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An Introduction to the Viruses. Chapter 6. The Search for the Elusive Virus. ______________ postulated that rabies was caused by a virus (1884) Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s) 1950s virology was a multifaceted discipline
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An Introduction to the Viruses Chapter 6
The Search for the Elusive Virus • ______________ postulated that rabies was caused by a virus (1884) • Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s) • 1950s virology was a multifaceted discipline • Viruses: noncellular particles with a definite size, shape, and chemical composition
The Position of Viruses in the Biological Spectrum There is no universal agreement on how and when viruses originated Viruses are considered the most abundant microbes on earth Viruses played a role in evolution of Bacteria, Archaea, and Eukarya Viruses are obligate intracellular parasites 3
Naming viruses Classified based on structures, size, nucleic acids, host species, target cells. • 3 orders, 63 families, and 263 genera of viruses • Family name ends in -viridae • Genus name ends in -virus, Simplexvirus, Hantavirus, Enterovirus • Name of genus or family begins with description of virus • appearance: togavirus, coronavirus • place collected: adenovirus, hantavirus • effect on host: lentivirus • acronymns: picornavirus; (arbovirus)
Family – Herpesviridae Genus – Varicellovirus Common name – chickenpox virus Disease - chickenpox Examples • Family – Herpesviridae • Genus – Simplexvirus • Common name – herpes virus (Herpes simplex virus I (HSV-I) • Disease – fever blisters, cold sores
terminology • Virus = virus particle • ___________– fully formed, virulent, extracellular • ___________– host cell is lysed (broken) to release virions • ___________– viruses are inactive (latent stage) and host cell isn’t lysed (virus may be integrated within host genome)
Viral structure • ___________ (with spikes/receptors; 13/20 – derived from host cell) – may not be present • ___________ (morphologies: helical, icosohedral, complex) • Nucleic acid (DNA/RNA; ds or ss) • Matrix proteins (some enzymes)
capsids • Nearly all viruses have capsids- protein coats that enclose & protect their nucleic acid • Each capsid is constructed from identical subunits called capsomers made of protein – can self-assemble • ___________= capsid & nucleic acid • 2 types (based on shape): • helical • icosahedral
Envelope • If present, made primarily of lipids • ______________________ ; (ER, nuclear envelope, cell membrane-budding) • May be embedded with spikes for host recognition/binding
4 morphological types • Due to capsule shape and/or whether it’s enveloped • Helical • Icosahedral • Enveloped (with Hel. or Icos. capsid) • complex
Rod-shaped capsomers Coil around hollow center Nucleic acid is kept inside – wound-up within tube (nucleocapsid) Morphological types 1. Helical capsid
Morphological types Helical – capsid surrounds DNA like hollow tube Ex: TMV, influenza, measles, rabies (last 3 are enveloped)
Morphological types Tobacco Mosiac Virus Influenza virus
Morphological types 2. icosahedral • 20-sided with 12 corners • Vary in the number of capsomers • Each capsomer may be made of 1 or several proteins • Some are enveloped
Figure 6.7 Figure 6.8 19
Morphological types Human papilloma virus Adenovirus Herpesvirus Icosahedral – 3D, 20 sided
Morphological types 3. envelope • Naked viruses • Capsid proteins exposed to environment • Released from cells as cells ____________________ • Not a good pathogenic feature should keep host alive • Enveloped viruses • Covered with a lipid bilayer • ______________________ • Host cell keeps producing virus much longer sometimes for extended periods • Can bud off cell – thereby not destroying (lysing) it
Morphological types Enveloped vs. naked viruses
Morphological types 4. Complex viruses • Have additional or special structures • Examples: • ___________– lack normal capsid – instead, layers of lipoprotiens and fibrils on surface • ___________viruses have a polyhedral head, helical tail and fibers for attachment.
Morphological types Fig 6.9a,c
Nucleic Acids Viral genome – either DNA or RNA but never both Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses Number of genes varies for each type of virus – few to hundreds 26
Nucleic Acids DNA viruses Usually double stranded (ds) but may be single stranded (ss) Circular or linear RNA viruses Usually single stranded, may be double stranded, may be segmented into separate RNA pieces ssRNA genomes ready for immediate translation are positive-sense RNA ssRNA genomes that must be converted into proper form are negative-sense RNA 27
Enzymes important to replication Pre-formed enzymes may be present ___________– DNA or RNA ___________– copy RNA ______________________– synthesis of DNA from RNA (AIDS virus) 28
Life cycle Host range • Spectrum of cells a virus can infect • cell has to have a specific structure (receptor) on its surface for viral attachment • cell has to contain all of the enzymes and materials needed to produce new virions • May be one species or many • HIV (only humans) vs rabies (many animals) • Bacteriophages – tend to be very specific • May be one tissue or many within a host • Hepatitis (liver) vs polio (intestinal & nerve cells)
DNA replication in viruses * Uses host machinery!*
Viral Multiplication – animal viruses ___________– binding of virus to specific molecule on host cell ___________– genome enters host cell ___________– the viral nucleic acid is released from the capsid ___________– viral components are produced ___________– new viral particles are constructed ___________– assembled viruses are released by budding (exocytosis) or cell lysis
1. Adsorption and Host Range Virus coincidentally collides with a susceptible host cell and adsorbs specifically to receptor sites on the cell membrane Spectrum of cells a virus can infect – host range ___________– human liver cells ___________– primate intestinal and nerve cells ___________– various cells of many mammals 35
1. Adsorption to host cell membrane • Coronavirus with envelope spikes • (b) adenovirus (naked capsid) with surface capsid spikes 36
Entry: (2. penetration & 3. uncoating) Entry (viruses withenvelopes) • first must attach to cell membrane using receptors -- usually specific for host AND cell type • After adsorption _________ of membranes – (like two soap bubbles) • leaves the capsid free in the cytoplasm Entry (viruses withoutenvelopes) • first must attach using receptors (specific) • if a match, then engulfment -- ___________ • capsid then in the cytoplasm but within a vacuole • virus must uncoat without the genes being degraded
Figure 6.13 • Entry of viruses into cells (penetration and uncoating) • Endocytosis and engulfment of herpesvirus; • Fusion of cell membrane with viral envelope (mumps)
Synthesis: Replication and Protein Production Varies depending on whether the virus is a DNA or RNA virus DNA viruses generally are replicated and assembled in the ___________ RNA viruses generally are replicated and assembled in the ___________ Positive-sense RNA contain the message for translation Negative-sense RNA must be converted into positive-sense message 39
Duplication and synthesis: viral replication (more details in Ch. 9) Transport of DNA/RNA to nucleus • most viruses must get genes to nucleus to survive • some integrate into host DNA (leads to latency) • may require conversion of RNA copy to DNA • some remain independent chromosomes Viral replication • some do direct copies of DNA->DNA or RNA->RNA • others use "reverse transcriptase" to do RNA->DNA conversion • then DNA->RNA using HOST enzymes • timing is important -- some replicate only late in the cycle, after all proteins are made
5. Assembly: Filling the capsid • Capsid proteins made in cytoplasm • DNA or RNA gets fills empty capsids • final modifications to capsid • to plug any holes from DNA/RNA entry • to mature the outer proteins
6. Release Two ways assembled viruses leave host cell: ___________– exocytosis; nucleocapsid binds to membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed ___________– nonenveloped and complex viruses released when cell dies and ruptures Number of viruses released is variable 3,000-4,000 released by poxvirus >100,000 released by poliovirus 42
Viral budding – picking up cell membrane upon exit Budding of parainfluenza virus Budding of HIV
Damage to Host Cell Cytopathic effects - virus-induced damage to cells Changes in size and shape Cytoplasmic inclusion bodies Inclusion bodies Cells fuse to form multinucleated cells Cell lysis Alter DNA Transform cells into cancerous cells 44
Figure 6.16 45
Persistent infections with viruses Persistent infections - cell harbors the virus and is not immediately lysed Can last weeks or host’s lifetime; several can periodically reactivate – ______________________ Measles virus – may remain hidden in brain cells for many years Herpes simplex virus – cold sores and genital herpes Herpes zoster virus – chickenpox and shingles 47
Persistent infections with viruses Some animal viruses permanently alter genetic material ________________ Transformed cells have increased rate of growth, altered chromosomes, and can become “immortal” tumors (cancerous or noncancerous growths) Mammalian viruses capable of initiating tumors are called _________________ Papillomavirus – genital warts/cervical cancer Epstein-Barr virus – Burkitt’s lymphoma HBV and liver cancer
Multiplication Cycle in Bacteriophages ___________– bacterial viruses (phages) Most widely studied are those that infect Escherichia coli – complex structure, DNA Multiplication goes through similar stages as animal viruses Only the nucleic acid enters the cytoplasm - uncoating is not necessary Release is a result of cell lysis induced by viral enzymes and accumulation of viruses - lytic cycle
6 Steps in Phage Replication Adsorption – binding of virus to specific molecule on host cell Penetration – genome enters host cell Replication – viral components produced Assembly –viral components assembled Maturation – completion of viral formation Release – viruses leave cell to infect other cells