(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