Lecture 29: Viruses Lecture outline 11/11/05 Types of viruses Bacteriophage Lytic and lysogenic life cycles viruses viruses Influenza Prions Mad cow disease 0.5 µm Figure 18.4 Viral structure of capsid Viral reproductive cycle Membranous envelope Head Tail sheath 18 250 mm 20 nm (a) Tobacco mosaic virus Entry into cell and uncoating of Replication (b) Adenoviruses Transcription Viral 70 90 nm (diameter) VIRUS HOST CELL Tail fiber m 80 200 nm (diameter) (c) Influenza viruses 80 225 nm Viral (d) Bacteriophage T4 Figure 18.5 proteins Self-assembly of new virus particles and their exit from cell 1
A capsid is the protein shell that encloses the viral genome of capsid 18 250 mm 70 90 nm (diameter) Head Tail sheath Tail fiber 80 225 nm Viral Envelopes are derived from the membrane of the host cell Membranous envelope 80 200 nm (diameter) 20 nm gure 18.4a, b (a) Tobacco mosaic virus (b) Adenoviruses Figure 18.4d (d) Bacteriophage T4 Figure 18.4c (c) Influenza viruses Bacteriophage Viruses of bacteria have been studied for decades T1, T2, T4 virulent Lambda temperate 5 Release (lysis) Phage assembly The lytic cycle of T4 1 Attachment. binds to specific receptor sites on cell surface. 2 Entry of phage and degradation of host. See the animation 0.5 µm Head Tails Tail fibers 4 3 Assembly of phage capsid Synthesis of viral genomes and proteins. 2
The lytic and lysogenic cycles of phage λ Phage Phage Attachment and injection of. Bacterial chromosome Phage circularizes This is a temperate phage Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Many cell divisions produce a large population of bacteria infected with the prophage. Viruses Classes of Animal Viruses Genome Type Viral coat Examples ds No Herpes, chickenpox Yes Smallpox ss no Parvovirus Lysis and release Lytic cycle New phage particles synthesized Certain factors determine whether or Lysogenic cycle Prophage Integrated into host chromosome. Replicates with host Viruses ds ss (serves as m) ss (template) ss (retrovirus) no no yes yes yes Tick fever Rhinovirus SARS Influenza Ebola Smallpox Influenza One of the few viruses with genome in segments (8) H5N1 nmhm.washingtondc.museum Spikes of hemagglutanin And neuraminidase 3
The reproductive cycle of an enveloped virus 1 s on the viral envelope bind to specific receptor molecules (not shown) on the host cell, promoting viral entry into the cell. Why are flu vaccines so hard to make? Envelope (with glycoproteins) 5 Complementary strands also function as m, which is translated into both capsid proteins (in the cytosol) and glycoproteins for the viral envelope (in the ER). 6 Vesicles transport envelope glycoproteins to the plasma membrane. Template m ER s 7 A capsid assembles around each viral genome molecule. 2 and viral genome enter cell HOST CELL 3 The viral genome (red) functions as a template for Viral genome () synthesis of complementary strands (pink) by a viral enzyme. proteins 4 New copies of viral genome are made Copy of using complementary genome () strands as templates. 8 New virus Flu strains are highly variable Recombination among the viral gene segments polymerase has high mutation rate Now have some antiviral drugs (e.g. Tamiflu) blocks the neuramidase enzyme so virus isn t released from cell 4
The structure of, the retrovirus that causes AIDS Only 9 genes in : Viral coat proteins Reverse transcriptase Integrase Protease Viral envelope Reverse transcriptase www.who.int/hiv/facts/en/ reproduction Membrane of white blood cell 1 Viral enters cell Reverse transcriptase 2 synthesizes from template. HOST CELL 3 Reverse transcriptase (two identical strands) Reverse transcriptase is a special polymerase Makes second strand. Viral - hybrid 4 Incorporated into host chromosome. 0.25 µm entering a cell NUCLEUS Chromosomal genome for the next viral generation Provirus 5 New viral is transcribed. 1. Copies from an template 2. Removes template m 6 New viral proteins are produced. New leaving a cell Virus 9 particles bud off. 8 New capsids are assembled 5
thymidine azt Protease inhibitorsanother class of drugs for AZT Protein in active site Inhibitor in active site Azidothymidine a modified thymidine The first anti-retroviral drug Stops synthesis because it does not have a 3 OH Originally developed as an anti cancer drug, but too many side effects initially produces one long polypeptide. Protease is necessary to cut the polypeptide into individual enzymes www.chemistry.wustl.edu/~edudev/labtutorials// Prions are infectious mis-folded proteins Prion Original prion Many prions Normal protein New prion Starts a slow chain reaction, causing regular proteins to assume the new shape Altered PRP proteins in nerve cells cause Mad Cow Disease 6