |
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persistent anemia, hypoxic damage to heart and liver; edema; hydrops fetalis. Still birth if infection in first 20 weeks due to severe anemia |
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How big is the poxvirus genome? |
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>200 kb |
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What is the tropism of poxvirus? |
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respiratory epithelium to lymph nodes to skin |
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What is the transmission of DNA viruses and disease? |
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respiratory/aerogenic transmission; skin contact with lesions |
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What is the pathogenesis of pox viruses? |
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eruptions at skin (different than herpes varicella, all erupt at the same stage) due to route to reach skin; affects respiatory and intestinal tract mucosae |
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What are the associated diseases of poxvirus? |
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small pox, molluscum contagiosum; monkey pox; accidental exposure generalized vaccinia |
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How do you diagnose a pox virus? |
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histology, morphology |
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What was the first virus to be visualized under a light microscope? |
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pox virus |
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How big is the pox virus? is it ds or ss? |
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ds; 135 to 289 kpg in length |
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How many ORFs are encoded by poxvirus? |
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136-260 |
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How many genes are conserved among poxviruses? |
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49 among all; 41 among orthopoxviruses |
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Describe the genomic organizationo f poxvirus? |
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centrally located genes are most commonly conserved and encode genes essential for poxvirus replication and virion assembly. Terminally located genes are more variable and encode genes iwht regulating biological activity (e.g. host range restriction or immune evasion) |
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What are the two infectious forms of poxvirus? |
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internal mature virus (exit via lysis) and external enveloped virus (acquire envelopes in the post-golgi machinery and exit via the cell membrane |
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What two histological findings are indicative of poxvirus? |
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guarnieri bodies (b-type/basophilic inclusions), molluscum bodies (A type/acidophilic inclusions) |
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What are guarnieri bodies? |
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B-type/basophilic inclusions formed by viral DNA and DNA replication machinery. In the cytoplasm. Associated with poxvirus |
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What are molluscum bodies? |
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A type/acidophilic inclusions seen in the epidermis. A-type inclusions are accumulation of progeny virions and proteinaceous material |
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What are the two antigenically indistinguishable strains of poxviruses? |
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variola major (CFR 5-40%0 and variola minor (CFR < 1%) |
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What characteristics of smallpox allowed us to successfully eradicate it with a vaccine? |
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no subclinical infections. life-long immunity and virus clearance with resolution of disease (no carrier state). very narrow host range; no animal reservoir; availability of an effective vaccine |
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What's the incubation of smallpox? |
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12 weeks |
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What's the progressiono f the small pox rash? |
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mild rash, maculopapules, vesicles, pustules, scabs, scar |
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How do you tell smallpox from varicella? |
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chickenpox is more concentrated on trunk and face and erupt at different times. Small pox is more concentrated on extremeties and face and all erupt at the same time. |
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When was the first successful vaccination? |
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14 May 1796 cowpox virus by Edward Jenner |
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What was the vaccine used to eradicate smallpox? |
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vaccinia virus; determined that vaccine strain was not or no longer CPV but a distinct poxvirus. (volved from variola by continual passage in skin of cows or humans, derived from CPV by continued repeated pasage in skin of animals, hybridization of CPV and variola virus; natural host is extinct) |
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What is used as a gene delivery vector for smallpox innoculation? why? |
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fowlpox virus, an avipoxvirus, and modified vaccinia ankara strain. (b/c large capacity for insertion of exogenous DNA and no pre-existing immunity in mammalian hosts) |
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What are the side effects of the small pox vaccine? |
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inadvertent innoculationof self (1:1700), gneralized vaccinia (1:5000), eczema vaccinatum, progressive vaccinia/vaccinia necrosum (only in immunosuppressed, can be fatal), encephalitis (1:200,000, fatal in 20%, neurologic problems in 25%), cardiovascular (increase in MIs) |
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What is the treatment for vaccinia virus side effects? |
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vaccinia immune globulin from the CDC |
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T/F many new vaccines are being created from a modified vaccinia. |
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true |
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What is musculloscum contangiosum virus? |
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poxvirus that is a natural pathogen of humans |
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Which population is susceptible to MCV? |
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children and HIV infected individuals |
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How many strains of MCV are there? |
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4; MCV-1 is most prevalent; MCV-2 is seen mostly in adults and often transmitted by sexual contact |
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How is MCV transmitted? |
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skin-to-skin contact or by contact with fomites, except on the palms of the hands and soles of the feet |
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Which virus has the narrowest range of all poxviruses? |
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MCV only infects and replicates in the human epidermis |
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What is the incubation of molluscum contagiosum? |
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2 weeks to 6 months (mean of 6 weeks) |
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How long is the disease course of MC? |
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6-8 weeks but may last up to 2-3 months |
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What reht the MCV lesions like? |
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flesh colored, dome-shaped, pearly, nonpainful but pruritic. Only cosmetic usually but scratching can lead to bleeding, secondary infections, scarring or autoinoculation of the skin or eyes |
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How do you treat MCV? |
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ablation (cut, freeze, etc.) |
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MCV is particularly prevalent in what patient population? |
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HIV patients |
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What is the histology of MCV? |
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epithelium has a craterform indentation with inverted lobules of kartinocytes-cytoplasmic eosinophilic inclusions (molluscum bodies) are diagnostic |
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T/F Removal of molluscum contagiosum virus can be accomplished by careful removal of the central core by expression with forceps. |
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true |
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What is monkeypox virus? |
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zoonotic poxvirus causing disease similar to, but milder than, smallpox that also causes lymphadenopathy. generally presents as fever, rahs, respiratory symptoms and lymphadenopathy. First identified in monkeys but much more common in rodents |