Challenges to an obligate intracellular parasite
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Transcript of Challenges to an obligate intracellular parasite
Challenges to an obligate intracellular Challenges to an obligate intracellular parasiteparasite
• 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 Virus-cell interactions may vary with type of cell infectedinfected
• 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 - 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
PERSISTENT, TEMPERATE: Replication PERSISTENT, TEMPERATE: Replication without cell deathwithout 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 INFECTIONSNONPRODUCTIVE INFECTIONS LYSOGENY, LATENCY 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 Attachment: Specificity beginsbegins here hereVirus attachment site and cell receptorVirus 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)
What is the value of knowing the receptor What is the value of knowing the receptor for a virus?for a virus?
Receptor sitesReceptor 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 sitesReceptor sites
• 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 co-receptors
• Unrelated viruses may use the same receptor
– Adenovirus (fiber knob) vs coxsackie (groove)
– HIV and GBV - C(HepG)
How do we determine the receptor?How do we determine the receptor?
• 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