Transcript Challenges to an obligate intracellular parasite

Challenges to an obligate intracellular
parasite
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Gain entry to host cell
Survive host defenses
Do not destroy cell while you need it
Compete for host resources to multiply
Exit and survive passage to new host cell
Virus-cell interactions may vary with type of cell
infected
• Productive - progeny produced
– Cytopathogenic: results in cell death
– Persistent: cell survives
– Transforming: cell survives and changes properties
• Non productive - no progeny produced
– Latent: can revert to productive
– Transforming: cell changes properties
– Abortive: Lacking needed factors
– Null: No receptors
PRODUCTIVE INFECTIONS CYTOPATHOGENIC, CYTOCIDAL, VIRULENT,
LYTIC
• Vegetative virus replicates
and cell dies
– virus product kills cell
- nuclease
– virus takes over host
machinery - access to
ribosomes
– virus kills cell during
lysis/release
– virus induces
apoptosis programmed cell death
• Useful for assay/count
of viruses - plaques,
CPE
Cucumber mosaic
virus
PERSISTENT, TEMPERATE: Replication
without cell death
• Release typically by budding - fewer per unit time but
longer time period
• Mechanisms leading to persistence
– Makes little demand on host resources
– Inhibits apoptosis
– Progeny reduced due to interferon (IF) or antibody so
rate of cell replication matches destruction
– Production of defective interfering particles (DI) deletion mutants that compete with and dilute
concentration of parent helper virus
NONPRODUCTIVE INFECTIONS
LYSOGENY, LATENCY
• Virus nucleic acid maintained
• If host cell reproduces so does virus nucleic acid
• May be integrated as prophage or provirus or may be
cytoplasmic episome
• May give host new characteristics due to some gene
expression (Lysogenic conversion; transforming viruses)
• Viral product may prevent apoptosis in certain cells
• Ability to return to vegetative state for many in same or
different cell (different disease - VZV)
• Presence shown by PCR or probes
• Transformation
– May or may not produce progeny depending on type of virus
– Virus product/presence turns on expressions of oncogenes
• Abortive infections: Permissive versus nonpermissive cells
– Infection but no functional progeny
• Missing factors for replication
• Failure to process proteins
• Null infections
– Lack receptors
– May be permissive if transfection or other means to infect
Attachment: Specificity begins here
Virus attachment site and cell receptor
• envelope glycoproteins
• capsid proteins
• ends of filaments of bacterial
rods (all filamentous animal
viruses are enveloped)
• penton proteins (poliovirus canyon formation)
• penton fibers (12 per virion)
• A proteins (single copies)
• Tailed phages - tail fiber tips (6
on Teven); tail pins (reversible
vs irreversible)
• May be multiple sites or
one
• Attachment sites are
highly conserved
• Adjacent ab binding sites
may not be
– Polio vaccine blocks
near attachment site
• Virus can escape detection
but remain infectious
(HIV)
Plant viruses bypass this step
Aphid on bean leaf
transmitting virus
What is the value of knowing the receptor
for a virus?
Receptor sites
• Essential to host cell function (Achilles pore)
• Present in multiple copies
• Narrow vs broad host range (universality of receptor)
– HIV vs rabies
• Tissue tropism
Receptor sites
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LPS - T4,T3
OmpF porin - T2
TonA iron transport - T1,T5
Nucloside transport - T6
Maltose transport - Lambda
Flagellum, pilus, teichoic acid,
capsule, membrane
• Receptors and coreceptors
• Unrelated viruses may use
the same receptor
– Adenovirus (fiber
knob) vs coxsackie
(groove)
– HIV and GBV C(HepG)
How do we determine the receptor?
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Susceptible cells
Removal and loss of binding
Examine resistant mutants
Inhibition assays
– Monoclonal antibodies
directed against cells
surface
– compete with soluble
receptors
• Transform resistant cells to
sensitive cells with receptor
DNA