Class Note for BIOC 461 at UA
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Date Created: 02/06/15
Viruses LECTURE TOPICS Types of viruses RNA and DNA Virus assembly Simple TMV Complex T4 bacteriophage RNA viruses ReplicationInfection Strategies poliovirus Membrane Viruses Influenza A SARS West Nile Retroviruses RNA to DNA Avian flu mania Types of Viruses Nucleic acid Representative virus Approximate number of genes Singlestranded DNA Double stranded DNA Singlestranded RNA Doublestranded RNA pX174 phage Polyoma virus Adenovirus 2 T4 phage Vaccinia poxvirus 03 phage Rous sarcoma virus ETobacco mosalc VlrUS EPoIiovirus Elnfluenza virus Reovirus Some Other 88 RNA viruses Retroviruses SARS West Nile Hantavirus RNA Poliovirus Egypt 1500 BC RNA TMV Tobaco Mosaic Virus Local lesions The Tulip Folly JeanLeon Gerome 1882 39 Tulip Breaking mosaic virus Tulipomania in Holland 1630 s One bulb starts centuries of industry Tulipomania muttezl h nFLtQR39Ar Vertmz39mdb Grond lijckie RedenS ndexfpekinge wmdm V HANDEL DERquot LORIS 1EN an 11min up eelpquck nan Anthonius He Guevara Emvoer cbrich eerl39jck man fal alrijt meet gheduiden 39 Clan rva 39cn ii39amm garish magi31mm hugely Uyt39hazt ruytfmaed I No ch ishier bygevoegz d Lii c van ecnigf 1 quan vcrcochr aende m 39 em Manner op den I thrgaru 1637 Item t Lei dick wan Cafliqr overd Goddmnc P Lu mum 1 alighgmkt plog merm m 113 mnemucmgw Angie x6 5 Warning Don t buy or sell tulips Dutch pamphlet 1637 l rlaJ In Mu A L 53955 nag non to 39 llr it m The Viseroij tulip sold 1637 for the equivalent of 2000000 US 2003 RNA Rabies virus Iraq 13th Century AD K m fquot a 11 f MWJJ lkvaJgJu F U 39 f by J 931 pas J 139 A Mi 4 E th ip g 5 4 L jiuwzbm ug39 sL gl 39155 A L L c acu ww QL 1E AVJM 51 gtJ kgjdyaub vjmb Translation ds DNA Smallpox virus cowpox Jenner 1798 E a WW n fw ugg 23 mlPaojf 7 o39r Mr MllLt l 171 13quot offIRA r 1 Cartoon 1802 Shogun Yoritomo victorious over smallpox art is 19 Century Smallpox was eradicated in 1977 last naturally occurring case in Somalia RNA TMV Tobaco Mosaic Virus Selfassembles A simple virus 1 RNA 1 protein Might expect assembly to start at one end and zip up to other end But Why 2 RNA tails on assembling firecrackers gt K quot3 70P0 gt gt0 w mmcgtnccmgtmcmcc 1 l m washers 2 5 end is pulled through center hole as lock O O O m H 390 O H 2 3 m 1 D m 0 O D 0 about 1000 bases from 3 end of RNA 1 Assembly starts at an internal RNA hairpin TMV Assembly is complex dsDNA Bacteriophage T4 is more complex Assembles in a strict sequential order T4 scaffold proteins and proteases assist assembly l 7 39 81416 749 50 64 65 lspnmanms l nu genes required A m u I w RNA virus replication strategies and refer to sense of RNA in virus particle RNA i RNA Class 2 Rabies virus Vesicular stomatitis Class 3 virus Reovirus RNA gt RNA gt mRNA 93 DNA 9 DNA lt RNAE Class 1 5 Class 4 Poliovirus E Retroviruses QB phage RNA is a translatable mRNA RNA must be copied to to be translated Poliovirus RNA gt RNA gtmRNA A 5 5 5 3 1 2 strand gt 3 gt template Polio RNA polymerase 339 339 539 339 539 5 quot strand strand o h 39lllll IIIIIIIII 39039 0 For new virus or for E ranslation to 5 viral proteins I Rephcatlve i S 0 3 Intermediate strand wands 9 quotIIquot Poliovirus nucleocapsid structure selfassembles Mature virus Protein coat structure is icosahedral Poliovirus RNA codes for a polyprotein that is cleaved to form 1 RNA replicase 2 Protease some other proteins 3 Proteins for mature virus nucleocapsid I 7500 bases A OH 3 mRNA 39quot 39VP39 39391 1 0 P2 P3 1 I Capsid proteins l Replicase proteases and other proteins COO Mature virus Membrane viruses Semliki Forest Virus ss RNA Membrane virus infects cell by receptormediated endocytosis Micrqwllus 3 Cell and viral Endnsome membrane fuse 793th 30315 pit vesitla Fusinn ol wral Elaclmn of and andusumal nuclaocapsid membrane 51 Virus parli le Membrane virus buds from cell membrane Creates new virus that has cell s membrane as a coat containing virus proteins and a nucleocapsid inside 1Irv39iral Host spike motein protein Cell mem bra na Cytoplasm Nuclfeoca psid What type of viru this hub bilayar West Nile Virus RNA 11kb Up d bilayar m 7 L West Nile Virus in Arizona and Pima County end of Summer 2003 mm D Hm 0 mm A an I wwwth a cum I u E 3 Ramquot I we mum r Name 0 Manama A aw IWNvm muv mr a mum I m 2 H umln leE What type of virus is this J A A L 741 5 VJ y TL Willi SARS coronavirus SARS coronavirus genome RNA Longest RNA virus genome 29736 bases 35nd Javaam pill gamma a 3 g Siljna i DM HHI HfFm W4 39 m 3m W mi m 39 WarWEE an away In Emma mpquot 1 mu 9 Emilia LEE awmama EELS l n Lama my ELK n1 mitt hm n u I71 5 Nil gmm m cm am dd 91 cm I 1135 39 39 quot gt 39 39 1171 SIRE Em HHS ha Vietnam Singapore 37 mm 34 new 21 close contacts 37 close conlans Beijing April 23 2003 urxlkuna lul l w mamasan n mlinuluz mmnmmmu an mm H hiiwl 39nu us want mum nunwwvammm x x J as a quotx 1 HA Reservoir hosts are bats not cats m p 39 in n rs n a K I 0 EBU EU J rews s Black flying fox T F39I39lllTES W Influenza A in art Grippe French from khrip Russian drift variant 1m Ikmudm Annm quot Paris gripp Paris grippe one of a series of lithographs of Parisian life by Honor Daurnier 1808 1879 documents the famil iar results of in uenza A antigenic drift Influenza A Virus A membrane virus nu sulk mu cleavagt Hemagglut In 39 I I r Smlk lmhhull IuILHNuuu Uphl 7 Amunhmlle of irult mum Sialic acid reccpmr binding Site Protease cleavage Fibrous sue lale viral assembly 5mm Small globule anchored lhrough membrane Lipid membrane of virus paniclc I Membrane protein M RNAs 8 d fferent ones Lipid bilayer 500 A 50 nm Influenza A Virus A membrane virus Virus and endosome Cell entry by endocytosis of a virus particle Virus protein in cell membrane New virus nucleoprotein capsid coated by Glycoproteins cell membrane Influenza A Hemaglutinin mutations m and do lead to loss of immunity conferred by vaccine each year 0 Epiiopc quota Antigenic drift v siaumm T Influenza ggggggzgsm Epitope Hemaglutinin is Epiwpei 610mm highly mutable at E 15ng sialic acid receptor binding sites Fibrous stem interface Antigenic drift Li pld membrane Neuraminidase also Is ofviruspanicle highly mutable at sialic acid cleavage sites Anchor Influenza A Hemaglutinin mutations m and do lead to loss of immunity conferred by vaccine each year Active site Antigenic for sialic Neuraminidase also acid cleavage is highly mutable at sialic acid cleavage sites r Stalk anchor Lipid membrane of Virus particle l l l The trivalent influenza vaccine for the 20052006 season includes ANew Caledonia2099 H1N1like virus AICalifornia72003 H3N2like virus BShanghai3612002Iike Virus Sleeping with the Enemies Influenza A infects man birds pigs horses other Influenza A In uenza A chromosome number Chromosome number 39 in Migrating birds are a source of global transmission Infection of the same cells by human and duck m uenza A quotquot585 Progeny in uenza A viruses can contain up to 256 combinations of differeni chromosomes from the human or duck viral RNA genomes An example of an in uenza A virus selected for growth in nonimmunized humans pandemic strain New combination of RNAs A new virus strain antigenic shift variant 3992 1918 Spanish flu pandemic killed 20 million people 1919 same flu killed 20 million more Accounted for 80 of US Army deaths in WWI The conscqtmncm ul39 anligcnic slli l918 New combination of RNAs Die Familie Egon Schiele 1917 In 1918 Edith died within 48 hrs 6 mo pregnant Egon died 4 days later 28 yrs old Influenza A pandemics and predominant strains H mm humans pigs 1The reintroduction of H1N1 in 1977 resulted in two Vi ruses presently circulating in the population but did not cause a pandemic Influenza A pandemics and predominant strains Genetic drift vs shift variants New flu strain appears in human population gt M 11957 19 1995 EMS I up Pandemic Influenza A pandemics and predominant strains P I a O I 39 i l I 1 kg 39 t I I H 1 o i i 39 I g I Avian flu threat Influenza A is spread by migratory birds along major global flyways East Asia I Amtrak Pacific r 013 if mack mg H w I 311 z Avian flu prevention Avoid sneezing chickens Vm mmmmm 39 lll li i ximlll ll 39linl m Il llt EElla l 2EmlllwnXl IansuEminmmumtmszallgu M m i l h ws mai 39 NHQImKNIIZEH39I mIZHRIE M IMI smlm m i39 Hl m m ml l mllill39gl li uli l WII39 W l l asksin nom 39Islnmtu magmas7m IWIZ ii EI 3 NHquot EHl l v wil I39 lEEa w li m u39 l lil l l lww ilwn llm w w gunmanu KM39E ME Iii ik39 m ni l n mm amnnn 39 El wi mlr aassnnnamgaxaaxauxsl lmlll lmllmr lli llr w ilmllmllizulr l AAkk lml39liw AEEWl t39R lw s Alumnaannaam awglann llllmlx ll znwzgll l l I lmlme ilalIr milm ulwiA IZIRL39 an almtsxnunnuwannllzi l lzll llzlu l lm Mml lal llw Mmk llm l Manamaluzig unnmwzulsi wussmwa azml i ll l 39 lenEm ISEzll klk f l Mml l lm l MW ll E i w lllllllnllil IUIElBlllml l a mma ni Ii i um x vi rlENsml munaramAnIvsImaaiimmvaw lan nu lE ukgt IAllli m ElkRI ml tunmum nzmm u NMM 17A E v m39z iMMIMI IIERE IHHIIH ia HEHXIIIEEanla l iiklv ix irla xlIQIIW iw lgnauwlxavamnnngwmlnusx aagnwnu XilAHEInIEHEINW snuallmu Vnmnt mxwawm 7 mamliwllmnl mammuslzziu EIRaIl39klAHEHIIKIE39AEAm QXIE 39E ll zna WI39 El 39imlgi HMI A HIE X EB ABI EE E i m5A Naw al l 27mii REil l SEEIRENAIERZIWw azn h nummikAwA2mwnu llil lll uw39 WHDINREVSS Cnllabnrating Laboratories Natiunal Summary 200304 4D 4E 44 4G uH3N H139l1anll CIH1H2 I3Llnubt39ped I E F39I39IEI391F39III1II39393 4E 50 5 1 3 5 F B 11 Week 13 15 1 15 5D 15 35 3D 25 2D 15 1U F39 an ant F39 c sit iv tiii39eeiil39yr Influenza Activity Estimates Reperted by State ii Territerial Epidemielegiete Week ending Nevemher 22 20113 Week 4 p He Hepart HI eijutrgr Spemdb Lceal Mixtry Regieral o iiltlidesp39eaiuziquot 39 39 39 I n n n I u I39 Virus Life Cycles and Infection Strategies Scenario 1 Infect make more virus polio flu Scenario 2 Tale of two fates A bacteriophage Scenario 3 Tale of a few fates retroviruses VIRUS LIFE CYCLE Scenario 1 Infect make more virus 1 2 3 4 5 6 7 Attachment Penetration Uncoating Transcription and translation Genome replication Virus assembly Virus Release VIRUS LIFE CYCLE Scenario 2 Bacteriophage lambda A life cycle A tale of two fates I39ll V quot Pragenn a l 31 DNA Lysed bacterium 3 i Adiuatig quot with released a i new 5L Ehaiel E cull Bacterial LYSOEEI39IiC 39 DNA cell partway El in DNA integrated in E calf genome Latent Scenario 3 HIV Retrovirus A tale of a few fates ds DNA genome provirus integrates in chromosome like A phage L Adsorption to I specific receptor 2a Penetration 2b Endocytnsis na 4 Reverse 3 U tating 7 111115ch 7 Translatttm I Double strand i 0f DNA 10 Release 5 Transport to nucleus u integration 7 8 Capsid assembly lt9 9 Budding LTR Retrovirus virion HIV RNA tumor viruses RNA genome two copies Lipid CHVCIOPC Receptorbinding protein env Transmembrane protein Gag proteins core Integrase Protease 39 39 Nucleocapsid Reverse transcriptase RNaseH DOII Retrovirus RNA tumor viruses oncogenic Avian sarcoma virus genome Reverse transcriptase oncogene Core proteins proteins in membrane Involved in replication Retrovirus reverse transcriptase Has 3 different enzyme activities III IZI Reverse RN H Reverse transcriptase ase transcriptase a a a 1st DNA strand Cuts RNA 2nd DNA strand Viral RNA DNA RNA DNA transcript Doublehelical hybrid of viral RNA viral DNA Retrovirus viral RNA genome 7 mm H RNA replication is complex URNAextended 2 HUM by 194952 Immsz use m lam mm x mpyuls39and ml gmm RNA 2RNasaHmuewy 1 mmuve hybndlmd RNA a Fursuump H mm nybumm wnh mman RNA 2 sequenuz a x a mm mm extended 5 Moswvmmmd RNA vemnued 9 a ray 3 39 ma ofsemnd DNA suan 1 Q synthemed s m Remammg mum RNA 3 s mmaved man a a 3 Sigma d 5 mmnim n 4 Ham 0 x s H 95333 a M dsDNA mmp emd Retrovirus RNA bdsDNA by reverse transcriptase Reverse transcriptase has 3 different enzyme activities 1 RNAdirected DNA polymerase 1st DNA strand 2 RNase H ribonuclease that removes viral RNA 3 DNAdirected DNA polymerase 2 1 strand DNA Product is a double stranded DNA copy of viral genome Inserts integrates into chromosome uses viral integrase Retrovirus RNA tumor viruses oncogenic Avian sarcoma virus genome Reverse transcriptase oncogene Core proteins proteins in membrane Involved in replication Retroviral oncogenes Table 345 Retroviral oncogenes Class Oncogene Retrovirus QIYIroISIinelfinas39es k ab Abelson murine leukemia virus erbB Avian erythroblastosis virus AVian sarcoma virus Rous sarcoma Virus w rowth factors nu sis Simian sarcoma virus quot39Cir f if cto39r ruecoatgrsy erbB Avian erythroblastosis virus Guanylnu39c 39eotide Haras Harvey murine sarcoma virus binding proteins Kiras Kirsten murine sarcoma virus 2quot Nuclear proteins fos FBJ osteosarcoma virus quotIIquot39m39m39 myb Avian myeloblastosis virus myc Avian myelocytomatosis virus T T T Proteins coded Oncogene name Retrovirus Viral oncogenes code for variants of normal cell proteins protooncogenes that is involved in control of cell growth and division NH3 L Transmembrane helix Tyrosine kinase domain erbB protein gene is always on causes cancer cells to proliferate is a tyrosine kinase is a growth factor receptor COO HIV and AIDS LECTURE TOPICS HIV virus Life Cycle RNA Genome Regulation of HIV gene expression Relation to other retroviruses Transmisison of HIV and AIDS in humans HIV infection tafrges in humans Potential AIDS therapies Vaccine for HIV HIV mutation rates HIGH like transcription 10394 to 105 HIV virus attachment and entry into cell HIV virus particle New HIV v39rus buds from cell membrane REVERSE WANscxwmsE HIV genome pol en nef HIV2 p01 va env ENVELOPE PROTEIN 1 CELL MEMBRANE COREANDENZVMES PRECUKSOR CORE PRECURSOR DNA POLVMERASE 3 PROTEASE AND RIBONUCLEASE INTEGRASE Fates of HIV target cells umo HIV PARTICLE aunomc UNINFECTED VIRUS T4 CELL lNFECI39ED CELL synmlum MULTlNUCLEATED ClANT CELL A CWOTOXIC EELL NATURAL KILLER CELL cymmxlc CELL T CELL LFI HAL HIT INFECI39ED T4 CELL ViRJLiERQEEI IESWNI IQ ALDJS VLRUiLtiM 1 2i 3 4 5 6 7 E 9 Retrovirus m Slranu virus cDNA Integrated in genome membrane virus 211d m we polyprateins cf poliovirus high mutability of in uenza virus overlapping genes altemate splicing complex regula ion of guns expression 10 latent phase like lambda phage I active gene expression and virus production HIV therapies and vaccine possibilities can target any stage theoretically L Adsorption to specific receptor 23 Penetration 2b Endocytosis 4 Reverse 3 Uncoaling transcription 7 Translation Double strand of DNA 5 Transport to nucleus integration LTR 39 39 EL Capsid assembly 10 Release 9r Budding O 0 439 SUGAR 1 OH N 239VDEOXYTHYMIDVNE 339 VAZIDOZ39 339 DIDEOXWHVMIDINE AZT h V V OH H 2 DEOXYCYTIDINE 2 3 7DIDEOYXCYTIDINE ddC 99 o OH H 2 DEOXVADENOSINE 2 3 DDEOXVADENUSINE ddA O imminm A l redmd mxg
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