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

• Useful for assay/count of viruses - plaques, CPE

Cucumber mosaic virus

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)

Plant viruses bypass this stepPlant viruses bypass this step

Aphid on bean leaf transmitting virus

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