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Viruses Not Composed of Cells Characteristics • Obligate intracellular parasites • Single type of nucleic acid • Protein coat • Envelope Two Forms • Extracellular form • Intracellular form Host Range • Can infect many hosts • Determined by attachment to host cell – cell wall, flagella/fimbriae • Receptor sites, or plasma membrane in animal cells Structure • Nucleic acid-core • Either DNA or RNA, not both • Follows central dogma of molecular biology – Genetic info flows from NA to protein Structure • Protein coat-capsid • Envelope in some virions – May or may not have spikes-glycoproteins Envelope • Acquire membrane when budding or pass through membranes • Advantages of lipid membrane • Lose infectivity when envelope destroyed Envelope • Host’s phospholipids & viral proteins • Disadvantage -damaged easily • Without envelope- naked viruses – More resistant to chemicals/ disinfectants Enzymes • Required early in infection process • Bacterial virus or bacteriophage – lysozyme • Lysis of cell and release of virions Enzymes • Some have own NA polymerase • RNA polymerase in some RNA virions • Reverse transcriptase in retro viruses – RNA dependent DNA polymerase • Neuramidases-release of virions Morphology • Helical • Polyhedral- shape of icosohedron-20 sides • Enveloped- usually spherical Morphology • Complex viruses – combination of helical and icosohedral – bacterial viruses-head and tail – poxviruses- several coats of protein Growth of Bacteriophage • Grow in suspensions of bacteria or in bacteria cultures on plate • Plaque method for counting Growth of Animal Viruses • Living animals • Embryonated eggs-influenza • Cell cultures-continuous lines CPE Cytopathic Effect • • • • • • Visible effect of viruses on cells Stop multiplication of cells Lysosomes release enzymes Inclusion bodies SyncytiumInterferons- CPE • Mark infected cells for destruction by immune system • Transformation-abnormal cells Multiplication of Bacteriophage • Lytic cycle: produces virions • T-even phages, virulent phages, on E. coli – ds DNA for over 100 genes-head – tail sheath-retracts – DNA moves from head into host – Lytic Cycle • Attachment stage (adsorption) – attachment site on virus with complementary receptor on bacteria cell wall – use fibers at end of tail as attachment sites – may attach to flagella or fimbriae Penetration • • • • • Injects DNA Tail releases enzyme lysozyme Tail core driven through cell wall Tail reaches cell membrane Capsid remains outside: uncoating Biosynthesis • In cytoplasm • Host protein synthesis is stopped • Uses host nucleotides and enzymes to synthesis copies of phage DNA Biosynthesis • Synthesis of phage capsid proteins • Uses host ribosomes and amino acids for translation Maturation • • • • • Assemble into mature phages Head assembled and packed with DNA Phage tails assembled from plates, sheaths, Each head attached to tail Then fibers are attached Release • Lysis of PM, cell breaks open • Virulent (lytic) phages One Step Growth Curve • One step growth curve • Always present are mutant bacteria with altered receptors Lysogenic Cycle • Temperate phages do not always under go lytic cycle: • Lysogeny• Phage NA incorporated into the host NA • Lambda phage in E. coli – Integrates into bacterial chromosome – Prophage Lysogenic Cycle • Prophage replicated along with host DNA • On rare event- can lead to popping out of phage DNA Lysogenic Conversion • Alteration of characteristics of bacteria • Cells are immune to reinfection by same phage • Not immune to infection by different phage Phage Conversion • Medical significance of conversion • C. diphtheriae and C. botulinum • Without prophage do not cause disease • Strep with prophage can cause scarlet fever Specialized Transduction Mediated by lysogenic phage ( only temperate virions) – DNA on either side of prophage can be picked up Phage lambda picks up gene for galactose fermentation-gal from host Carry this gene to new host which is gal negative Multiplication of Animal Viruses • Attachment – receptor sites on animal cells - proteins and glycoproteins of PM – sites are distributed all over surface of virus • Spikes or capsid Penetration • Trigger endocytosis-folding inward of PM-vesicle • Enveloped viruses also can fuse with PM – Fusion protein facilitates this – Releases capsid via endocytosis Uncoating-Removal of Capsid • Varies with virus • Separation of NA and protein coat – lysosomal enzymes inside vesicles • Some enzymes in host cytoplasm Biosynthesis of DNA viruses • DNA viruses replicate DNA in nucleus of host • Synthesize proteins in cytoplasm • Early transcription- for enzymes & proteins needed for viral DNA replication • Late transcription-capsid & structural proteins Maturation • Assembly of virus – Takes place in nucleus – Proteins transported via ER into nucleus • Released from host cell – Budding – Lysis Biosynthesis of RNA Viruses • Multiply in host cell’s cytoplasm • Picornavirus-polio, ss RNA, • RNA is a sense strand or positive since it acts as mRNA • Early translation-2 proteins – Inhibits host cell synthesis of RNA & protein – Produces RNA-dependent RNA polymerase Biosynthesis of SS RNA Virus Synthesizes another strand of RNAantisense strand or negative strand – Serves as template for all + strands • Late transcription and translation -proteins for capsids Rhabdoviruses • Rabies, bullet shaped • Contains a single minus strand and RNA dependent RNA polymerase – makes + strands from minus strand • + strand serves as mRNA for new viral RNA and for proteins Maturation and Release • Assemble capsids spontaneously • Enveloped viruses – proteins in envelope encoded by viral genes – envelope wraps around capsid -budding • Lipids and CH2O encoded by host cell • Noneveloped viruses released via rupture Retrovirus • HIV – Positive strand RNA virus – Own RNA polymerase – RNA dependent DNA polymerase – Reverse transcriptase – RNA to DNA Provirus • Viral DNA incorporated into host DNA – provirus • Never comes out of host chromosome • Protected from host’s immune system and antiviral drugs Retrovirus Replication • Provirus may remain in latent state replicating with host DNA OR • Provirus may be expressed and produces new viruses Consequences of Virus Infection • Lytic infection: destruction of host cell – Acute infection-influenza • Persistent infection : slow release of virions – Budding without lyzing cell Consequences of Virus Infection • Latent infections: delay between infection and lytic events • Transformation: change in cell Herpes Viruses • Large, enveloped, latent • Herpes type 1 and 2 – Cold sores, genital and neonatal herpes – Varicella zoster- chickenpox, and shingles • EBV-mononucleosis Herpes Viruses • CMV – Salivary gland virus-acute febrile illness, birth defects • Roseolovirus (6) – Infants with rash and fever • HHV-7 rashes in infants • HHV-8 Kaposi’s sarcoma Transformation • Normal cells become tumor cells – Benign and malignant • Oncogene-cancer gene Oncogenes • Genes always turned on – Continuous cell division • Activated to abnormal functioning by chemicals, radiation and viruses • Loss of control of cell cycle – Result in formation of tumors Oncogenic viruses • 10- 20% of cancers known to be virus induced • Oncogenic viruses incorporate into host DNA – Cells lack contact inhibition DNA Oncogenic Viruses • EBV- herpes virus, causes 2 human cancers – Burkitt’s lymphoma ( rare affecting children in Africa) – Nasopharyngeal cancer is worldwide • 90% of population carry latent stage of EBV in lymphocytes • Hepatitis B virus has casual role in liver cancer • Papilloma virus- can cause cervical & penile cancer-vaccine RNA Viruses • Human T cell leukemia viruses Prions • Proteinaceous infectious particle – Lacks nucleic acid • Degenerative changes in brain-large vacuoles – Dementia, wasting, & loss of motor control Prions-CJD • Modified forms of normal cellular proteins • Cause disease by converting normal protein into abnormal forms CJD • Transmission – Ingestion of contaminated food – Sporadic cases – Contaminated surgical instruments • Neural electrodes or forceps etc. Influenza • 8 segments of RNA as genome: minus strands • Protein capsid • Envelope with projections (virus can change these so it survives each year) Spikes • H spikes -hemagglutinin (binds to host receptors) – Recognize cells and attach • 100 N spikes -neuraminidase – Release virus from infected cell Influenza • Spread by droplets-use regular mask • HA bind to ciliated respiratory cells • Envelope fuses with PM and enters cells S&S • Release of cytokines • Incubation period- 1-3 days, spread day before symptoms • Ill 7-10 days Recovery • Spontaneous • Secondary infections • Death Strains of A Viruses • Strains H1,H2, H3; N1 and N2 • Antigenic shift-responsible for outbreaks – Reassortment Antigenic Shift (continued) • Genetic reassortment • 2 viral strains infect the same animal/human • Swine can be infected by both human & avian strains-mixing vessel Antigenic Shift (continued) • New virions released from swine • Must have a full complement of the RNA segments to be infective • May occur every 10 years or more Antigenic Drift • Minor annual variations in genetic make-up of HA or NA • RNA enzymes lack proofreading capability H1N1 Virus • Originated in swine • Virulence similar to seasonal influenza viruses • Humans have little or no immunity Healthcare Worker PPE • CAL OSHA requirement for H1N1 • Wear N95 mask –Must be fit-tested for mask –Wear a visor over mask –Wear gown & gloves Vaccination • Get vaccinated yearly • Seasonal vaccine –2 types of strains of A: H1N1 & H3N2 –1 B strain • H1N1 available Antiviral Drugs for H1N1 • Sensitive to neuraminidase inhibitors –Tamiflu –Relenza • Prevents virus from leaving cell • Benefit if started within 48 hours of illness onset Influenza Pandemics in the 20th Century Years Flu Virus Deaths 1918-1919 “Spanish” Type A (H1N1) 675,000 US 1957-1958 “Asian” Type A (H2N2) 70,000 US 1968-1969 “Hong Kong” Type A (H3N2) 34,000 US 2009 “Swine” Type A (H1N1) 8000 US Pandemic Influenza • Pandemic influenza virus – A new influenza A subtype can infect humans – Causes serious illness – Spreads easily from human-to-human H5N1 is a likely candidate, but is not a pandemic virus yet H1N1 is a pandemic virus AIDS • Final stage of a long infection with HIV – Attacks immune system – T helper cells and macrophages 2 Types • HIV 1-99% of all global cases • HIV 2 discovered in West Africa – Reduced virulence – Causes milder disease Structure of HIV • 2 positive strands of RNA • 2 identical strands of RNA enzyme- reverse transcriptase – Copies RNA into DNA • Envelope with spikes termed gp120glycoprotein of 120,000 mw Pathogenicity • Spikes allow attachment to CD4 receptors on host cells • Coreceptors on T helper cells needed also for attachment Fusion Protein • Fuses CM with viral envelope – Nucleocapsid enters cell – Uncoated to release enzyme and RNA Life Cycle • RNA plus strands used for template only • Viral DNA incorporates into host DNA Integrase enzyme (viral) joins viral DNA with cellular DNA • May be latent or cause disease Protease • • • • Another enzyme in viral core Budding virus is not mature yet Proteins in core are in one long strand Must be cut by protease then virus is infectious Mutations • Rapid antigenic mutations • Mutations at every position in genome many times each day AIDS • Progression to AIDS – based on T cell population • Progression from HIV to AIDS is about 10 years HIV Transmission • • • • • • Contact with infected body fluids BloodSemen Heterosexual sex fastest growing risk factor Drug use and multiple partners Mother to baby, breast feeding Treatment: Highly Active Anti Retrovirus Therapy • Nucleoside analogs-AZT etc. inhibit reverse transcriptase • Proteases- enzyme that cuts proteins into pieces reassembled into coat of new HIV particles • Integrase inhibitors- enzyme that incorporates viral DNA into DNA of host • Fusion inhibitors