Download Chapter 13—Viruses, Viroids, and Prions I. General Characteristics

Chapter 13—Viruses, Viroids, and Prions
I.
II.
General Characteristics of Viruses.
a. Are inert when not within a host cell.
b. Require a living host cell to multiply.
i. They are therefore considered to be obligate intracellular parasites.
c. Viruses contain DNA or RNA, but not both.
d. No ATP generating mechanism.
e. Viruses have a protein coat surrounding the nucleic acid.
i. Some viruses are also enclosed by an outer lipid envelope.
f. Little or no metabolic activity.
g. Viruses multiply inside living cells by using the host cell’s own enzymes, nucleic acids, amino
acids, ATP, etc.
i. Most drugs that would interfere with viral multiplication would have the same effect on
the host cell.
h. Host Range:
i. The range of host cells the virus can infect.
ii. The host range of a virus is determined by specific host attachment sites and cellular
factors necessary for viral multiplication.
1. Attachment sites include things such as cell walls, fimbriae, flagella, and plasma
membrane proteins.
iii. Most viruses infect only specific types of cells in one host species.
1. Bacterial viruses are called bacteriophages or phages.
i. Viral Size: Fig. 13.1.
i. Range from 20 to 1000 nm in length.
1. Remember, prokaryotes range in size from 1 µm to 10 µm, while eukaryotes
range in size from 10 µm to 500 µm.
Viral Structure.
a. Virion: A single mature, complete, infectious viral particle.
b. Nucleic Acid.
i. DNA or RNA is the primary genetic material in a given species of virus.
ii. Can be either a single strand nucleic acid or double strand nucleic acid:
1. Single strand DNA (ssDNA).
2. Double strand DNA (dsDNA).
3. Single strand RNA (ssRNA).
4. Double strand RNA (dsRNA).
iii. The nucleic acid can be linear or circular.
1. In some viruses, the nucleic acid is in several separate segments.
a. Influenzavirus.
b. Bird flu and genetic reassortment.
c. Capsid and Envelope. Fig. 13.2.
i. Capsid: Protein coat surrounding the nucleic acid of a virus.
1. Composed of subunits called capsomeres.
a. Proteins composing the capsomeres may all be the same, or they may be
composed of several different proteins.
ii. Envelope: Lipid layer external to the capsid. Fig. 13.3.
1. Also contains proteins and carbohydrates.
a. Some animal viruses become coated with the host cell’s plasma membrane
when released.
2. May or may not be covered with “spikes.”
a. Glycoproteins (antigens) that project from the surface of the envelope.
III.
IV.
V.
i. In some viruses, these glycoproteins serve as attachment points for
binding to host cells.
3. Viruses that have an envelope are said to be “enveloped viruses.”
iii. Nonenveloped Viruses:
1. Do not have an envelope.
iv. Infection with a virus stimulates the host to produce antibodies that will recognize and
bind to viral surface proteins (antigens).
1. Some viral proteins frequently mutate.
2. This allows different viral strains to infect you more than once.
a. I.e.: Influenzavirus.
d. General Morphology.
i. Viruses can be classified on the basis of their structure.
1. Helical Viruses. Fig. 13.4 a.
2. Polyhedral (many-sided) Viruses. Fig. 13.2 a.
3. Enveloped Viruses. Fig. 13.3 a.
4. Complex Viruses. Fig. 13.5 a.
a. Complicated structures.
b. Bacteriophages.
Taxonomy of Viruses.
a. Viruses are grouped into families based on:
i. Nucleic acid type.
ii. Replication strategy.
iii. Morphology.
b. Family names end in –viridae.
c. Genus names end in –virus.
d. Viral species: A group of viruses sharing the same genetic information and ecological niche (host
range). Common names are used in place of species names. There are no specific epithets.
e. Viral subspecies are designated by a number.
f. Example:
i. Family: Herpesviridae
ii. Genus: Simplexvirus.
iii. Common name: Human herpes virus (HHV).
iv. Subspecies: HHV 1, HHV 2, HHV 3.
Isolation, Cultivation, and Identification of Viruses.
a. Viruses must be grown in living cells.
i. Viruses that grow in plants and animals are difficult to maintain.
ii. Pathogenic viruses can only be grown in higher primates or humans.
b. Bacteriophages are relatively easily grown in bacterial cultures where they form plaques on a
lawn of bacteria.
c. Growing Bacteriophages in the Laboratory. [DO NOT DISCUSS]
d. Growing Animal Viruses in the Laboratory. [DO NOT DISCUSS]
e. Viral Identification. [DO NOT DISCUSS]
Viral Multiplication.
a. Ribosomes, tRNA, amino acids, ATP, and most enzymes needed for protein and nucleic acid
synthesis are supplied by the host cell and are used to synthesize viral proteins, enzymes, and
nucleic acids.
b. Multiplication of Bacteriophages.
i. Bacteriophages are DNA viruses that multiply by two alternative mechanisms: the lytic
cycle and the lysogenic cycle.
ii. Lytic Cycle. Fig. 13.10.
1. Attachment: Phage attaches by its tail fibers to the host cell.
a. The viral attachment site binds to a complimentary receptor site
(protein/antigen) on the bacterium.
2. Penetration: Phage lysozyme opens the cell wall, and its tail sheath contracts to
force the tail core and viral DNA into the cell.
3. Biosynthesis: Phage DNA circularizes and directs production of phage DNA and
proteins. Host DNA is destroyed (broken into fragments).
4. Maturation: Spontaneous assembly of phage components into virions.
5. Release: Phage lysozyme breaks cell wall to release new virions.
a. Host cell dies.
iii. One-Step Growth Experiment.
1. Burst Time: The time from attachment to release. Averages 20-40 minutes.
2. Burst Size: The number of virions released from a single cell. (Usually 50-200).
iv. Lysogenic Cycle. Fig. 13.12.
1. Lysogenic phages may proceed through a lytic cycle, but they can also insert their
DNA into the host cell’s DNA to begin a lysogenic cycle.
2. In lysogeny, the phage remains inactive, and the bacterial host cell is known as a
lysogenic cell.
a. Host cell remains alive during lysogeny.
3. Attachment and penetration can lead to the lytic cycle, or:
a. Following penetration, phage DNA can recombine with host DNA to form
a prophage. The cell then enters the lysogenic cycle.
i. Most prophage genes are repressed by repressor proteins.
ii. The lysogenic bacterium reproduces normally.
iii. Occasionally, the prophage may excise itself from the bacterial
chromosome to initiate the lytic cycle.
4. Consequences of lysogeny:
a. Lysogenic cells are immune to re-infection by the same phage.
b. Phage conversion can occur, where the host cell exhibits new properties.
c. Specialized transduction can occur. Fig. 13.13.
i. When a prophage is excised from the host chromosome, adjacent
genes from either side may remain attached to the phage DNA.
c. Multiplication of Animal Viruses.
i. Attachment: Virus attaches to proteins/glycoproteins of the plasma membrane.
1. Monoclonal antibodies can combine with viral attachment sites or the cell’s
receptor sites to prevent viral infection.
ii. Penetration:
1. Endocytosis encloses the virion within a vesicle.
a. If the virus is enveloped, the envelope is destroyed when lysosomes fuse
with the vesicle.
b. The capsid may also be digested (see uncoating below) or it may be
released into the cytoplasm of the host.
i. Lysosomes do not contain enzymes that break apart DNA or RNA.
2. Fusion is an alternate method by which enveloped viruses can enter the host cell.
a. The viral envelope fuses with the plasma membrane of the host, releasing
the capsid into the cell’s cytoplasm.
iii. Uncoating: Separation of the viral nucleic acid from the capsid via viral or host enzymes.
1. Poorly understood process that varies with the type of virus.
iv. Biosynthesis: Production of viral nucleic acid and proteins. Generally, the DNA is
copied in the nucleus.
v. Maturation: Nucleic acid and capsid proteins spontaneously assemble.
vi. Release:
1. Budding occurs with the release of enveloped viruses. Fig. 13.20.
a. The envelope is partially derived from the host plasma membrane or
nuclear membrane.
b. Does not necessarily kill the cell.
2. Nonenveloped viruses are released via the rupture of the host’s plasma membrane.
a. This kills the host cell.
d. Biosynthesis of DNA Animal Viruses. Fig. 13.15.
i. Attachment, penetration, and uncoating occur as discussed earlier.
ii. Viral DNA enters the host nucleus, and one of two things can happen:
1. Viral DNA can recombine with the host DNA to form a provirus.
a. The provirus remains permanently within the host DNA. (This is
different from a prophage, which can excise itself from the host
chromosome.)
b. The provirus may stay inactive within the host, but it will be replicated
whenever the host DNA replicates.
i. Mutagens can induce expression of a provirus that was previously
latent.
ii. The provirus can also convert the host cell into a tumor cell.
2. Alternatively, the viral DNA/provirus can be expressed, producing new virions.
a. “Early genes” of the virus are transcribed in the nucleus (using host RNA
polymerase) and translated in the cytoplasm (using host tRNA’s, amino
acids, and ribosomes) to produce proteins needed for viral DNA
replication in the nucleus.
b. Viral DNA replication then occurs using the host’s DNA polymerase
within the nucleus.
c. “Late genes” of the virus are transcribed in the nucleus (using host RNA
polymerase) and are translated in the cytoplasm (using host tRNA’s,
amino acids, and ribosomes) to produce capsid proteins and other
structural proteins.
d. Capsid proteins migrate into the nucleus where maturation occurs.
e. The virions are then transported along the endoplasmic reticulum to the
host cell’s membrane for release via budding or rupturing.
iii. New virions are then released.
iv. Adenoviridae. [DO NOT DISCUSS]
v. Poxviridae. [DO NOT DISCUSS]
vi. Herpesviridae. [DO NOT DISCUSS]
vii. Papovaviridae. [DO NOT DISCUSS]
viii. Hepadnaviridae. [DO NOT DISCUSS]
e. Biosynthesis of RNA Animal Viruses.
i. Nearly the same processes as seen in the DNA viruses, except for the ways in which viral
mRNA and viral RNA are produced.
ii. Biosynthesis of Positive-Strand RNA Animal Viruses. Fig. 13.17 (red arrows).
1. Attachment, penetration, and uncoating occur as discussed earlier.
2. Viral RNA is translated into two principal proteins:
a. One inhibits host cell synthesis of RNA and protein.
b. The other is RNA-dependent RNA polymerase, which catalyzes the
synthesis of another strand of viral RNA that is complementary to the base
sequence of the original positive viral RNA strand.
i. The new strand is an antisense (negative) strand, which serves as a
template to produce additional positive strands.
3. The positive RNA strands also serve as mRNAs for the translation of viral
proteins.
4. Once viral RNAs and viral proteins are synthesized, maturation and release occur.
VI.
a. Negative strand RNA molecules are broken down.
iii. Biosynthesis of Negative-Strand RNA Animal Viruses. Fig. 13.17 (purple arrows).
1. Attachment, penetration, and uncoating occur as discussed earlier.
2. Again, viral RNA translation leads to the synthesis of RNA-dependent RNA
polymerase, which catalyzes the synthesis of another strand of viral RNA that is
complementary to the base sequence of the original negative viral RNA strand.
a. The new strand is a positive strand, which serves as a template to produce
additional negative strands.
3. The positive RNA strands also serve as mRNAs for the translation of viral
proteins.
4. Once viral RNAs and viral proteins are synthesized, maturation and release occur.
a. The positive strand RNA molecules are broken down.
iv. Picornaviridae. [DO NOT DISCUSS]
v. Togaviridae. [DO NOT DISCUSS]
vi. Rhabdoviridae. [DO NOT DISCUSS]
vii. Reoviridae [DO NOT DISCUSS]
viii. Retroviridae. Fig. 13.19.
1. Multiplication of a Retrovirus in Animals.
a. Attachment, penetration, and uncoating occur as discussed earlier.
b. Members of this viral family contain two identical strands of + RNA and
the enzyme reverse transcriptase.
c. Technically, reverse transcriptase is an RNA-dependent DNA polymerase,
because it uses RNA as a template to make a new complimentary DNA
(cDNA) strand.
d. The newly synthesized cDNA strand is then used as a template for the
synthesis of another complimentary DNA strand, antiparallel to the
cDNA, yielding a double-stranded DNA molecule.
e. Reverse transcriptase also destroys the original viral RNA.
f. Viral DNA recombines with the host DNA to form a provirus.
i. The provirus remains permanently within the host DNA. (This is
different from a prophage, which can excise itself from the host
chromosome.)
g. The provirus may stay inactive within the host, but it will be replicated
whenever the host DNA replicates.
h. Alternatively, the provirus can be expressed, producing new virions.
i. Mutagens can induce expression of a provirus that was previously
latent.
ii. The provirus can also convert the host cell into a tumor cell.
i. In order to produce new virions, the viral DNA must be transcribed back
into mRNA that will direct viral protein synthesis and be incorporated into
new virions.
i. Viral mRNA is transcribed in the nucleus (using host RNA
polymerase) and transported into the cytoplasm.
ii. Translation occurs in the cytoplasm using host tRNA’s, amino
acids, and ribosomes to produce capsid proteins and other
structural proteins.
iii. Maturation occurs in the cytoplasm.
iv. New virions are then released by budding (for enveloped viruses)
or rupturing (for non-enveloped viruses).
Viruses and Cancer.
a. Several types of cancers are caused by viruses.
b. Cancer is the uncontrolled growth of cells.
VII.
VIII.
IX.
X.
i. Most cancers are thought to involve multiple mutations that accumulate sequentially.
1. Tissues are made of masses of cells.
2. A mutation that occurs in one of these cells can lead to a loss of control of the cell
cycle.
3. The mutant cell will reproduce faster than the normal cells, and mutant cells
accumulate.
4. Among the mutants, one cell may undergo another mutation in another gene,
causing even more loss of control of the cell cycle.
5. Double mutants accumulate even faster.
6. One of these cells experiences another mutation in a third control gene.
7. Loss of control of the cell cycle leads to faster mutant cell reproduction which
leads to increasing rounds of DNA replication and additional chances for more
mutations to occur.
c. The formation of a provirus represents a permanent genetic change in a cell. Therefore, viruses
that can form proviruses (DNA viruses and retroviruses) can cause cancer.
d. Oncogene: a gene that causes cancer (increases the rate of cellular reproduction) when it
experiences mutation.
i. Activated oncogenes transform normal cells into cancerous cells.
e. Tumor cells undergo transformation to acquire new properties.
i. Dedifferentiated (less specialized than normal cells).
ii. Increased growth rate.
iii. Loss of contact inhibition.
iv. Transplantable (can detach from one tissue and re-attach to another tissue = metastasis).
v. Invasive (will squeeze into tight spaces that normal body cells can’t exploit).
f. The genetic material of oncogenic viruses becomes integrated into the host cell's DNA.
g. DNA Oncogenic Viruses. [DO NOT DISCUSS]
h. RNA Oncogenic Viruses. [DO NOT DISCUSS]
Latent Viral Infections.
a. A virus remains in an asymptomatic host cell for a long period of time, and then suddenly
becomes active to cause disease.
b. The trigger for disease manifestation is usually a stressor (infection with another microbe, injury,
psychological stress, etc.).
c. Examples: Cold sores, shingles.
Persistent Viral Infections.
a. Disease progress occurs slowly over a long period of time, and is generally fatal.
b. Subacute sclerosing panencephalitis (measles virus) HIV.
Prions. Fig. 13.21.
a. Infectious proteins.
b. Inherited and transmissible by ingestion, surgical transplant, and contaminated surgical
instruments.
c. Spongiform encephalopathies: scrapie (sheep), Creutzfeldt-Jakob disease and variant
Creutzfeldt-Jakob disease (humans), Gerstmann-Sträussler-Scheinker syndrome (humans), fatal
familial insomnia (humans), kuru (humans), bovine spongiform encephalopathy (mad cow
disease). Chronic wasting disease (cervids = deer, elk, [moose?]).
d. PrPC, normal cellular prion protein, found on the surface of neurons.
e. PrPSc, scrapie protein, accumulate in brain cells forming plaques.
Plant Viruses and Viroids.
a. Plant viruses must enter through a wound in the plant or gain entry with the help of a plant
parasite (nematode, fungus, insect).
i. Infected plants can spread the virus to other plants via pollen and seeds.
b. Viroids are naked RNA molecules between 300-400 nucleotides long that fold back on
themselves.
i. The RNA does not code for proteins.
ii. Strictly plant pathogens.
iii. May have evolved from introns.