Lecture 29: Viruses 0.5 m

Lecture outline 11/11/05 Types of viruses Prions Bacteriophage Lytic and lysogenic life cycles DNA viruses RNA viruses Influenza HIV Prions Mad cow disease

Figure 18.4 Viral structure Capsomere of capsid RNA Membranous envelope Capsomere DNA Head Capsid Tail sheath DNA RNA Tail fiber Glycoprotein Glycoprotein 18  250 mm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm 20 nm 50 nm 50 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

Viral reproductive cycle VIRUS Capsid proteins mRNA Viral DNA HOST CELL DNA Capsid Figure 18.5 Entry into cell and uncoating of DNA Transcription Replication Self-assembly of new virus particles and their exit from cell

A capsid is the protein shell that encloses the viral genome Figure 18.4a, b 18  250 mm 70–90 nm (diameter) 20 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses RNA DNA Capsomere Glycoprotein Capsomere of capsid Figure 18.4d 80  225 nm 50 nm (d) Bacteriophage T4 DNA Head Tail fiber Tail sheath

Viral Envelopes are derived from the membrane of the host cell Figure 18.4c 80–200 nm (diameter) 50 nm (c) Influenza viruses RNA Glycoprotein Membranous envelope Capsid

Bacteriophage Viruses of bacteria have been studied for decades T1, T2, T4 “virulent” Lambda “temperate” 0.5 m See the animation

The lytic cycle of T4 Attachment. binds to specific receptor sites on cell surface. 1 2 Entry of phage DNA and degradation of host DNA. 5 Release (lysis) Phage assembly Synthesis of viral genomes and proteins. 4 3 Assembly of phage capsid Head Tails Tail fibers

The lytic and lysogenic cycles of phage  This is a “temperate” phage Attachment and injection of DNA. Phage DNA Phage DNA circularizes Many cell divisions produce a large population of bacteria infected with the prophage. Phage Bacterial chromosome Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lysogenic cycle Lytic cycle Certain factors determine whether Replicates with host DNA Lysis and release or Prophage New phage particles synthesized Integrated into host chromosome.

Classes of Animal Viruses Genome Type Viral coat Examples ds DNA No Yes Herpes, chickenpox Smallpox ss DNA no Parvovirus dsRNA Tick fever ss RNA (serves as mRNA) yes Rhinovirus SARS ssRNA (template) Influenza Ebola (retrovirus) HIV DNA Viruses RNA Viruses

nmhm.washingtondc.museum Smallpox nmhm.washingtondc.museum

Influenza One of the few viruses with genome in segments (8) “H5N1” Spikes of hemagglutanin And neuraminidase

The reproductive cycle of an enveloped RNA virus Capsid and viral genome enter cell 2 The viral genome (red) functions as a template for synthesis of complementary RNA strands (pink) by a viral enzyme. 3 New virus 8 RNA Capsid Envelope (with glycoproteins) Glycoproteins on the viral envelope bind to specific receptor molecules (not shown) on the host cell, promoting viral entry into the cell. 1 New copies of viral genome RNA are made using complementary RNA strands as templates. 4 Vesicles transport envelope glycoproteins to the plasma membrane. 6 A capsid assembles around each viral genome molecule. 7 Complementary RNA strands also function as mRNA, which is translated into both capsid proteins (in the cytosol) and glycoproteins for the viral envelope (in the ER). 5 HOST CELL Viral genome (RNA) Template proteins Glyco- mRNA Copy of genome (RNA) ER

Why are flu vaccines so hard to make? Flu strains are highly variable Recombination among the viral gene segments RNA polymerase has high mutation rate Now have some antiviral drugs (e.g. Tamiflu) blocks the neuramidase enzyme so virus isn’t released from cell

HIV www.who.int/hiv/facts/en/

The structure of HIV, the retrovirus that causes AIDS Only 9 genes in HIV: Viral coat proteins Reverse transcriptase Integrase Protease Reverse transcriptase Viral envelope Capsid Glycoprotein RNA (two identical strands)

HIV reproduction Viral RNA enters cell 1 HIV Membrane of white blood cell Reverse transcriptase synthesizes DNA from RNA template . 2 HOST CELL 3 Reverse transcriptase Makes second DNA strand. Viral RNA RNA-DNA hybrid Incorporated into host chromosome. 4 0.25 µm HIV entering a cell DNA NUCLEUS Chromosomal DNA Provirus 5 New viral RNA is transcribed. RNA genome for the next viral generation mRNA New viral proteins are produced. 6 New capsids are assembled 8 Virus particles bud off. 9 New HIV leaving a cell

Reverse transcriptase is a special DNA polymerase 1. Copies DNA from an RNA template 2. Removes RNA template

AZT Azidothymidine The first anti-retroviral drug a modified thymidine The first anti-retroviral drug Stops DNA synthesis because it does not have a 3’OH Originally developed as an anti cancer drug, but too many side effects

Protease inhibitors- another class of drugs for HIV Inhibitor in active site Protein in active site HIV initially produces one long polypeptide. Protease is necessary to cut the polypeptide into individual enzymes www.chemistry.wustl.edu/~edudev/LabTutorials/HIV/

Prions are infectious mis-folded proteins Normal protein Original prion New prion Many prions Starts a slow chain reaction, causing regular proteins to assume the new shape Altered PRP proteins in nerve cells cause Mad Cow Disease