Chapter 5 - Viruses and Prions

Obligate intracellular parasites

require living host cells to multiply

• have few to no enzymes for metabolism

• no ATP-generating mechanism

Definitive features of obligate intracellular parasites

• contain DNA or RNA (not both)

• contain a protein coat that protects the nucleic acid

• multiply inside living cells using host cell machinery

• produce structures to transfer viral nucleic acid to other cells

Host range

the spectrum of host cells a virus can infect

• can vary depending on the virus (very specific to broad)

• many viruses infect only specific types of cells in one species of host organism

• for example: bacteriophages are viruses that only infect bacteria

Virion

complete, fully developed viral particle, capable of causing infection

Virion Structure

• nucleic acid: DNA or RNA can be single- or double-stranded; linear or circular

• capsid: protein coat made of capsomeres (subunits)

• together these two structures compose the nucleocapsid

• spikes: projections on outer surface used for entry into the host cell

• some virions possess envelope: lipid, protein, and carbohydrate coating on some viruses (taken from the host membrane when virus exits)

Virus Multiplication - Animal Viruses

adsorption, penetration and uncoating, synthesis, assembly, release

Adsorption - Animal Viruses

virus attaches to receptors on host cell membrane

Penetration and Uncoating - Animal Viruses

• virus enters cell in a vacuole by membrane fusion (enveloped viruses) or receptor-mediated endocytosis (naked viruses)

• enzymes in vacuole dissolve membrane and capsid to release DNA

Synthesis - Animal Viruses

nucleic acid replication and protein production

• DNA viruses: DNA replication (nucleus), Protein synthesis (cytoplasm)

• RNA viruses: RNA replication and protein synthesis (cytoplasm)

Assembly - Animal Viruses

nucleic acid and capsid proteins come together to form nucleocapsid

Release - Animal Viruses

by budding (enveloped viruses) or rupture (naked viruses)

Budding

virus acquires portion of host cell membrane; cell may live

Rupture

nonenveloped viruses escape through holes in membrane, host cell typically

Pathogenic Properties of Viruses

evade host defenses by growing inside host cells

• immune cells cannot reach them

Cytopathic Effects of Viruses (CPE)

• visible effects of infection

• often cytocidal: result in cell death

• may be used to diagnose infection

• vary with virus (key difference is point in infection when they occur)

• stopping cell synthesis

• causing cell lysosomes to release enzymes

• creating inclusion bodies in the cell cytoplasm

• fusing cells to create a syncytium

CPE and Cancer - Pathogenic Properties of Viruses

• changing host cell function or inducing chromosomal changes (activating oncogenes)

• loss of contact inhibition in the cell, leading to cancer

Viruses and Cancer

• integration of oncogenic viruses can activate oncogenes

• normal cells transform into tumor cells

• acquire properties of cancer (altered growth from normal cells, cells may express tumor-specific antigens on the cell surface and in the nucleus)

Oncogenes

• involved in cell growth and proliferation or inhibition of apoptosis

• dozens have been identified

• activated oncogenes allow cells designated for apoptosis to survive and proliferate

Oncogenic viruses (oncoviruses)

can become integrated into the host cell’s DNA and induce tumors

often go undetected until cancer formation because

• most virions do not induce cancer

• cancers may develop long after initial infection

• cancers caused by viruses are not contagious

Latent infection

• periods with no infectious virus

• reactivation may occur due to changes in immunity

Chronic infection

• infectious virus present at all times

• occurs gradually over a long period

Virus Multiplication in Bacteriophage

• lytic cycle (lysis): phage causes lysis and death of the host cell

• lysogenic cycle (latency): phage DNA is incorporated into the host DNA

Lytic cycle

results in cell death by lysis (disintegration of cell by disruption of cell wall or membrane)

Stages of Lytic cycle

1. adsorption: phage attaches to host cell

2. penetration: phage penetrates host cell and injects its DNA

3. synthesis: phage DNA directs synthesis of viral components (DNA, proteins, etc.) by the host cell

4. assembly: viral components are assembled into virions

5. release: host cell lyses, and new virions are released

Lysogeny

phage remains latent (dormant or inactive)

• phage DNA incorporates into host cell DNA (called a prophage, when the host cell replicates, prophage is replicated)

• lysogenic phages can reproduce using both the lytic and lysogenic cycles

Outcomes of lysogeny

• immunity to infection by same phage

• specialized transduction (specific bacterial genes transferred to other bacteria by phage, changes genetic properties of bacteria)

Stages of lysogeny

1. prophage exits in galactose-using host (containing the gal gene)

2. phage genome excises carrying with it the adjacent gal gene from the host

3. page matures and cell lyses releasing phage carrying gal gene

4. phage infects a cell that cannot utilize galactose (lacking gal gene)

5. along with the prophage, the bacterial gal gene becomes integrated into the new host’s DNA

6. lysogenic cell can now metabolize galactose

Virus Growth

• viruses must be grown in living cells

• bacteriophages are grown in bacteria (phages form plaques)

Plaques

clearings on a lawn of bacteria on the surface of agar

• each plaque corresponds to a single virus; can be expressed as plaque-forming units (PFU)

Growing animal viruses - virus growth

• in living animals

• in embryonated eggs (virus injected into egg, growth signaled by changes or death of embryo)

• in cell cultures (tissues are treated with enzymes to separate cells, virally infected cells are detected via their deterioration, known as the cytopathic effect CPE)

Prions

• proteinaceous infectious particles

• cause of nine animal neurological diseases

• inherited and transmissible by ingestion, transplant, and surgical instruments

• cause of cell damage not yet known

• PrPC: normal cellular proin protein, on the cell surface

• PrPSc: scrapie protein; accumulates in brain cells, forming plaques

Spongiform encephalopathies

large vacuoles develop in the brain