Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Chapter 13: Viruses Viruses • Obligate intracellular parasites ─ Must use host cell’s machinery to replicate • Viruses contain nucleic acid (DNA or RNA) ─ DNA or RNA can be single- or double-stranded ─ Surrounded by a protein coat (capsid) • Some are enclosed by an envelope Figure 13.2 Figure 13.1 Viruses: Host Range • Most viruses infect only specific types of cells in one host species ─ Bacteriophages only infect certain bacteria ─ HIV only infects certain human leukocytes • Host range: the spectrum of organisms or cells that a given virus can infect ─ Determined by specific host cell attachment sites and cellular factors ─ First step in a successful infection: virus attachment to host cell ◦ Relies on chemical interactions between host cell and virus Viruses: Structure • Virion: fully developed infectious virus particle ─ i.e. nucleic acid in protein coat • Protein coat: protects viral genome from environment and acts as a vehicle for transmission ─ Capsid: protein coat ─ Capsomeres: protein coat subunits ◦ Type and arrangement specific to virus Figure 13.2 Viruses: Structure Figure 13.4a, b Complex Viruses Figure 13.5a Viruses: Structure • Some viruses have an envelope covering the capsid ─ May include spikes (carbohydrate-protein complexes) ◦ Helps in attachment to host cells ◦ Spikes are antigenic in animals Figure 13.3 Viral Taxonomy • Viral species: A group of viruses sharing the same genetic information and ecological niche (host range) ─ Common names are used for species ─ Subspecies are designated by a number Species: Human herpes virus-1, HHV 2, HHV 3 Viral Multiplication • Virions contain: ─ Genes for synthesis of new virions ─ A few (if any) enzymes it needs for early infection steps ─ Main concern: its own replication • Everything else is supplied by the host cell (polymerases, ribosomes, ATP, tRNA, etc.) • Bacteriophages: two alternative mechanisms for replication ─ Lytic cycle: Ends with lysis and death of host cell ─ Lysogenic cycle: Host cell lives with integrated viral DNA (i.e. recombinant DNA) Multiplication of Bacteriophages (Lytic Cycle) 1. Attachment Phage attaches by tail fibers to host cell (weak bonding) 2. Penetration Phage lysozyme opens cell wall, tail sheath contracts to inject the NA into cell 3. Biosynthesis Host cellular processes are halted; Production of phage NA and proteins takes over 4. Maturation Assembly of phage particlesvirions 5. Release Phage lysozyme breaks cell wall, virions released to infect other bacteria Figure 13.5a Lytic Cycle Bacterial cell wall Bacterial chromosome Capsid DNA Capsid 1 Attachment Sheath Tail fiber 2 Penetration Base plate Pin Cell wall Tail Plasma membrane Sheath contracted 3 Biosynthesis -synthesis of viral components - Host cell DNA is degraded Tail core Figure 13.11 Lytic Cycle, cont. 4 Maturation -Virions assembled Tail DNA What else can happen here? Capsid 5 Release -Host cell lysis Tail fibers Figure 13.11 Multiplication of Bacteriophages: Lysogenic Cycle • Certain phages are capable of “choosing” between a lytic cycle and a lysogenic cycle • Lysogenic cycle: Prophage DNA stably incorporated in host DNA ─ Prophage: phage DNA inserted into the host cell’s chromosome ─ Virus does not immediately take the cell hostage; it patiently hides and waits for a signal (UV, chemical) ◦ Prophage genes are repressed by phage-derived repressor proteins that bind to prophage operators The Lysogenic Cycle Figure 13.12 Consequences of Lysogeny • Phage conversion of the host cell: the host cell obtains new properties due to the presence of the prophage ─ Some toxins are carried by prophages: botulinum, scarlet fever, cholera • Specialized transduction Specialized Transduction Prophage gal gene Bacterial DNA 1 Prophage exists in galactose-using host (containing the gal gene). Galactose-positive donor cell gal gene 2 Phage genome excises, carrying with it the adjacent gal gene from the host. gal gene 3 Phage matures and cell lyses, releasing phage carrying gal gene. 4 Phage infects a cell that cannot utilize galactose (lacking gal gene). Galactose-negative recipient cell 5 Along with the prophage, the bacterial gal gene becomes integrated into the new host’s DNA. 6 Lysogenic cell can now metabolize galactose. Galactose-positive recombinant cell Figure 13.13 Multiplication of Animal Viruses Attachment Entry Uncoating Bacteriophages Tail fibers attach to cell wall proteins Viral DNA injected into cell Not required Biosynthesis In cytoplasm (Chronic Lysogeny infection) Release Host cell lysed Animal viruses Attachment sites: plasma membrane proteins Capsid enters cell Enzymatic removal of capsid proteins In nucleus or cytoplasm Latency Budding from PM or rupture of PM Table 13.3 Release of an enveloped virus by budding (envelope proteins) Figure 13.20 Influenza • Viral infection of the lower respiratory system • Chills, fever, headache, muscle aches ─ 50,000-70,000 flu deaths in the US per year • Strains classified by H and N antigens (spikes) Influenza • Hemagglutinin (H) spikes: attachment to host cells ─ H1-15 • Neuraminidase (N) spikes: to release virus from cell ─ N1-9 • Both used for identifying viral strains and vaccine production Figure 24.16 Influenza: Why aren’t we immune? • Antigenic drift: ─ Mutations in genes encoding H or N spikes ◦ Influenza (RNA virus) has a high mutation rate ─ Minor variations; may involve only 1 amino acid change ─ Allows virus to avoid immune recognition developed from previous infections ◦ Vaccines change each year • Antigenic shift ─ Major changes in H and N spikes ─ Probably due to genetic recombination between different strains infecting the same cell Influenza • Spanish flu of 1918 ─ This strain acquired a lethal mutation ◦ Mortality rate over 20X that of previous flu epidemics ─ Killed nearly 50 million people worldwide ◦ Killed at least 700,000 in the US ◦ WWI-related transportation likely aided its spread ─ Young adults had the highest susceptibility ─ Virus was able to infect lungs and cause viral pneumonia ─ Sequencing of this virus in 2005 determined the virus arose from an avian virus with 10 amino acid changes that led to the lethal phenotype “Some 1,600 persons died in Seattle during the next six months despite the closing of theaters and schools, the banning of public gatherings, and the widespread wearing of gauze masks.” http://www.historylink.org/db_images/Spokane_Knoll_1918.JPG Influenza • Influenza strain H5N1: Avian flu ─ Some birdhuman transmission at large bird farms in SE Asia ◦ 6 people died in 1997 ─ Major concern: this flu strain may develop mutations that allow human-to-human transmission ◦ A purely avian virus “looks” foreign to humans −i.e. We don’t have immunity ◦ Previous pandemic episodes involved the emergence of a completely new strain Influenza • Flu vaccines ─ Typically directed at three most prominent strains in circulation at the time of development ◦ New antigens must be identified by February ─ Vaccine production is slow ◦ Grown in egg embryos Flu vaccine production Vaccine manufacturers receive seed virus from CDC/FDA Seed viruses are injected into chicken eggs Several days JanMay Eggshell is broken; egg white collected to harvest viruses Multiple purification steps Chemical treatment to inactivate viruses June/ July FDA tests each manufacturer’s strains for purity and potency Three different strains are blended Aug. Vaccines are packaged for distribution and refrigerated Sept. Shipping begins Oct/ Nov Vaccinations begin Immunity takes about two weeks Latent and Persistent Viral Infections • Latent Viral Infections ─ Virus remains in asymptomatic host cell for long periods (analogous to lysogeny) ◦ Herpesviruses: Cold sores, shingles • Persistent Viral Infections ─ Disease processes occur over a long period, generally fatal ◦ Virions build up over a long period of time