T4 bacteriophage infecting an E. coli cell 0.5  m

Science as a Process Research into tobacco mosaic disease led to the conclusion that the pathogen was smaller than a bacterial cell The pathogen was named virus Characteristics of viruses: Smaller than bacteria Not cellular Composed of nucleic acid and protein Obligate intracellular parasites

Comparing the size of a virus, a bacterium, and an animal cell 0.25  m Virus Animal cell Bacterium Animal cell nucleus

Infection by tobacco mosaic virus

Figure 18.4 Viral structure 18  250 mm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm 20 nm50 nm (a) Tobacco mosaic virus(b) Adenoviruses(c) Influenza viruses (d) Bacteriophage T4 RNA Capsomere of capsid DNA Capsomere Glycoprotein Membranous envelope Capsid DNA Head Tail fiber Tail sheath

Capsids and Envelopes Capsid =

Capsids and Envelopes Capsid = protein coat that surrounds the viral genome viral envelope =

Capsids and Envelopes Capsid = protein coat that surrounds the viral genome viral envelope = derived from host cell or nuclear membranes, it helps the virus invade

Viral Genome Double stranded DNA Single Stranded DNA Double stranded RNA Single stranded RNA A virus has only one of these types of nucleic acids

Viral Replication What are the possible patterns of viral replication? DNA --> DNA RNA --> RNA, where viral genes code for viral RNA and proteins (class IV and V) RNA --> DNA --> RNA; where viral gene uses reverse transcriptase to create a “provirus” in the nucleus that does not leave host cell…viral RNA and protein is also made (class VI)

Bacterial Viruses Which scientists used bacteriophages to prove that DNA was the hereditary material? Hershey and Chase What are the two mechanisms of phage infection? Lytic and Lysogenic cycles (of DNA viruses)

Lytic Cycle Virulent phage … example T4 phage Steps: 1. Attachment 2. Entry of phage DNA and degradation of host DNA 3. Synthesis of viral genome and protein 4. Assembly 5. Release … (host cell dies while releasing phages)

Lysogenic Cycle Temperate phage … example  lambda phage Steps: 1. Entry 2. Integration of viral DNA into bacterial chromosome creating a prophage 3. Bacterium reproduces normally copying prophage and transmitting it to daughter cells 4. Under certain environmental conditions, a switchover to lytic cycle is triggered Other prophage genes may alter host’s phenotype and have medical significance Ex. bacteria causing diphtheria is harmless unless infected by a phage…phage experiences a lysogenic cycle and prophage causes host cell to make a toxin that causes illness!

Bacterial Defense What defense do bacteria have against phage infection? Restriction enzymes (a.k.a.  restriction endonucleases) What do restriction enzymes do? They cut up DNA. The bacterial DNA is modified to protect it from the restriction endonucleases.

Animal Viruses What is the viral envelope? An outer membrane (outside of the capsid) that helps the virus to invade the animal cell. The invasion of the virus has the following stages...

1. Attachment 2. Entry 3. Uncoating 4. RNA and protein synthesis 5. Assembly and release

Herpes virus Consists of double stranded DNA Envelope derived from host cell nuclear envelope not from plasma membrane It, therefore, reproduces within the nucleus May integrate its DNA as a provirus (becoming like mini-chromosomes in nucleus) Tends to recur throughout lifetime of infected individual. Often triggered by environmental situations.

RNA Viruses Different classes of RNA viruses: single stranded range from class IV to class VI Class IV: invades as mRNA, is ready for translation Class V: RNA serves as template for mRNA synthesis Class VI: Retrovirus  RNA  DNA (using enzyme reverse transcriptase)  RNA

The structure of HIV, the retrovirus that causes AIDS Reverse transcriptase Viral envelope Capsid Glycoprotein RNA (two identical strands)

The reproductive cycle of HIV, a retrovirus Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. 7 The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). 6 The double-stranded DNA is incorporated as a provirus into the cell’s DNA. 4 Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. 5 Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. 3 Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. 2 New viruses bud off from the host cell. 9 Capsids are assembled around viral genomes and reverse transcriptase molecules. 8 mRNA RNA genome for the next viral generation Viral RNA RNA-DNA hybrid DNA Chromosomal DNA NUCLEUS Provirus HOST CELL Reverse transcriptase New HIV leaving a cell HIV entering a cell 0.25 µm HIV Membrane of white blood cell The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. 1

Reasons for success of HIV Has an envelope Creates a provirus which stays in the nucleus of the host cell Is an RNA virus…high rate of mutation

Viral Disease Some viruses have toxic components Some cause infected cells to release enzymes from lysosomes Recovery involves ability to repair damaged region of the body.

Vaccines / Drugs What are vaccines and how do they work? Introduce body to harmless or weakened strain of the virus, so that your immune system learns to recognize the virus prior to invasion Few drugs around to fight viruses, most interfere with DNA, RNA or protein synthesis Often mimic nucleosides that would allow for nucleic acid synthesis Ex. AZT  HIV replication acyclovor  herpes

Emerging Viruses HIV, Ebola, SARS, West Nile Virus, Influenza, Hantavirus From where do these viruses emerge? From mutated versions of current viruses Jump from current host to new host Move from a previously isolated region of the world

SARS (severe acute respiratory syndrome) (a) Young ballet students in Hong Kong wear face masks to protect themselves from the virus causing SARS. (b) The SARS-causing agent is a coronavirus like this one (colorized TEM), so named for the “corona” of glycoprotein spikes protruding from the envelope.

Viroids and Prions Viroids are naked circular RNA that infect plants Prions are proteins that infect cells (cause tangles of proteins in brain) Examples of prions seen in scrapies in sheep, mad-cow disease, and Creutzfeldt-Jakob disease (CJD) in humans Timeline of Mad Cow Disease Outbreaks How can a prion spread infection? Altered versions of proteins that can alter other proteins (altered protein is thought to be a result of a mutated gene) Or can be ingested by eating contaminated meats…

Figure Model for how prions propagate Prion Normal protein Original prion New prion Many prions

Viral Evolution How did viruses evolve? Because viruses depend on cells for their own reproduction, they most likely evolved after the first cells appeared. Possible link to mobile genetic elements. (transposons, plasmids) Much debate about viral evolution…lots to learn about viruses!