Viruses

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Viruses

• AP Biology
• From Ch. 18

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Structure of Viruses

• Genome enclosed in a protective coat
• Genome may be DNA or RNA
• Protective coat is protein - CAPSID

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Structure of Viruses

• Some animal viruses also have a membrane called a
  viral envelope that surrounds the capsid
• These membranes are derived from the host cell,
  but also contain molecules of viral origin.

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Viral Reproduction - Intro

• Viruses can reproduce only within a host cell.
• Obligate intracellular parasites
• Lack enzymes for metabolism
• Have no ribosomes for making proteins
• Packaged sets of genes
• ARE VIRUSES ALIVE?

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Viruses and Hosts

• Each different viral type can infect only a
  limited range of host cells
• May infect only a single species ONLY E.coli
• May infect a range of species
• Rabies infects mammals
• Also, viruses of eukaryotes tend to be tissue
  specific
• Cold viruses - upper resp. rabies nervous
  tissue

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Different Viruses
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Viral Reproduction Cell Entry

• Viral genome must gain entry into a cell
• Viruses identify their host cells by a lock and
  key fit between proteins on the outside of the
  virus and receptors on the cell surface of the
  host.

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Types of Viral Cycles

• There are two main types of viral cycles
• Lytic cycle
• Lysogenic cycle

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Generalized Viral Infection

• Viral capsid (or envelope) docks to receptors on
  surface of cell to be infected.
• The viral genome (DNA or RNA) is injected into
  cell.

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Generalized Viral Infection

• Once inside host, viral genome reprograms the
  cell to
• Copy the viral nucleic acid
• Manufacture viral proteins (components of the
  capsid, for example)

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Generalized Viral Infection

• If the genetic material is DNA
• The host cells own DNA polymerases replicate the
  viral DNA.
• If the genetic material is RNA
• The virus will have to do a tricky little extra
  step to make DNA from its own RNA genome. More
  later on this.

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Generalized Viral Infection

• Virus diverts hosts resources from host needs to
  viral reproduction.
• Nucleotides
• Enzymes
• Ribosomes
• tRNAs
• Amino acids
• ATP
• And more

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Generalized Viral Infection

• Once components are made (viral genomes and
  capsid components) they self assemble into new
  viral particles.

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Generalized Viral Infection

• Often, the cycle is completed when hundreds to
  thousands of viruses emerge from the host cell
• Cell is often destroyed in the process
• Some symptoms of human viral infections result
  from cellular damage and death also from effects
  of bodys response to this destruction.
• Those viruses that exit a cell are now able to
  infect other cells.

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Viral Cycles The Lytic Cycle

• The lytic cycle culminates in death of the host
  cell.
• Lytic Lyses Cell ruptures
• This happens when new viral particles are
  released from host.
• Virulent Virus a virus that reproduces by the
  lytic cycle

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Limitations on the Lytic Cycle

• Examples of defenses against viruses can be found
  in studying bacteria and phages
• Natural selection favors mutants with receptor
  sites that arent recognized by a phage.
• If a phage enters a bacterium, restriction
  nucleases (enzymes) may break it dow

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Limitations on the Lytic Cycle

• Restriction nucleases (enzymes)
• Enzymes that recognize and destroy foreign DNA in
  a bacterium.
• The bacterial cells own DNA is modified in a way
  that prevents attack by its restriction enzymes.

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Limitations on the Lytic Cycle

• Of course, natural selection also favors viral
  mutants that evolve resistance to these enzymes
• Parasite-host relationships are in constant
  evolutionary flux
• One continually tries to outwit the other.

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Limitations on the Lytic Cycle

• Finally, many phages (and other viruses, too) can
  check their own activity
• Instead of lysing their host cells, they coexist
  with them
• This is called the lysogenic cycle.

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The Lysogenic Cycle

• Replicates viral genome without destroying the
  host
• Temperate viruses viruses that are able to use
  both lysogenic and lytic cycles

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Lysogenic Cycle

• Example Lambda bacteriophage
• Lambda can enter an E. coli cell and immediately
  enter a lytic cycle OR it can enter a lysogenic
  cycle

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Lysogenic Cycle - Lambda

• Lambda DNA molecule is incoporated into the host
  cells chromosome
• It is then known as a PROPHAGE.
• One prophage gene codes for a protein that
  represses most of the other prophage genes.
• Thus the prophage genome is mostly silent within
  the bacterium.

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Lysogenic Cycle - Lambda

• If the virus (prophage) is dormant, then how does
  it reproduce?
• Each time the E.coli cell prepares to divide, it
  replicates the phage DNA as it is replicating its
  own DNA.
• Copies are then passed to daughter cells.
• A single infected cell can give rise to a whole
  population of infected cells.
• The virus propagates without killing the host.

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Lysogenic Cycle Lambda

• Phages in the lysogenic state CAN give rise to
  active phages that will lyse the host cell.
• The lambda genome must exit the host genome.
• Then lytic cycle proceeds
• Usually it is an environmental trigger that
  switches the phage from lysogenic to lytic
• Radiation or chemical

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Animal Viruses

• Animal viruses follow the basic schemes of lytic
  and lysogenic cycles but with many variations.
• Key variables in animal viruses include
• Type of nucleic acid of viral genome
• Presence or absence of a membranous envelope

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Viral Envelopes in Animal Viruses

• Viral envelope outer membrane outside the
  capsid.
• Generally a lipid bilayer
• Glycoproteins protrude from cell surface.

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Viral Envelopes in Animal Viruses

• Helps the parasite enter the host cell.
• Glycoproteins bind to specific receptor molecules
  on cell surface.
• Viral envelope fuses with hosts membrane.
• Transports genome and capsid into cell.

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Viral Envelopes in Animal Viruses

• After entering the cell
• Cellular enzymes remove the capsid
• Viral genome replicates and directs synthesis of
  new viral proteins including glycoproteins for
  new envelopes.
• ER of host makes these
• They are transported to cell surface.
• They are clustered in patches that serve as exit
  points for the offspring virus particles.
• New viruses bud from these points a lot like
  exocytosis
• Bottom line Viral envelope is derived from
  hosts own membrane.
• Does not necessarily kill the host cell unlike
  lytic cycle.

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Viral Envelopes in Animal Viruses

• Some animal viruses have envelopes made from
  NUCLEAR membranes
• Herpesvirus
• Genome is DNA
• Viruses reproduce w/in the nucleus using cell
  enzymes to replicate and transcribe DNA
• CAN become integrated into hosts DNA

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Provirus

• Provirus genome of an animal virus that becomes
  integrated into the host cells genome.
• Similar to bacterial prophage.
• Herpesviruses Once acquired, herpes infections
  (cold sores and others) tend to recur throughout
  life.
• Between episodes, provirus remains latent.
• Stress may cause provirus to leave hosts genome
  and become active results in blisters, active
  infections.

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RNA as Viral Genetic Material

• Large variety of RNA genomes among animal viruses
• Classified according to
• Strandedness of the RNA molecule
• Can be single or double stranded
• How the RNA functions in the host cell

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RNA as Viral Genetic Material

• Class IV
• Class V
• Class VI

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RNA as Viral Genetic Material

• Class IV
• Can directly serve as mRNA
• Can be translated into viral proteins immediately

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RNA as Viral Genetic Material

• Class V
• RNA genome serves as a template for mRNA
  synthesis
• RNA genome is transcribed into complementary RNA
  which serves as mRNA to make viral proteins
• This transcribed mRNA also serves as a template
  to make more viral genome RNA
• Virus uses an enzyme packaged with the genome
  inside the capsid to do all this.

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RNA as Viral Genetic Material

• Class VI
• Most complex cycle
• Newly made DNA integrates into host as a provirus
• RETROVIRUSES backward
• Genetic info. Flows in a reverse direction
• RNA gt DNA
• Retroviruses are packaged with a special enzyme
  Reverse transcriptase
• Transcribes DNA from virus RNA genome
• Hosts RNA polymerase then transcribes viral DNA
  into RNA molecules that can become
• mRNA to make viral proteins OR
• RNA viral genomes to be packaged into new virus
  particles

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HIV A particularly important retrovirus

• HIV is a retrovirus
• Causes AIDS

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Affects of Viruses in Animals

• Amount of damage a virus causes often depends on
  the type of tissue it infects
• Cold viruses infect epithelium of respiratory
  tract which efficiently repairs itself.
• Poliovirus attacks nerve cells which cannot
  divide and cannot be replaced.
• Symptoms like fever, aches and inflammation are
  usually due to the bodys own defenses fighting
  the virus.

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Vaccines

• Vaccine
• harmless variants of pathenogenic microbes
• Stimulate the immune system to mount defenses
  against the actual pathogen

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First Vaccine

• Against smallpox
• Consisted of cowpox virus
• Edward Jenner
• Milkmaids who contracted cowpox were resistant to
  smallpox
• Scratched a boy with a needle bearing fluid from
  a sore of a milkmaid with cowpox.
• Boy was later exposed to smallpox and resisted
  the disease.

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Why Did the Vaccine Work?

• Cowpox and smallpox are so similar that the
  immune system cannot distinguish them.
• Vaccination with cowpox virus sensitizes the
  immune system to cow/smallpox and if ever exposed
  to smallpox (or cowpox again), the defenses will
  be so strong that the virus will be overwhelmed
  before it can cause illness.
• Jenners vaccine DID have to cause illness in
  order to confer immunity. Modern vaccines
  usually do not.
• Fundamental of Immune System Once you have been
  made ill by a virus (or other microbe) you cannot
  be made ill by that same virus again. Immune
  system is sensitized and will recognize it.
• You never catch the same cold twice.

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Why Did the Vaccine Work?

• Jenners vaccine DID have to cause illness in
  order to confer immunity. Modern vaccines
  usually do not.
• Fundamental of Immune System Once you have been
  made ill by a virus (or other microbe) you cannot
  be made ill by that same virus again. Immune
  system is sensitized and will recognize it.
• You never catch the same cold twice.

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Cures for Viral Infections?

• Prevention Yes Vaccines
• Cures No
• Antibiotics work only on bacteria
• Some drugs have been discovered that interfere
  with viral nucleic acid synthesis
• AZT inhibits HIV by interfering with reverse
  transcriptase

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Emerging Viruses

• Viruses sometimes appear to come out of nowhere
• HIV
• Hantavirus
• Ebola
• New strains of influenza each year

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3 Processes in Emergence

• Mutation of existing viruses
• RNA viruses have a high rate of mutation
• No proofreading found in DNA replication
• May mutate enough to outwit immune systems of
  people immune to previous versions.

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3 Processes in Emergence

• Spread of existing viruses from one host species
  to another
• Hantavirus is common in deer mice
• Humans became exposed to lots of it in Southwest
  US in 1993 after unusually wet weather increased
  mouse food supply
• Lots of mice lots of mouse poop lots of viral
  particles in airborne dust.

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3 Processes in Emergence

• Viral disease from a small isolated population
• HIV was rare
• Many factors made it spread
• Affordable travel
• Blood transfusion technology
• Sexual promiscuity
• Intravenous drug use

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3 Processes in Emergence

• Bottom Line
• Emerging viruses are usually not new, but are
  existing viruses that expand host territory by
• Evolving
• Spreading to new host species
• Spreading to a larger population from a small one
• Many human practices today give viruses
  opportunities to find new populations
• Destruction of forests for cropland brings humans
  into contact with other animals that may host
  viruses capable of human infection
• New roads through remote areas connect previously
  isolated populations

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Viruses and Cancer

• Strong evidence that viruses cause certain types
  of human cancer
• Hepatitis B virus linked to liver cancer
• Papilloma viruses linked to cervical cancer
• Others
• Oncogenes
• Viral genes directly involved in triggering
  cancerous characteristics in cells.
• Trigger to cancerous state probably involves
  combinations of events.

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Plant Viruses

• Plants also get viruses
• Serious agricultural pests
• Can spread from external source OR
• From parent through asexual reproduction
• Once virus enters plant cell, it can spread
  through plant via plasmodesmata
• No cures most focus on reducing transmission
  and breeding resistant varieties of plants.

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Viroids and Prions

• Viroids and Prions are even simpler than viruses

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Viroids

• Viroids
• naked circular RNA
• infect plants
• Only several hundred nucleotides long
• Do not encode proteins
• CAN replicate in host cell using cell enzymes
• Somehow disrupt cell metabolism and stunt growth
  of plant
• LESSON A molecule can be an infectious agent
• Still, these are nucleic acid and we know they
  can replicate

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What About Prions?

• Infectious PROTEINS
• Cause several degenerative brain diseases
• Scrapie in sheep
• Mad Cow Disease
• Creutzfeldt-Jacob Disease in humans

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Prions

• QUESTION How can a PROTEIN, which CANNOT
  replicate itself be an infectious agent?
• Hypothesis prion is a misfolded form of a
  protein normally present in brain cells.
• When inside a brain cell containing the normal
  form of the protein it somehow converts the
  normal protein to the prion version
• Prions may repeatedly trigger chain reactions
  that increase their numbers

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Prion Diagram
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Where Did Viruses Come From?

• Between life and nonlife
• Natures most complex molecule OR
• Natures simplest form of life???
• How did they originate?
• Depend on cells for propagation thus likely
  evolved AFTER cells.

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Where Did Viruses Come From?

• Hypothesis Viruses originated from fragments of
  cellular nucleic acids that could move from one
  cell to another
• Evidence
• Viral genome has more in common with host genome
  than genomes of other viruses
• Most likely candidates for sources of viral
  genomes are plasmids and transposons
• Plasmids
• Replicate on their own and can be passed from
  cell to cell
• Found in bacteria and yeast
• Transposons
• DNA segments that can move from one location to
  another in a cells genome.