Lecture 29: Viruses Lecture outline 11/11/05

• Types of viruses – Bacteriophage • Lytic and lysogenic life cycles – DNA viruses – RNA viruses • Influenza • HIV • Prions – Mad cow disease 0.5 µm

Figure 18.4 Viral structure Viral reproductive cycle VIRUS DNA Capsomere RNA Membranous Capsid Capsomere of capsid envelope DNA Head Entry into cell and Capsid Tail DNA sheath uncoating of DNA RNA HOST CELL Transcription Tail fiber Replication Viral DNA

Glycoprotein Glycoprotein mRNA 18 × 250 mm 70–90 nm (diameter) 80–200 nm (diameter) 80 × 225 nm Viral DNA Capsid proteins

Self-assembly of new virus particles and their exit 20 nm 50 nm 50 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4 Figure 18.5 from cell

1 A capsid is the protein shell Viral Envelopes are derived from that encloses the viral genome the membrane of the host cell Capsomere RNA Membranous of capsid envelope Capsomere DNA Head Tail DNA Capsid sheath RNA Tail fiber Glycoprotein Glycoprotein 18 × 250 mm 70–90 nm (diameter) 80 × 225 nm 80–200 nm (diameter)

20 nm 50 nm 50 nm 50 nm Figure 18.4a, b (a) Tobacco mosaic virus (b) AdFeingouvrieru 1s8e.s4d (d) Bacteriophage T4 Figure 18.4c (c) Influenza viruses

The lytic cycle of T4 Attachment. Bacteriophage 1 binds to specific 2 Entry of phage DNA receptor sites and degradation of on cell surface. host DNA. • Viruses of bacteria have been studied 5 for decades Release (lysis) – T1, T2, T4

• “virulent” Phage assembly – Lambda • “temperate”

0.5 µm

4 3 Synthesis of viral Assembly of genomes See the animation phage capsid and proteins. Head Tails Tail fibers

2 The lytic and lysogenic cycles of phage λ Classes of Animal Viruses Attachment and This is a “temperate” phage Phage DNA injection of Genome Type Viral coat Examples DNA. ds DNA No Herpes, chickenpox Many cell divisions Phage DNA produce a large population of bacteria DNA Viruses infected with the Phage circularizes Yes Smallpox prophage. Occasionally, a prophage ss DNA no Parvovirus Bacterial exits the bacterial chromosome, chromosome initiating a lytic cycle.

Lytic cycle Lysogenic cycle dsRNA no Tick fever RNA Viruses ss RNA no Rhinovirus Certain factors Replicates with Lysis and release determine whether (serves as mRNA) yes SARS Prophage host DNA or ssRNA yes Influenza (template) Ebola ssRNA yes HIV (retrovirus) New phage particles Integrated into host synthesized chromosome.

Smallpox Influenza

One of the few viruses with genome in segments (8)

“H5N1”

Spikes of hemagglutanin nmhm.washingtondc.museum And neuraminidase

3 The reproductive cycle of an enveloped RNA virus Why are flu vaccines so hard

1 Glycoproteins on the viral envelope Capsid bind to specific receptor molecules to make? (not shown) on the host cell, RNA promoting viral entry into the cell.

Envelope (with 2 glycoproteins) Capsid and viral genome enter cell • Flu strains are highly variable HOST CELL 3 The viral genome (red) – Recombination among the viral gene functions as a template for Viral genome (RNA) synthesis of complementary segments RNA strands (pink) by a viral Template enzyme. – RNA polymerase has high mutation 5 Complementary RNA mRNA strands also function as mRNA, Capsid rate which is translated into both proteins capsid proteins (in the cytosol) 4 New copies of viral ER genome RNA are made and glycoproteins for the viral Copy of Glyco- using complementary RNA envelope (in the ER). proteins genome (RNA) strands as templates. • Now have some antiviral drugs (e.g. Tamiflu) 6 Vesicles transport envelope glycoproteins to – blocks the neuramidase enzyme so the plasma membrane. 8 New virus virus isn’t released from cell 7 A capsid assembles around each viral genome molecule.

4 HIV The structure of HIV, the retrovirus that causes AIDS

Only 9 genes in HIV: Viral coat proteins Reverse transcriptase Integrase

Protease Glycoprotein Viral envelope

Capsid

Reverse RNA transcriptase (two identical strands) www.who.int/hiv/facts/en/

HIV reproduction 1 HIV Membrane of Reverse transcriptase white blood cell 2 Reverse transcriptase is a Viral RNA enters cell synthesizes DNA from RNA template . special DNA polymerase HOST CELL

3 Reverse transcriptase Makes second DNA strand. Viral RNA

RNA-DNA hybrid 4 Incorporated 1. Copies DNA from an 0.25 µm into host HIV entering a cell DNA chromosome. RNA template

NUCLEUS Chromosomal Provirus 2. Removes RNA DNA 5

RNA genome New viral RNA template for the next viral generation is transcribed. mRNA

6 New viral proteins are produced.

8 Virus New capsids are 9 New HIV leaving a cell particles bud assembled off.

5 thymidine azt Protease inhibitors- AZT another class of drugs for HIV Protein in active site Inhibitor in active site

• Azidothymidine – a modified thymidine • The first anti-retroviral drug • Stops DNA synthesis because it does not have a 3’OH HIV initially produces one long polypeptide. • Originally developed as an anti cancer drug, but too many side effects Protease is necessary to cut the polypeptide into individual enzymes www.chemistry.wustl.edu/~edudev/LabTutorials/HIV/

Prions are infectious mis-folded proteins

Prion Original prion

Many prions

Normal New protein 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