Viruses (2006)

(23 February 2006)

(The ultimate in “selfish genes”)

Viruses are parasites

  • Cannot reproduce by themselves
  • Cannot make their own energy
  • Cannot make their own proteins

All forms of life have viruses

  • Animal viruses
  • Plant viruses
  • Bacterial viruses

Specificity of viruses

  • Only infect “their own” species
    • OR closely related species
  • plant or bacterial viruses don’t infect people
    • a FEW mammalian viruses do cross to humans
    • the closer the species, the more likely a mutation can let the virus cross

Living or Not?

  • Invalid question
  • Viruses are Pieces of us
    • Actually pieces of our genes
  • Is a heart alive? a brain?
    • When outside of a body, misses on most definitions.
    • When inside of a body, usually considered to be alive

What IS a virus

  • A small number of genes
  • Wrapped in a protective coat
  • With “receptors” on the outside

Viral genes

  • Can be DNA or RNA
    • In most things, DNA is like a library copy of the genome — very accurate, edited, and stable
    • In most things, RNA is like a Xerox copy — abundant, error prone, and easily degraded
  • Can be single or double stranded
  • Can be linear or circular

Examples

  • Herpes or Smallpox — dsDNA
  • Influenza — dsRNA
  • HIV — ssRNA

Viral protective coat

  • Most have a highly regular capsid
    • made of protein in a regular array
  • Some have a membrane envelope
    • made from host cell membrane
    • modified by the virus

Capsids (shells)

  • usually icosahedral symmetry or helical tube
    • sometimes highly modified
    • “bullet,” “cone,” “thread”
  • often many copies of one or a small number of different proteins
  • antigenic — recognizable by immune response
  • proteins on outer surface can act as receptors

Envelopes

  • surround the capsid
  • made of membrane lipids (fats)
  • richly studded with proteins
    • antigenic
    • act as receptors
  • fuse with cell membrane during infection

Viral Receptors

  • Usually proteins or parts of proteins on the outside of the virus (capsid or envelope)
  • Fit some cellular surface molecule like a lock and key
  • Interaction triggers a cellular response
    • engulfment
    • fusion
  • Give the virus its primary host range

Life Cycle of a Virus inside a Host

Viral multiplication: Several stages

  • It has to get across the cell membrane and into the cytoplasm
  • Get its genes into the cell’s nucleus
  • Send RNA into the cell’s cytoplasm to code for viral proteins
  • Assemble a new capsid with new copies of genes
  • Get out of the cell

Entry (viruses with envelopes)

  • first must attach to cell membrane using receptors — quite specific
  • if a match, then fusion — like two soap bubbles
  • that leaves the capsid free in the cytoplasm

Entry (viruses without envelopes)

  • first must attach using receptors (specific)
  • if a match, then engulfment — looks like phagocytosis
  • capsid then in the cytoplasm but within a vacuole
  • virus must uncoat without the genes being degraded

Transport of DNA/RNA to nucleus

  • most viruses must get genes to nucleus to survive
  • some integrate into host DNA
    • may require conversion of RNA copy to DNA
  • some remain independent chromosomes

Viral replication

  • some do direct copies of DNA->DNA or RNA->RNA
  • others use “reverse transcriptase” to do RNA->DNA conversion
    • then DNA->RNA with “normal” enzymes
    • timing is important — some replicate only late in the cycle, after all proteins are made

Filling the capsid

  • Capsid proteins made in cytoplasm
  • DNA or RNA gets from nucleus to empty capsids
  • Capsids fill (mechanism poorly understood, but can be spontaneous)
    • mostly know from bacterial and plant viruses
  • final modifications to capsid
    • to plug any holes from DNA/RNA entry
    • to mature the outer proteins

Attaching the envelope

  • capsid moves to inner surface of cell membrane
  • viral proteins accumulate in cell membrane in that spot
  • bleb forms and begins to surround the virus
  • eventually the bleb contains the capsid and breaks off as a full “vesicle”
  • the opposite of engulfment

Release of the virus

  • enveloped viruses just keep blebbing (budding)
  • non-enveloped are less understood
    • some just lyse the cell and release the accumulated virus
    • others can bud out, but mechanism is unknown

Survival Outside the Host

Some viruses are tough

  • can survive drying
  • can survive high and low temperature
  • can survive detergent, acid, alkalai
  • partly because of protein shell (capsid)
  • partly because of lack of water

Some viruses are not tough

  • enveloped viruses are usually more vulnerable
  • membranes are very sensitive to detergents
  • sometimes quite sensitive to drying
  • even sensitive to oxygen

Most viruses can survive longer than their host

  • if host dies, virus can remain viable in free state
  • can also stay in blood or tissues of dead host
  • can be passes from host to host before death
  • numbers are on their side
    • single host can make trillions of virus copies or more!

How can we fight viruses

  • immune system is our only defense
  • drugs are rare because “viruses are us”
    • most drugs that kill viruses, kill us too
    • even those that are “specific” for viruses are not harmless to us.

Immune response

  • all viruses have specific receptor proteins on their surface (and often many other proteins)
  • all viruses are recognized by the immune response
  • within 10- 14 days a primary immune response is raised and we can begin to eliminate viruses as foreign invaders
    • many viral diseases last about that long

Viral defenses against immune response

  • fast action and transmission before immune response can be raised
  • hiding inside cells
    • e.g. herpes — chicken pox and shingles
    • HIV
  • if virus is budding, then infected cells have new proteins on surface and immune response kills them

Best defense against immune response?

  • Stop viral replication
    • hide genome in host genome but don’t make anything
    • no antigens, no immune response
  • Get from cell to cell quickly
    • as soon as “free” virus around, immune response will see it an begin to clear it
  • for HIV, kill the immune response!

Some examples of viral diseases

  • Flu
  • Smallpox and measles
  • HIV
  • Colds (dozens of different viruses)
  • Herpes (chickenpox, cold sores, genital herpes)
  • hepatitis

Differences between viruses and bacteria

  • bacterial are complete organisms
  • bacterial evolution was separate from animals (so many functions are different, making them targets for drug therapy)
  • bacteria are bigger
    • the smallest bacteria are about the size of the largest viruses