jimtrue.com : school : BSC2011 : CH 18: Genetics of Viruses

Posted by Jim True on August 24, 2004 5:38 AM. Last Updated October 22, 2006 9:23 PM

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CH 18: Genetics of Viruses

Viral Characteristics

• Virus - any of a large group of infectious agents which are typically pathogenic.
• Pathogen -- Any agent that causes disease.
• Viruses include an enormous number of different structures which have a tremendous effect on living organisms.
• However, they are currently considered by most biologists to be non-living particles.
• There are several reasons for this non-living classification:
  1. They are acelluar (they do not possess cellular structure
  2. they cannot metabolize and do not exhibit growth or development.
  3. They do possess materials of heredity, but cannot reproduce except when on or in a living cell.
• The "life/non-life" status of viruses is still being debated, however, it is widely accepted that viruses have an evolutionary connection to living organisms. The biological imperative is reproduction in kind; all living species exist to reproduce themselves. If the focus of life is to reproduce in order to maintain a competitive edge with other lifeforms then a virus could be considered the "perfect lifeform" because it has no other function (and no additional material in it's makeup) EXCEPT for the perfect reproduction of itself.
• What viruses ARE -- extremely small particles (usually measured in nanometers or billionths of a meter) which consist of:
  • Nucleic Acid Core -- either DNA or RNA but not both.
    • In addition, the genome of viruses may be double stranded or single stranded DNA or RNA and how they control reproduction also varies (Table 18.1).
  • Capsid -- a protein coat of variable shape.
    • Capsid shapes are distinctive and include three main types:
      1. Helical -- having a spiral shape.
      2. Polyhedral -- possessing a faceted surface. the number of facets varies.
      3. Combination -- exhibits both a polyhedral "head" and a spiral "tail".
    • The capsid consists of capsomeres, specific protein subunits. Many capsids are repeating capsomeres of the same protein.
  • Many viruses will also possess a viral envelope made up of material that is mainly from the host cell membrane, but also incorporating viral molecules as well.
• Because they are considered non-living and also because of their extremely small size, there is no real taxonomic classification of viruses.
• Instead they are grouped according to:
  • Capsid shape
  • enclosed genetic material
  • what they infect
• Different types of viruses havea a very limited range of organism or even cell types that they can infect, a narrow host range
• Host -- an organism which serves as an energy source for a pathogen (or a parasite).
• Many viruses are species-specific, infecting only a single type of host, and in eukaryotes, may even be tissue specific, eg. HIV (leukocytes), polio virus (nervous tissue).
• The limitations are due to the fit between the proteins of the capsid or viral envelope and specific receptors on the surface of the host cell.

Viral Reproduction

• Viral reproduction ALWAYS occurs within the host cell(s) in the following general fashion:
  • Viral genome (DNA or RNA) enters the host cell.
  • Replication of the genome occurs through either DNA synthesis (DNA viruses) or a special process in RNA viruses.
  • Production of the capsids occurs through transcription and translation (DNA viruses) or direct translation (RNA) of the viral genome.
  • The host provides all the "raw materials" for construction. The virus takes over the metabolic process of the cell and forces it to do it's bidding, either by taking over the nucleic acid processes or through taking over protein production.

There are three main groups of viral hosts:

1. Bacterial Viruses

Viruses infecting bacteria are referred to as bacteriophages (or phages). Phage means "to eat".

• These have been the most intensively studied of the viruses.
• They posses the most complex of the capsids, usually combination type.
• DNA is the genetic material in phages.
• There are two infectious pathways exhibited by phages:
  1. Lytic -- this pathway results in the destruction of the bacterial host during the release of replicated viral particles.
     • Some phages, termed virulent phages, reproduce only in this fashion (virulent means incredibly pronounced; a virulent phages will definitely destroy the cell).
     • In a lytic infection, the virus first attaches to the bacterial cell.
     • Viral DNa is injected into the host cell.
     • The viral DNA "overrides" the bacterial DNA causing the bacterium to generate new viral DNA and capsids.
     • The new viral particles are assembled and exit the host by rupturing the cell membrane and wall, lysing the cell, hence the name of the pathway.
     • Bacteria can "fight back" against phages by mutations of their receptor sites, as well as by enzymes that attack and disassemble the viral genome.
     • It is also possible for certain types of phages, called temperate phages, to control viral reproduction without destruction of the host.
  2. Temperate (Lysogenic) -- This pathway does not cause the immediate destruction of bacterial hosts but can spread a viral infection even more widely.
     • Infection starts in the same way as for the lytic path, attachment and injection of viral DNA.
     • The DNA is then INCORPORATED into the bacterial DNA.
     • Once incorporation takes place, the bacteriophage is referred to as a prophage.
     • It is able to do this because a repressor gene in the viral genome prevents the lytic genes from being expressed.
     • Thus, every time the bacterium divides by binary fission, the prophage is duplicated, therefore, EVERY new bacterium is infected! Since some bacteria can replicate in as little as 15 minuts, the number of hosts can increase rapidly.
     • In some prophages additional genes besides the repressor gene may be expressed.
     • These may cause a change in the characteristics of the host bacterium.
     • There are many cases where uninfected harmless bacteria become toxic when infected by a prophage.
     • Examples include:
       • Clostridium botulinum -- Harmless when uninfected, but produces the toxins causing botulism when a prophage is present.
       • Corynebacterium diptheriae -- harmless when uninfected, causes diptheria when infected with a prophage.
       • Clostridium tetani -- when uninfected, a harmless inhabitant of soil, but with a prophage, can cause tetanus.
     • Temperate cells can turn lytic when exposed to certain environmental triggers, e.g., exposure to radiation.
     • This shift to the lytic pathway has the potential for both massive destruction of the bacterial hosts plus increased chances for infection of new cells.

2. Animal viruses

Animal viruses vary in shapes and attachment structures and may contain either DNa or RNA (see table 18.1, p.334)

• the attachment structures are proteins and their shape dictates what the virus will infect.
• In many cases, animal viruses possess a viral envelope.
• Most animal viruses are highly host and tissue specific.
• In those animal viruses with a viral envelope, the envelope is usually derived from the host cell membrane.
• In addition, there will be viral glycoproteins in the envelope that allow attachment to receptor sites on the surface of the host cell.
• Infection is by the fusion of the viral envelope with the host cell membrane, allowing the viral genome to enter.
• As with bacteriophages, the viral genome takes over the cell and cause new viral material to be produced.
• the new viruses typically exit the host by exocytosis, incorporating host cell membrane into their viral envelope.
• The infection spreads, usually without the destruction of the host cell.
• Some animal viruses such as herpesviruses incorporate themselves into the host cell genome, creating a provirus. [Genome is the totality of the genetic material].
• These viruses can remain resident for the life of the animal, only periodically causing infectious outbreaks.
• Few bacterial viruses possess RNA as the genome, but many animal viruses are RNA viruses (see Table 18.1, categories III, IV, V and VI).
• DNA viruses are replicated by DNA synthesis processes, but RNA viruses are duplicated differently.
• Single stranded RNA's exhibit several different ways of producing new viral material:
  1. The RNA can act as mRNA and cause translation of new viral RNA genome, e.g., polio and rubella viruses.
  2. The virus carries an enzyme within the capsid that serves as a polymerase, reading the RNA genome and producing new RNA that acts as mRNA, e.g., rabies, measles, influenza.
  3. The most complex synthesis path is found in the retroviruses ("retro" -- backward).
     • These posses a special enzyme, reverse transcriptase, which transcribes the RNA genome into a DNA strand that is integrated into the host chromosome.
     • This integrated DNA is then transcribed by the host RNA polymerase to produce mRNA, which is then translated into the new viral RNA, e.g. HIV.

Animal Infections

• The effects of the viruses on animals range from mild to lethal, and temporary to permanent.
• The effects depend on what the viral infection actually does, e.g., one type of herpes virus causes "cold sores", which are temporary because skin easily replaces itself, whereas polio destroys central nervous tissue, which cannot regenerate.
• Some symptoms of viral infection, such as fever, are part of the animals defense mechanisms to try to "burn up" the viral (or infectious bacteria) proteins.
• Vaccine ("Vacca" -- cow) -- Harmless variants of pathogenic microbes used to stimulate immune defenses. (One of the first vaccines created was developed from CowPox, thus the name).
• Once viral infections occur, they can NOT be treated by antibiotics ("anti" -- against; "bios" -- life). Chemical derivatives created and produced by living organisms to destroy pathogens; usually developed from bacterias, plants and fungi. Antibiotics work against living cells; not against viruses.

3. Plant Viruses

Most plant viruses contain RNA. Shape is variable although many are spiral.

• Typically transmitted plant to plant by sucking insects or injury (horizontal transmission), infected seeds or asexual transmission (vertical transmission).
• They are transmitted cell to cell via plasmodesmata.
• Viral RNA attaches directly to ribosomes of cells and are translated as new viral RNA.
• Plant viruses cause a variety of disorders including:
  • "Leaf blight", where regions to all of the leaf are withered (loss of food to the plant).
  • withering of flowers and/or fruit (loss of reproductive material).
  • Stunted growth (susceptibility to disease, may not reproduce).
  • In many cases, plant viruses may not immediately kill the plant, but if economically important, may prevent the plant from being used for harvest.
• Tobacco Mosaic Virus -- causes leaf blight, which is the part of the plant that is harvested.
• Citrus Canker -- because it stunts and ultimately kills citrus trees, infected trees must be destroyed immediately.

Other Infectious Particles

• There are actually two groups of recently discovered non-living infectious particles that are even smaller than viruses!
  1. Viroids -- Composed of a 250-400 circular nucleotide strand of RNa with no capsid.
     • Viroids use host enzymes to construct new RNA strands.
     • The pathogenic actions of viroids are still not clearly known, however, they seeem to mainly infect plant hosts.
  2. Prions (Pree - ons) -- Even more unusual, as these particles have NO nucleic acids!
     • they are a protein-like polypeptide chain of approximately 250 amino acids.
     • Lacking nucleic acids, it is uncertain how prions are formed and replicated.
     • The current hypothesis is that prions are incorrectly folded proteins that cause other proteins to change to an incorrect shape when they come into contact with them.
     • It is also uncertain how they causes disease, but they are clearly pathogenic.
     • all prions are animal pathogens associated with the nervous system and invariably fatal, e.g., "Mad Cow Disease" and Jakob-Kreuzfeldt syndrom. Proper name for Mad Cow is Bovine Spongiform Encephalophogy.

Evolution of Viruses

• How viruses originated is uncertain.
• The currently accepted hypothesis is that they arose as nucleic acid fragments that were somehow released from the cells of living organisms, since they possess either DNA or RNA as living cells do.
• Evidence to support this hypothesis is that viruses are host and even tissue specific.
• This is probably because their genetic structure only allows them to infect cells or organisms to which they are genetically similar and from which they are probably originated.
• Viruses are mobile genetic elements.
• There are two similar elements in bacterial and eukaryotic cells:
  1. Plasmids, circular DNA molecules in bacteria and eukaryotic yeasts (Kingdom Fungi).
     • These can replicate independently of the cells genome and also move from cell to cell.
  2. Transposons -- Segments of DNA that can move from one location to another within the cellular genome.
     • will discuss with respect to bacterial biology.

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