8 - Virus Structure Multiplication
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 8 - Virus Structure Multiplication 8 - Virus Structure Multiplication Presentation Transcript

  • Viruses: Their Structure and Replication
  • What are Viruses • Small, Filterable, infectious agents – Cannot be seen by light microscope – Electron Microscope • Obligatory Intracellular Parasites – Not enough ATP by itself
  • Characteristics Of Viruses • Genetic Material: DNA or RNA – never both! – Single stranded (ss) or double stranded (ds) – Linear or circular • Capsid – Protein subunits (shell) – Protect the genetic material – May be involved in cell entry • Envelope (required for entry if present) – Lipid, protein and carbohydrate – Protein: viral origin – Lipid, carbohydrate: host origin – Involved in cell entry (located outside the capsid) • Subunit Replication only – Assembled after parts are made (quick log phase) • NEVER contain enzymes for protein synthesis or ATP metabolism!! – Always appropriate the host cell machinery
  • Size of Viruses
  • Virus Classification • Based on Host Range (determined by specific receptors) – Bacterial Viruses (Bacteriophages) – Animal Viruses – Plant Viruses – Others – (amoeba, insects) • Based on genome structure – DNA or RNA (never both) • ssDNA viruses • dsDNA viruses • ssRNA viruses – Plus Strand (+RNA viruses) » Same – Negative strand (- RNA viruses) » Complementary – Retroviruses » Converted into complementary DNA, then into the cell for replication • dsRNA viruses – Linear or circular – Size • 2000 to 200,000 nucleotides
  • Virus Classification (cont.d) • Based on Shape – Polyhedral viruses (icosahedral -20 faces, 12 vertices) – Helical Viruses – Complex viruses • Based on Envelope – Naked viruses – Enveloped viruses • Based on Disease caused – Respiratory viruses – Gastrointestinal viruses – Sexually transmitted viruses
  • Viral Structure: Capsid Capsid = protein coat that encloses and protects the nucleic acid of a virus • Accounts for most of the viral mass • Composed of single or multiple proteins • Each subunit = capsomeres
  • Viral Structure: Envelope Sometimes, Capsid covered with envelope •spikes = carbohydrate-protein complexes (glycoproteins) that project from the envelope • Can be used to attach to host cell • Influenza virus causes hemagglutination – clumping of red blood cells by use of spikes Non-enveloped viruses/ Naked Viruses = viruses whose capsids are not covered by an envelope
  • An Enveloped Virus
  • Virus mutations and immunity When a virus infects a host cell: •Host immune system produces antibodies •Antibodies = proteins that inactivate the virus by reacting with virus surface proteins  Stops further infection Why you can get some viruses more than once: • Genes that code for viral surface proteins are susceptible to mutation • Antibodies can’t react with the altered surface proteins  infection • Ex) influenza; frequent mutations in its spikes Non-neutralizing antibodies do not inhibit function Neutralizing inhibits function
  • Viral Structure: General Morphology Capsid Structure determines shape: Helical Viruses = nucleic acid is inside a hollow cylindrical capsid with a helical structure • Rabies, Ebola viruses, Tobacco Mosaic Virus Polyhedral viruses = many sided; icosahedron is common with 20 equilateral triangles as sides and 12 vertices • Poliovirus, Adenovirus, herpes, others??
  • Viral Structure: General Morphology Enveloped Viruses = can be helical or polyhedral, but the capsid is surrounded by an envelope • Helical: influenza virus • Polyhedral (icosahedral): Herpes simplex virus Complex viruses = Complex structures; additional structures attached to capsids, combos of helical and polyhedral, may have several coats around nucleic acid • Bacteriophage, poxviruses
  • Virus Structure
  • Virus Taxonomy International Committee on Taxonomy of Viruses (ICTV) groups viruses based on: • Nucleic acid type • Mode of replication • Morphology Viral species = defined as a group of viruses sharing the same genetic information and host range • Viral species are given common names • Ex) human herpesvirus • The suffix –virus is used for genus names • Ex) Simplexvirus • Family of viruses is given the suffix –viridae • Ex) herpesviridae
  • Some Viral Families & Genera affecting humans
  • Some Viral Families & Genera affecting humans: Continued
  • Isolation & cultivation of viruses Our understanding of viruses comes mostly from bacteriophages, as they are easily grown on bacterial cultures • Liquid suspensions or solid media Plaque method for detecting & counting viruses: 1) bacteriophages are mixed with host bacteria and melted agar, poured onto petri plate with existing layer of solid growth medium 2) Top layer solidifies ~ one cell thick 3) After several rounds of infection, multiplication and lysis, bacteria surrounding the virus are destroyed  plaque
  • Bacteriophage lambda on a lawn of E. coli • Each plaque is from a single virus (theoretically) • Number of plaques can be used to calculate plaque forming units (PFU) in initial suspension
  • Bacterial Viruses • Bacteriophages • DNA and RNA viruses – ds and ss – Linear and circular • Important tool – Alternative to antibiotic therapy • Basis to study viral replication in host cells – Lytic cycle (lyses cell) – Lysogenic cycle http://www.youtube.com/watch?v=gU8XeqI7yts It is very easy to grow viruses in bacteria, so it another reason it’s an important tool Never marketed phage therapy because it doesn’t work too well
  • Lytic Cycle of a T-Even Bacteriophage 1 2 3 Figure 13.11 HAS TO BE A DNA VIRUS Only infects cells with specific receptors “syringes in”
  • 4 Figure 13.11 Lytic Cycle of a T-Even Bacteriophage Integrates genome into host genome
  • Steps for Replication • Adsorption • Penetration • Biosynthesis – Uncoating – Replication • Assembly • Release Memorize
  • Lysogenic cycle: bacteriophage lambda Prophage: DNA incorporated and now it will make bacteriophages DNA randomly pops off in lysogenic cycle then goes through lytic
  • Lysogeny: importance • Lysogenic cells are immune to infection by the same phage (but not to other phages) • Phage conversion = tendency of host cell to exhibit new properties when carrying lysogenic phage • Ex) Cornyebacterium diptheriae produces toxin only when carrying lysogenic phage  diptheria • Same is true for shiga toxin by pathogenic E. coli • Specialized transduction = since bacterial DNA is incorporated with phage DNA, adjacent genes on host DNA may remain attached when phage DNA is excised for initiation of the lytic cycle • Introduce foreign genes into a new cell’s genome Specialized transduction – horizontal gene transfer
  • Multiplication of Animal Viruses • Entry – Adsorption (not misspelled) • Sticks to the surface – Entry/ Penetration – Uncoating (if capsid goes in) • Replication/ Synthesis • Assembly/Maturation • Release – Affect on host cell DNA matures in the nucleus, RNA matures in the cytoplasm
  • Multiplication of Animal Viruses: Attachment • Attachment – Virus attachment sites • Spikes or capsid proteins – Receptor Sites • Proteins, glycoproteins on host cell membrane
  • Multiplication of Animal Viruses: Entry • Endocytosis – Pinocytosis (unseen) • Plasma membrane folds inward into vesicles – Receptor mediated Endocytosis (creates own vesicles) • Influenza virus • Fusion (membranes are the same) – Viral envelope fuses with cell membrane
  • Multiplication of Animal Viruses: Entry Above: Togavirus entering a cell through pinocytosis
  • Multiplication of Animal Viruses: Entry Above: Herpesvirus entering a cell through fusion
  • Multiplication of Animal Viruses: Uncoating • Separation of nucleic acid from protein capsid – Capsid digested by host enzymes – Viral proteins synthesized to uncoat • poxviruses
  • Replication/Biosynthesis/Maturation/Release: DNA viruses • Gene expression in most viruses – Stage specific – Temporal Cascade • DNA viruses – DNA shuttled to host nucleus – EARLY Gene transcription • Uses host RNA polymerase • mRNA shuttled to protein translation sites in cytoplasm • Viral Enzymes (proteins) shuttled back to nucleus – Viral DNA replication • Viral DNA polymerase replicates DNA – LATE gene expression • Uses host RNA polymerase • mRNA shuttled to protein translation sites in cytoplasm • Viral structural proteins Proteins shuttled back to nucleus – VIRIONS assembled, shuttled back to cytoplasm – Trafficked via ER, Golgi, to Cell membrane for release “Too much detail, I just need you to remember that some genes are expressed before replication, some are expressed after. It just depends on when it needs that expression.”
  • It’s acidity is what causes the endosome to fuse with the envelope and release the capsid budding
  • biosynthesis of DNA viruses example Back into nucleus
  • RNA viruses • Multiplication is same as that of DNA viruses except mechanisms of how mRNA is generated • Four nucleic acid types of RNA viruses • Single (+) strand of RNA • Ex) picornaviridae, togaviridae • Single (–) strand of RNA • Ex) rhaboviridae • Double stranded RNA • Ex) reoviridae • “Reverse transcriptase” RNA (retroviruses) • Ex) retroviridae +  transcription  - translation  + - strand makes message, so - stays - - Strand will make one part (like capsid) + will make other part (like the RNA) Prophage – bacteriophage DNA incorporated??? Provirus – any other virus DNA incorporated??? RNA polymerase is more likely to make errors than DNA polymerase
  • Avian Influenza Clinical Focus, p. 371 Antigenic drift – mutations in how it looks Antigenic shift – so many mutations, very virulent, no antibodies to fight it
  • Biosynthesis of DNA vs RNA viruses
  • Multiplication of Animal Viruses: Release Non-enveloped viruses = released from host through ruptures in plasma membrane  host cell death Enveloped viruses = the envelope develops around the capsid by budding: virus takes portion of plasma membrane as it pushes through it to extracellular space • Doesn’t immediately kill host cell
  • Budding: formation of the envelope
  • Viruses and Cancer Oncogenic viruses (cancer generating) = viruses capable of inducing tumors in animals (aka oncoviruses) • ~10% of cancers induced by viruses Oncogenes = parts of the genome that cause cancer when mutated; expressed at high levels in tumor cells Transformation = viral genetic material integrates into host DNA and replicates with it (like bacterial lysogeny) • Used by all oncogenic viruses Oncolytic – viruses that grow in and lyse cancer cells
  • DNA oncogenic viruses Herpesviridae •Epstein Barr virus causes infectious mononucleosis - remains latent in some throat and blood cells throughout life  various lymphomas (Hodgkin’s, Burkitt’s) Papovaviridae •all uterine (cervical) cancers are caused by human papillomavirus Hepadnaviridae (Hep B) & Flaviviridae (Hep C) •hepatitis B and C can cause liver cancer
  • RNA oncogenic viruses • ONLY the retroviridae family of RNA viruses cause cancer Human T-cell leukemia viruses 1 & 2 = cause adult T-cell (white blood cell) leukemia and lymphoma Mechanism of tumor generation: Viral reverse transcriptase generates the double stranded viral DNA (provirus) that integrates into the host chromosome • Changes in genetic material always put the cell at risk for tumor formation Know oncogenic viruses and diseases with them
  • Latent viral infections Viruses may infect host cells but cause disease only after a long period of time = latent infections All human herpesviruses can remain in host cells for a person’s lifespan, until reactivation: • Immune suppression (ex: AIDS) • Fever, sunburn (cold sores from herpes simplex) •Reactivation may never occur  no symptoms Chronic can be latent or persistant
  • Persistent viral infections Persistent (chronic) viral infections occur gradually over a long period of time • Infectious virus builds up over time, rather than appearing suddenly (like latent infections) • Typically fatal Example: Subacute sclerosing panencephalitis (SSPE) = a progressive, debilitating, and deadly brain disorder • Caused by immune resistant measles • No cure; may be managed with medication Remember this one
  • Figure 13.21 Latent and Persistent Viral Infections Peaks, looks like it will go away, then spikes (can be lethal)
  • Prions Prions = proteinaceous infectious particles • No nucleic acid, just purely protein • Cause infections diseases - neurological • Bovine spongiform encephalophathy (mad cow) • Creutzfeldt-Jakob disease (CJD) • Gerstmann-Straussler-Sheinker syndrome Run in families, indicating genetic component  not purely genetic:  Eating infected meat transmits mad cow  CJD transmitted via transplanted nerve tissue Only killed by formaldehyde, very resistant KNOW ALL PRIONS
  • Prion Diseases • Crutzfedt-Jakob • Kuru • Bovine Spongiform encephalopathy (mad cow) • vCJD http://www.beatricebiologist.com/2010/08/watch-out-for- prions.html
  • Plant viruses and viroids Plant viruses = similar in morphology and nucleic acid types to animal viruses Common crop viruses: - Bean mosaic virus - Wound tumor virus  corn and sugarcane - Potato yellow dwarf virus Must penetrate cell wall by: - Wounds - Parasites  Ex) aphids that eat sap Result = color change, deformed/stunted growth, wilting Only destructive
  • Plant viruses and viroids Infected plant spreads virus via pollen and seeds viroids = short pieces of RNA with no protein coat • Known to cause some plant diseases • Pathogens of plants only • Potato spindle tuber viroid Prions are only protein Viroids are only RNA
  • Some major plant viruses
  • DNA virus families Adenoviridae = cause acute respiratory disease (common cold) Poxviridae = cause skin lesion diseases • Pox = pus-filled lesions • Smallpox • Cowpox Herpesviridae = named after herpetic (spreading) appearance of cold sores • Genus simplexvirus (cold sores) • Genus varicellovirus (chickenpox) • Genus lymphocryptovirus (mononucleosis)
  • Figure 13.5b Poxviridae • Double-stranded DNA, enveloped viruses – Orthopoxvirus (vaccinia and smallpox viruses) – Molluscipoxvirus – Smallpox – Molluscum contagiosum – Cowpox
  • Mastadenovirus (adenoviridae) Herpes simplex virus (herpesviridae) DNA virus families
  • DNA virus families Papovaviridae = named for the papillomas (warts) polyomas (tumors) and vacuolation (development of cytoplasmic vacuoles) • Genus papillomavirus causes warts - HPV: cervical cancer and cauliflower-like growths in cervix - Vaccine: Gardasil • Polyomavirus diseases primarily affect the immunocompromised  tumors
  • DNA virus families Hepadnaviridae = named for their role in causing hepatitis and containing DNA • Only one genus  causes hepatitis B • The other hepatitis viruses (A,C,D,E,F,G) are RNA viruses Hepatitis = inflammation of liver • Hep B is similar to Hep C (an RNA virus) • Both transmitted through blood - Associated with intravenous drug use • Cirrhosis, liver failure, liver cancer • Vaccine for Hep B, no vaccine for Hep C!
  • RNA viruses Picornaviridae = small (-pico) and contain RNA • Single stranded RNA viruses Important genera: Rhinovirus = responsible for >50% of common colds Enterovirus = fecal oral transmission poliovirus, coxsackie virus (aseptic meningitis) Hepatovirus = only species in the genus causes Hep A • Fecal-oral transmission • Contaminated food or water • Primarily affects less developed countries • Replication: mucosa  intestine  liver • Symptoms: fever, nausea, diarrhea, jaundice • Prevention: vaccine
  • Togaviridae are enveloped (toga = covering) • Like picornaviruses, have a single strand of RNA Important genera: Rubivirus = only member is rubella virus • Part of MMR vaccination series • Rubella = (latin: little red) aka german measles - Itchy red rash - Swollen glands, fever • Transmission: respiratory droplets • Treatment: none, usually subsides in days - Less severe than measles (rubeola virus) RNA viruses
  • RNA viruses Paramyxoviridae = enveloped viruses with spikes • single stranded RNA viruses Important genera: Rubulavirus = contains the species Mumps virus • Transmitted by respiratory droplets • Was common before MMR vaccine (1960s) • Symptoms: fever, headache, muscle aches, tiredness - swelling of parotid (salivary) glands! - Orchitis = swelling of testicles (~30% of males)
  • RNA viruses Rhabdoviridae = bullet-shaped viruses with a single strand of RNA • ~150 viruses of vertebrates, invertebrates and plants Lyssavirus = genus that contains the species rabies virus • Transmission: animal bite • Salivary glands highly concentrated with virus • Spreads from muscle cells into CNS • Fatal if not treated prior to severe symptoms
  • RNA viruses Orthomyxoviridae = enveloped helical viruses with a single strand of RNA Influenza virus = three genera (A,B,C) that cause influenza, a contagious respiratory illness Symptoms: cough, sore throat, aches, fatigue and serious complications: - Pneumonia - Bronchitis - Worsening of chronic health problems TEM of H1N1 Influenza
  • Avian Influenza Clinical Focus, p. 371
  • RNA viruses Reoviridae = respiratory, enteric, orphan • Affect gastrointestinal system, respiratory tract • Double-stranded RNA viruses Rotavirus = genus in family reoviridae • Most common cause of severe diarrhea among infants and children  Fecal-oral transmission • 2009: included into U.S. recommended vaccination program by W.H.O. Stylized SEM: rotavirus
  • RNA viruses Retroviridae = reverse transcriptase viruses • Reverse transcriptase = uses viral RNA as template to produce double-stranded DNA • integrated into host chromosome  provirus - protected from host immune system & antivirals - Replicates with host DNA - Can be expressed to produce new virions and infect adjacent cells Human Immunodeficiency virus (HIV) • Infects immune cells, progresses to AIDS • No cure: hard to target latent infected cells
  • Retroviruses