Viruses: Nature and Properties

Filterable Virus

• Virus smaller than bacteria
• Found by passing infectious fluids through filters designed to trap bacteria
• Filtered fluid remained infectious

Size of Virus

• 15nm - 800nm

Viruses on the Biological Spectrum

• Infect every type of cell including bacteria, algae, fungi, protozoa, plants and animals

Early Discoveries

• Louis Pasteur developed a rabies vaccine
• Pasteur coined the term "virus" (Latin for poison)

Virion vs. Viroid

• Virion: A fully formed virus able to establish infection in a host. Consists of an infection agent and all plant pathogens
• Viroid: lacks a capsid and consists of a close circular RNA molecule

Properties of Viruses

• Infectious particles
• Active or inactive
• Obligate intracellular parasites: Cannot multiply unless they invade a specific host cell; must instruct the host cell's genetics and metabolic machinery to make and release new viruses

Viruses and Recognition

• Viruses follow a lock-and-key mechanism for entry in host cells.
• Some viruses have broader recognition abilities, infecting more than one type of cell.

Unique Properties of Viruses

• Are not cells. They are obligate intracellular parasites.
• Do not independently fulfill the characteristics of life.
• They are inactive macro-molecules outside their host.
• Cannot replicate biological function independently of a host organism.
• Can have either DNA or RNA, ranging from 20 to 450 nm
• May have a double-stranded DNA, a single-stranded DNA, a single-stranded RNA or a double-stranded RNA.
• Contain molecules on the surface that determine specificity for a host.
• Carry machinery to make essential proteins.
• Lack enzymes for most metabolic processes.

Viral Components

• Viruses are not cells
• Lack protein-synthesizing machinery
• Contain the parts needed to invade and control a host cell
  • External coating
  • Core containing nucleic acids

Capsid

• Shell that surrounds the nucleic acid (protein)
• Nucleocapsid: capsid and nucleic acid together

Envelope

• Usually a modified piece of the host cell membrane
• Matrix proteins: proteins that form a layer on the inside of the viral envelope. They play important roles in virus assembly, forming links or bridges between nucleocapsids/cores and the envelope

Complex Viruses

• Has different capsomeres
• The envelope will have phospholipids like all membranes

The Capsid

• Made of protein
• Naked viruses will only have a nucleocapsid
• Complex viruses will have a nucleocapsid covered by a membrane

Naked Viruses

• Consists only of a nucleocapsid
• Made of proteins with similar capsomeres

Spikes

• Found on both naked and enveloped viruses
• Project from either the nucleocapsid or envelope
• Allow viruses to dock with their host cells

Spike proteins

• Give the viruses its identity
• 20 spike proteins react to different cell receptors
• Tell the host cell which spike proteins to produce

The Viral Capsid

• The protective outer shell. It is made up of capsomeres, identical protein subunits, that spontaneously self-assemble to form the capsid
• Helical capsid: Rod-shaped capsomeres that form a continuous helix around the nucleic acid
• Icosahedral capsid: Three-dimensional, 20-sided figure with 12 evenly spaced corners

Viruses and Reproduction

• Viruses reproduce through an alive host cell
• The host cell provides the virus with ATP, chemicals, and allows the virus to produce its own protein (RNA or DNA)

Viral Production in a Cell

• The average cell produces ~50 million viruses
• Viral infections are typically short-term and can resolve in, if the body can handle it, 3-4 days

The Viral Capsid

• The viral capsid is a protein shell that encloses the viral genetic material
• Complex Capsids: Found in bacteriophages (viruses that infect bacteria). They have multiple protein types and take shapes that are not symmetrical.

The Viral Envelope

• Composed of the membrane system of the host cell (cell membrane or nuclear membrane)
• Regular membrane proteins are replaced with viral proteins
• Spikes: Protruding glycoproteins essential for attachment to the host cell
• Glycoproteins: Proteins with a glucosamine coating

Nucleic Acids

• Genome: the full complement of DNA and RNA carried by a cell
• Viruses contain either DNA or RNA, but not both
• The number of viral genes is small compared to that of a cell
• They possess only the genes necessary to invade host cells and redirect their activity. 31 viral genome: 4 or 5 genes; humans: 27,000; prokaryotic cells: 4,000-5,000
• The viral genome tells the host cell what it needs to produce.

Nucleic Acids - Positive-sense RNA

• Single-stranded RNA genomes ready for immediate translation into proteins.

Nucleic Acids - Negative-sense RNA

• RNA genomes that need to be converted into the proper form to be made into proteins.

Eukaryotic cells

• Do not have replicative RNA, so the virus would need to bring the enzyme itself.

Other Substances in the Virus Particle

• Enzymes for specific operations within the host cell:
  • Polymerases: synthesize DNA and RNA
  • Replicases: copy RNA
  • Reverse transcriptase: synthesizes DNA from RNA

X DNA virus replication

• Can only be replicated in the nucleus.
• The only time DNA is in the cytoplasm is during the cell cycle

Multiplication Cycles in Animal Viruses

• General phases in the life cycle of animal viruses:
  • Adsorption
  • Penetration
  • Uncoating
  • Synthesis
  • Assembly
  • Release from the host cell

Adsorption and Host Range

• Invasion begins when the virus encounters a susceptible host and adsorbs specifically to receptor sites on the cell membrane.
• Adsorb: to attach (similar to a virus)
• Absorb: to soak in (similar to a paper towel)

Host Range

• A virus can invade its host cell only through making an exact fit with a specific host molecule.
• Restricted host range: Hepatitis B only infects liver cells of humans.
• Intermediate host range: Poliovirus infects intestinal and nerve cells of primates.
• Broad host range: Rabies virus infects various cells of all mammals.

Virus Entry and Replication

• Penetration and Uncoating of Animal Viruses:
  • Endocytosis: The entire virus is engulfed by the cell and enclosed in a vacuole or vesicle.
  • Uncoating: Enzymes in the vacuole dissolve the envelope and capsid, releasing the virus into the cytoplasm.
  • Reverse transcriptase allows RNA to be made into DNA.

Entry of a Virus into Host Cell

• Viruses damage the host cell by taking parts of its membrane.

Replication and Protein Production

• Viral nucleic acid takes control over the host's synthetic and metabolic machinery
• Mechanism depends on whether the virus is DNA or RNA
• RNA viruses replicate in the cytoplasm
• DNA viruses replicate in the nucleus.

Synthesis of DNA Viruses

• The virus must be converted to DNA to replicate
• Proteins are formed by the cytoplasm and rRNA is made in the nucleus
• Viruses can be dormant in the host cell's cytoplasm, only in the DNA, where they insert their genome into the host cell's DNA. This can be due to nutrition, carcinogens, or stress.

Release of Mature Viruses

• Viral budding or exocytosis: Nucleocapsid binds to the membrane and viruses are shed gradually without destruction of the cell.

Damage to the Host Cell and Persistent Infections

Cytopathic Effects (CPEs)

• Virus-induced damage to the cell that alters its microscopic appearance
• Cells can become disoriented, undergo major changes in shape or size, or develop intracellular damage

Damage to the Host Cell (cont'd)

• Cytopathic effects (cont'd):
  • Inclusion bodies: Compacted masses of viruses or damaged cell organelles in the nucleus or cytoplasm
  • Syncytia (singular, syncytium): Fusion of multiple host cells into single large cells containing multiple nuclei

Persistent Infections

• A carrier relationship that develops in some cells
• The cell harbors the virus and is not immediately lysed

Provirus

• Viral DNA incorporated into the DNA of the host.
• Chronic latent state: periodic activation after a period of viral inactivity

Viruses and Cancer

• Oncogenic viruses: Experts estimate that up to 20% of human cancers are caused by viruses.
• Transformation:
  • Virus carries genes that directly cause cancer
  • Virus produces proteins that induce a loss of growth regulation in the cell
  • Will change identity in the cell

Viral Movement Between Cells

• In eukaryotic cells, a virus can move from one cell to another and move DNA between them, called transformation. This is called transduction in prokaryotic cells.

Oncogenes

• Produce the same protein, but increase the number causing the cell to divide rapidly.

Viruses that Infect Bacteria

• Bacteriophage (bacteria eater):
  • Discovered in 1915
  • Parasitize every known bacterial species
  • Often make the bacteria they infect more pathogenic for humans

Bacteriophage Life Cycle

• Bacteriophage (T-even):
  • "T-even" bacteriophage infect E.coli
  • T-2 and T-4
  • Most widely studied bacteriophage
  • Go through similar stages as animal viruses

Bacteriophage Life Cycle (Lytic Phase)

• Lytic phase or lytic cycle: life cycle of bacteriophage that ends in destruction of the bacterial cell.

Bacteriophage Life Cycle (Lysogenic Cycle)

• Lysogenic cycle: bacteriophage becomes incorporated into the host cell DNA.

The Danger of Lysogeny in Human Diseases

• Lysogenic conversion:
  • The acquisition of a new trait from a temperate phage
  • Responsible for the diphtheria toxin, cholera toxin, and botulism toxin

Using Cell Culture Techniques

• Detecting viral growth in culture:
  • Degeneration and lysis of infected cells.
  • Plaques:
  • Clear, well-defined patches in the cell sheet.
  • Develops when viruses released from an infected cell radiate out to surrounding cells.
  • Infection spreads gradually and symmetrically from the original point of infection

Satellite viruses

• Dependent on other viruses for replication
  • Adeno-associated virus (AAV)
    • Originally thought that it could only infect cells infected with the adenovirus.
    • Now found to infect cells infected with other viruses or had their DNA disrupted through other means.

Other Noncellular Infectious Agents

• Prion infection:
  • Exact mode of infection is unknown.
  • Protein composition.
  • Questions about how prions replicate given that they have no nucleic acid.

Other

• Missing proteins: Essentially are missing their proteins; depend upon cells that have already been infected.

Additional Information

• Do not have DNA or RNA, but are still able to replicate.
• All affect brain tissue.