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by: Cassie Koepp


Cassie Koepp
GPA 3.61


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About this Document

Class Notes
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This 8 page Class Notes was uploaded by Cassie Koepp on Tuesday October 13, 2015. The Class Notes belongs to BIOL 4190 at Louisiana State University taught by Staff in Fall. Since its upload, it has received 48 views. For similar materials see /class/222840/biol-4190-louisiana-state-university in Biological Sciences at Louisiana State University.

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Date Created: 10/13/15
Adenoviruses Adenoviruses were not recognized as distinct viral agents until relatively recently In 1953 they were isolated from epithelial cells in adenoidal tissue from children and from military recruits with acute respiratory distress Adenoviruses have a predilection for mucous membranes and are responsible for a wide variety of clinical illness ranging from mild upper respiratory diseases in children to large outbreaks of pneumonias in military recruits The adenoviruses are divided into two genera l the Mastadenovirus genus which includes all the mammalian adenoviruses 2 the Aviadenovirus genus which contains adenoviruses associated with birds Within the Mastadenovirus genus are the human adenoviruses which can be subdivided into at least 49 serotypesAdenoviruses are a frequent cause of acute upper respiratory tract URT infections ie quotcoldsquot and eye infections conjuctivitis Some characteristic features of Adenoviruses are Widespread in nature infecting birds many mammals and man There are 2 genera Aviadenovirus avian and Mastadenovirus mammalian Can undergo latent infection in lymphoid tissues becoming reactivated some time later Several types have oncogenic potential double stranded linear DNA genome 3640 kbp with a covalently bound terminal protein attached to both 539 ends Nonenveloped virions 6580 nm diameter with penton fibers extending outward from each vertex of the icosahedral capsid There are at least 49 human adenovirus serotypes which have been classified into subgroups according to various properties including the oncogenicity of viruses in newborn rodents Viruses belonging to subgroup A such as adenovirus 12 Ad12 induce tumours with high frequency and short latency while viruses from subgroup B such as Ad3 and Ad7 are weakly oncogenic Adenoviruses from subgroup C which includes the well studied serotypes Ad2 and Ad5 D E and F are nononcogenic Adenoviruses are known to transform primary rodent cells in culture and adenoviruses of subgenus A and B are oncogenic in newborn rodents Taxonomy Talnify Genus Type Species osts Adenoviridae M astadenovirus lHuman adenovirus C Vertebrates Aviadenovirus F owl adenovirus A Vertebrates Morphology Detailed three dimensional structural models of adenovirus particles have been constructed based on a combination of cryoelectron microscopy and Xray crystallography There are at least 10 proteins in the Adenovirus capsid Capsid proteins i anztinn Knnwn Functinns Hexon monomer t 1 1111 Penton base 1111a Assoerated wrtn penton base 11V Frbre 1V Core assoerated wrtn DNA amp penton base 1V1 Hexon mrnorpolypeptrde ivu Cor ivm Hexon mrnorpolypeptrde IX Hexon mrnorpolypeptrde TP Genome r ermrnsl grotern 12 n quott quot Wrtnrntne eapsrd r w w otheE kb w H A oorgonm at w t r each ofthe 12veetrees reeeptor The eore oftne pamcle contams atleast 4 proterns T17 rermrnsl Proterneovs1ent1y attaenedto the 5 ends of the genome strands twd r to nrstones nonrcovalently assoerated wrtn the genome formrng a chromatinrhke substanee M a small 4km protern whose location and funetron are notknown Genome Linear nonsegmented ds DNA 3038kbp size varies from group to group which has the theoretical capacity to encode 3040 genes Genome structure crosshybridization restriction map is one of the characters used to assign viruses to groups 7095 homology within groups 520 homology between groups 135quot Gmmr Fwy W Tammi I i an 39139 g ymtI 31 A B C C39B39A M u c a A Demure me AA i B C C39 The terminal sequences of each strand are inverted repeats hence the denatured single strands can form quotpanhandlequot structures 100140bp There is a 55kD protein covalently attached to the 539 end of each strand Replication Replication of all Adenoviruses is similar and occurs in the NUCLEUS Adenovirus replication in cells is very ef cient Lytic growth of adenoviruses results in a yield of approximately 10000 virions per infected OE i l2141 132 n cell after 3236 hour v1rus Event hfe39 eyele Adsorption Femwalsm Hacker Ma geiiqnlpi 9mm Replication is divided into Ea u Transwiplion FARM EARLY and LATE DNA Rep39ltealwn phases the latter de ned as mquot beginning the onset Of Law Transcriplmn gammy DNA replication Attachment to cells is W 32M 3quot 3 rather slow taking several Indum qn qrs phase popmsas blocked to39lIuhr le Ik Transpng Elgclcecj Hes cell Translation locked hours to reach a maximum Disrupuon M Cgtoskeleton Inlerf wn anlagomsm MHC Downreguhl39mn ENTRY INTO CELLS adenovlms flbre coat proteln however lntemallsatlon is more selecuve cytoplasm nucleus Plasma membrane A m Mk p m u uncoatedpamcle lnto the cytoplasm n hereupon llls convenedlnto avlrus DNAecell hlstone complex Gene Expression L ELB 7 L3 r quot m u as h 1 4 kg Rama E 39 39 k 39 539 Lsmm q Before and independently of genome replication immediate early and early mRNAs are transcribed from the input DNA Transcription of the Adenovirus genome is regulated by virusencoded transacting regulatory factors Products of the immediate early genes regulate expression of the early genes Early genes are encoded at various locations on both strands of the DNA lquotleftward strand and rquotrightward strandquot Multiple protein products are made from each gene by alternative splicing of mRNA transcripts splicing was first discovered in Adenoviruses Sharp 1977 1 Phase Genes Transcribed Immediate early lElA Early lElB E2A E2B E3 E4 some virion proteins lLate lLate genes mostly virion proteins The first mRNNprotein to be made lh after infection is E1A This protein is a transacting transcriptional regulatory factor whose precise mode of action is not known not a DNAbinding quottranscription factorquot but is necessary for transcriptional activation of early genes The protein is also capable of activating transcription from a variety of other viral and cellular promoters and shows no sequencespecificity rather a modification of the cellular environment The second protein made is ElB ElA ElB together and independently of other virus proteins are capable of transforming primary cells in vitro especially Ad5 Ad12 Transformation is quotA CHANGE IN THE MORPHOLOGICAL BIOCHEMICAL OR GROWTH PARAMETERS OF THE CELLquot which may or may not result in cells which are able to produce tumours in experimental animals NEOPLASTIC transformation DNA Replication 13 5quot 339 a rmqu m Au as primer 1 a new mum in 5 r 5 rm 396 539Hawzmnl 339 539 392 7 Adenovirus DNA replication has been studied extensively both in vivo and in vitro nuclear extracts At least 3 virusencoded proteins are known to be involved in DNA replication TP acts as a primer for initiation of synthesis Ad DBP a DNAbinding protein Ad DNA Pol l40kD DNAdependent polymerase The steps involved in adenovirus DNA replication can be summarized as follows First the viral genome is coated with DBP This protein reacts cooperatively with the cellular transcription factor NFI which binds to a recognition site within the origin of replication separated from the l 18 bp core by a precisely defined spacer region NFIII also binds at a specific recognition site between nucleotides 39 and 48 Proteinprotein interactions between NFI and pol and pTP and NFIII help recruit the pTPpol heterodimer into the preinitiation complex DNA replication is then initiated by a protein priming mechanism Late Transcription Assembly occurs in the nucleus but begins in the cytoplasm when individual monomers form into hexon and penton capsomers Empty immature capsids are assembled from these protomers in the nucleus where the core is formed from genomic DNA associated core proteins Although host cell macromolecular synthesis ceases earlier in the infection infected cells remain intact and do not lyse Unlike other viruses there is no specific pathway for virus release although prolonged infection will eventually lead to cell lysis Virus particles tend to accumulate in the nucleus and are visible in the microscope as eosinophilic crystals finclusion bodies These are thought to be the basis of latent infections reactivation is caused by accidental lysis of infected cells releasing virus particles from the nuclei effectively a reinfection More properly this type of mechanism of persistence is known as quotoccultquot hidden infection rather than quotlatentquot cf herpesviruses Adenoviruses are known to interact with other viruses notably defective Parvoviruses Adeno Associated Viruses SV40 has also been shown to act as a helper virus for Adenoviruses coinfection overcomes a late block to Adenovirus replication in certain cell types which are normally nonpermissive This may involve functional substitution of SV40 Tantigen for Ad DBP Infectious AdenoSV40 hybrids have been isolated by rescuing Adenovirus deletion mutants by superinfecting with SV40 indicating functional overlap between the two families Pathogenesis l Disease 39 At Risk Acute Respiratory Illness Military recruits boarding schools etc Pharyngitis 39 Infants I Gastroenteritis 1 Infants Conjunctivitis All Pneumonia lInfants military recruits lKeratoconjunctivitis All Acute Haemorrhagic Cystitis Infants Hepatitis llnfants liver transplant patients DISEASES i Respiratory infections Endemic respiratory disease The most common respiratory illnesses are pharyngitis tonsillitis and nasopharyngitis and the most common symptoms are fever cough sore throat tonsillar exudates and cervical adenopathy often accompanied by coryza catarrh myalgia and headache Transmission of endemic adenoviral strains occurs through respiratory and fecal excretion of the virus Acute respiratory disease ARD is an in uenzalike syndrome seen in military recruits The illness is characterized by a 341 day history of fever pharyngitis cervical adenopathy cough myalgia and diarrhea Adenoviral pneumonia Some infants and military recruits with respiratory adenovirus infections may develop pneumonia which can be fatal The clinical symptoms include fever cough dyspnea difficulty in breathing and wheezing ii Ocular infections Sporadic acute follicular conjuctivitis This benign conjunctivitis is the most common eye infection caused by adenoviruses It resolves completely in 10714 days Epidemic keratoconjuctivitis This syndrome is distinguished by its greater ocular morbidity its potential for chronicity and permanent visual impairment and the occurrence of epidemics Early epidemics occurred in industrial settings particularly in shipyards where ocular trauma predisposes the eye to infection more recently it has been seen in eyecare facilities and in Vietnamese refugee camps iii Other infections Meningoencephalitis Adenoviruses are rarely isolated from the cerebrospinal uid or brain but have occasionally been associated with aseptic meningitis 39 J 39 39 quot39 and J 39 quot i Most patients have some encephalitic component in their illness rather than a pure aseptic meningitis Gastroenteritis The enteric adenoviruses types 40 and 41 cause diarrhea in young children they are second only to rotaviruses as a major cause of infantile viral diarrhea Acute hemorrhagic cystitis This illness occurs almost exclusively in male children The syndrome is associated with several days of urinary frequency bladder pain and gross hematuria Replication of the virus appears to be in the bladder itself Vaccines Available vaccines use live nonattenuated adenoviruses administered as an enteric coated tablet which bypass the respiratory epithelium and only replicate once they reach the intestine This causes an asymptomatic infection of the gastrointestinal tract and results in a good neutralizing antibody response However the risk of spread of vaccine virus in immunized children has limited the largescale testing of vaccines against the common endemic serotypes l 2 and 5 which are associated with acute respiratory diseases


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