Biol 202 Virology 3: cancer, prions, antiviral therapy

neoplasia

loss of cell cycle regulation leading to uncontrolled proliferation

anaplasia

cellular reversion to a less differentiated state

metastatis

spread of cancerous cells throughout body

oncogenes

cancer-causing genes

oncogene sources

mutated proto-oncogenes or from virus itself (oncovirus)

carcinogenesis

a complex multistep process, often involving oncogenes

oncovirus example

HPV16/18, with dsDNA, are associated with cervical and anogenital cancer

virus-associated cancer mechanisms

viral proteins bind tumour suppressing (regulatory) proteins in the host cell, oncovirus carries oncogene, altered cell regulation, promoter or enhancer insertion next to cellular oncogene

HPV protein examples

E6 promotes destruction of the host’s p53 which is responsible for triggering voluntary apoptosis. E7 binds to Rb which normally halts cell replication in case of faulty DNA

oncogene example

v-sis induces PD growth factor overexpression

promoter or enhancer insertion result

overexpression of a cellular protein

viroid

closed circular ssRNA pathogens with a few hundred nucleotides and no genes encoded. replication requires host DDRP. cause of many plant diseases

satellites (virusoids)

do not encode their own capsids, and parasitize a helper virus for genetic material and replication

virusoid genome

usually ssRNA, and do not encode their own RDRP

virusoid effects on helper virus

modulate up or down symptoms caused by helper host. alter (usually down) accumulation of helper viral DNA

virusoid example

chronic bee-paralysis satellite virus, parasitizes CBPV which causes hairlessness and susceptibility to bullying. CBPSV effect unknown

virusoids in hepatitis

hepatitus d (HDV), is helped by hepatitus B (HBV), and uses the HBV capsid

HDV acquisition

co-infection with HBV through blood/sexual contact, or super-infection of HBV-having individual

HDV effect

greatly exacerbates HBV infection

prion

proteinaceous infectious particle, an etiologic agent in neurodegenerative diseases

prion examples

scrapie (sheep), bovine spongiform encephalopathy, creutzfeldt-jakob disease (CJD) & variant vCJD, kuru (human)

prion protein forms

PrPC (normal) or PrPSc (abnormal)

prion agent effect

PrPSc interacts with normal PrPC, corrupting its conformation and causing generation of more PrPSc. PrPC molecules crosslink, stimulating neuronal apoptosis

antiviral drugs take advantage of

virus nucleic acid synthesis, virus-specific enzymes, life cycle processes such as entry and exit

influenza HA

haemagglutinin, used to bind to host

influenze internalization

endocytosis, endosome acidification. low pH prompts opening of M2 channel, which allows H+ into viral capsid.

H+ effect on influenza genome

disassociates matrix protein M1 from viral genome. this is needed to unpack the viral genome (ribonucleoprotein, RNP)

amantadine/rimantadine

prevent M2 from opening, so virion is not acidified. M1 stays stuck to RNP, genome is not unpacked

influenza exit

budding. envelope sticks to viral receptor containing sialic acid. neuraminidase digests the sialic acid, releasing virion

oseltamivir (tamiflu)/zanamivir

neuraminidase inhibitors. do not cure influenza, but shorten course of illness.

adenine arabinoside (vidarabine)

adenosine analogue, which competes for DNA polymerase active site, causing faulty DNA synthesis.

adenine arabinoside (vidarabine) use

treatment of herpes simplex virus (HSV 1&2), and Varicella roster virus (chicken pox, shingles)

acyclovir & varacyclovir

acyclovir is a guanosine analogue. valacyclovir is the oral prodrug form.

cidofovir

cytosine analogue

cidofovir use

broad anti-viral, used for herpesviruses, poxviruses, adenoviruses, papovavirus family

foscarnet

pyrophosphate analogue, blocks splitting of dNTP during DNA polymerization. dNTP hydrolysis provides energy for polymerization

HIV life cycle

attachment via 2 receptors, fusion, uncoating, reverse transcription, integration, transcription (RNA & mRNA), polyprotein translation (gene expression), budding & maturation

HAART cocktail

highly active anti-retroviral therapy. 3-4 drugs targeting various stages in HIV life cycle

RT inhibitors

nucleoside (NRTI) or non-nucleoside (NNRTI). inhibit reverse transcriptase

protease inhibitors (PI)

mimic peptide bond that is normally attacked by protease

integrase inhibitors

prevent HIV genome from integrating

fusion inhibitors

prevent HIV entry into cells. allow HIV to bind to CD4 but not fuse to membrane