Download Chapter 18 Lecture Notes: Viruses of Eukaryotes

Chapter 18 Lecture Notes: Viruses of Eukaryotes
I.
Differences between eukaryotes and prokaryotes and the consequences to viral reproduction
A. Eukaryotes (esp. animal cells) do not have cell wall
1. virus attached to receptors in the plasma membrane; different receptors are located
on different cells which results in distinct clinical manifestations
2. penetration of the virus– a variety of ways including
a) nucleic acid is "injected" though the plamsa membrane
b) fusion of enveloped virus envelope with the plamsa membrane and release
of virus nucleocapsid into the cytoplasm à uncoating of virus nucleic acid in
the cytoplasm
c) virus enters via receptor medicated endocytosis à fusion of endosome with
lysosome
(1) either enveloped virus can also fuse with lysosomal membrane
thereby releasing nucleocapsid into the cytoplasm à uncoating of virus
in cytoplasm
(2) or uncoating of virus in acidic lysosome à nucleocapsid enters
cytoplasm via viral protein induced transport through the lysosomal
membrane
3. Release of phage – a variety of ways including
a) cell lysis (naked viruses)
b) budding from any cell membrane (enveloped viruses)
c) intracellular spread (actin tails propel virus from one cell into another via
membrane fusion)
B. Compartmentalization of DNA replication via host DNA polymerase and transcription via
host RNA polymerase in the nucleus
1. Some transcription must occur in the nucleus unless the virus carries a viral RNA
polymerase in its capsid
a) herpes virus use host RNAP in the nucleus
b) pox viruses use viral RNAP that was brought into the cell in the
nucleocapsid
2. DNA replication must occur in the nucleus unless the virus encodes a viral DNA
polymerase in its capsid
a) herpes virus replicates in the nucleus using viral DNAP that was transcribed
with host RNAP in the nucleus
b) pox viruses replicate in the cytoplasm using viral DNAP that was transcribed
via viral RNAP that was brought into the cell in the nucleocapsid
c) parvovirus requires host DNAP for replication
C. mRNAs must be processed for translation
1. + strand RNA viruses must have a "Cap-like structure" so that the host ribosome
will bind the mRNA a
2. RNA viruses mRNAs need polyA tail so that they are stable and can be exported
from the nucleus for translation in the cytoplasm
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II.
RNA viruses (4 groups based on modes of replication and transcription)
A. "Transcription" of RNA viruses:
1. For positive ss RNA viruses, the viral genome IS the template for translation
2. For negative ss RNA viruses, the RNA is converted to mRNA by viral RNAdependent RNA polymerase (transcriptase) that is carried with in the virus; animal cells
do not have this enzyme
3. For dsRNA viruses, the RNA is converted to mRNA by viral RNA-dependent RNA
polymerase (transcriptase) that is carried with in the virus
4. For retroviruses (also + RNA)
a) +RNAà +RNA/-DNA via RNA-dependent DNA polymerase activity of
reverse transcriptase (RT) that is carried in the nucleocapsid à
b) +RNA/-DNA à –DNA via ribonuclease H activity of RT à
c) –DNA à + DNA (provirus) via DNA-dependent DNA polymerase activity
of RT à
d) provirus serves as template for transcription in the nucleus with host RNAP
B. Replication of viral genomes:
**Note that replicase core enzyme is the same as transcriptase; various modifications
(phosphorylations, additions of extra protein subunits) alter the functions between replicase and
transcriptase. Frequently the mRNA sequence does not equal progeny RNA sequence
1. positive ss RNA viruses
viral replicase makes + RNA (replicative form) that is used as a template to
make + RNA for the nucleocapsid
2. negative ss RNA viruses
viral replicase makes + RNA (replicative form) that is used as a template to
make more - RNA for the nucleocapsid
3. ds RNA
mRNAs complex with viral proteins and are all copied into one long RNA
strand to form a dsRNA for packaging in the nucleocapsid
4. retroviruses – provirus serves as the template for +RNA synthesis (see above in
transcription)
III.
Types of infections
A. Acute – rapid onset, short duration, frequently lytic (influenza)
B. Persistent/chronic – virus is produced by cell over a long period of time; may or may not be
symptoms (Hepatitis B)
C. Latent – virus is present but not replicating; no symptoms (herpes simplex I)
D. Slow virus – virus causes an infection in which symptoms are extremely slow to develop
E. Transformation – infection of virus leads to uncontrolled growth of the cell (cancer) – see
below
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IV.
Effect of viral infection on the host cell
A. Cell death due to
1. Inhibition of host DNA, RNA, or protein synthesis
2. Damage to cell lysosomes
3. Alteration of plasma membrane
4. Toxic effect of viral proteins
5. Formation of inclusions bodies that disrupt cell structure
6. Disruption of the chromosome by viruses that integrate
B. Cell transformation
1. Cancers linked to viruses (correlation of virus and cancer, evidence includes viruses
within tumor cells, animal models)
a) Burkitt's lymphoma (B cell cancer) and nasopharyngeal cancer/Epstein-Barr
virus
b) Liver cancer/ Hepatitis B
c) Cervical cancer/HPV
d) Some adult T cell leukemias/HTLV
2. Ways that viruses can promote cancer
a) Bring oncogenes into the cell – many disrupt the cell growth control system
b) Integrate into the chromosome such that viral promoter now turns on an
unexpressed cellular oncogene
c) Integrate into the chromosome such that a cell growth regulatory gene is
inactivated
d) Depress the immune systems' ability to detect and destroy transformed cells
V.
Non-animal viruses
A. Plant viruses – things to consider
1. Usually RNA viruses – unlike animal cells, most plants contain RNA-dependent
RNA polymerase
2. Since plants have complex cell walls, infection of the plant typically occurs
a) through damaged tissue
b) through infected pollen or ovules
c) through insect carriers, nematodes, fungus,
B. Fungal and algae viruses – less characterized than animal viruses
C. Insect viruses
VI.
Viroids and Prions
A. Viroids
1. circular, single-stranded RNAs of 350-370 nucleotides that "appears" rod-like due
to extensive intrastrand basepairing
2. does not code for a protein
3. no capsid
4. replicated by host DNA polymerase that mistakes them for DNA
5. transmitted via mechanical means or via pollen or ovules
6. cause a variety of crop diseases by unknown mechanism
7. may have arose from introns (non-coding RNA that is spliced out of eukaryotic
mRNAs
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B. Prions
1. proteinaceous infectious particle
2. 33-35 kDa hydrophobic membrane protein PrP
3. protein is present in the brains of normal animals
4. abnormal PrP alters normal PrP molecules in the brain so that they become
abnormal too
5. causes slow, degenerative neurological diseases
a) mad cow disease
b) kuru
c) Creutzfeldt-Jakob disease
6. alternative hypotheses are that there is a nucleic acid associated component
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