Exam 3: Viruses, prions_18.pdf

General Virus Characteristics

• Obligatory intracellular parasites

-Require living host cells to multiply

• Nucleic acid (DNA or RNA)

-ss OR ds

• Capsid

• Envelope

• No ribosomes

• No ATP-generating mechanism

•Range from 20 nanometer to 1000nanometer in length

Viral Structure, Terminology

• Virion-complete, fully developed viral particle

• Nucleic acid

• Capsid (capsomeres- subunits)

• Envelope

• Spikes

General Viral Morphology

• Helical

• Polyhedral (icosahedral)

• Enveloped viruses

• Complex viruses

Key Terms

• Host range: what host cells (species) a virus can infect

-Usually only 1 type of cell in a species

-Determined by specific host attachment sites and cellular factors

• Tropism: range of cells/tissues virus can infect

General Virus Life Cycle: 5steps

1. Attachment

2. Entry

3. Synthesis

4. Assembly

5. Release

1. Attachment

• Interaction between molecule on virion surface (ligand) and on host cell (receptor)

• Why have viral tropism

• Example: phage to LPS incell wall

2. Entry

• Genome or entire nucleocapsid enters cytoplasm

• Penetration/uncoating may occur at same time

1. Fusion of envelope with host PM

2. Endocytic pathway

3. Synthesis

•Virus factories

-May occur in host cytoplasm (viroplasms)

-May rearrange host cell membrane (replication complexes): protects from host cell immune system

• Strong regulation

-Early, middle, late genes

4. Assembly

• Form independent subassembly lines

• Lines eventually converge

• Packasome and terminase to move DNA into prohead

5. Release

• Lysis of host cell

• May release by budding (enveloped)

• Note: some move directly from 1 host cell to another by cell division, mating

Viral infection: lytic cycle

Viral infection: lysogenic

• Lysogeny: phage remains latent

• Phage DNA incorporates into host cell DNA

-Prophage: genetic material phage inserted into bacterial chromosome

-When the host cell replicates its chromosome, it also replicates prophage DNA

-phage conversion-the host cell exhibits new properties

Viral infection: animal cells

• Cytocidal: cell death

• Persistent infections

• Cytopathic effects: observable changes

•Cell rounding

•Cell detachment

• Inclusion bodies

• Alter cell metabolism

• transformation

Latent Viral Infections

• Latent virus : in asymptomatic host cell for long periods

• May reactivate due to changes in immunity

- Cold sores, shingles

Persistent Viral Infections

• A persistent viral infection occurs gradually over a long period; is generally fatal

- Subacute sclerosing panencephalitis (measles virus)

Viruses and Cancer

• Multiple cancers caused by viruses

- May develop long after a viral infection

- Cancer is not contagious

• Oncogenes transform normal cells into cancerous cells

• Oncogenic viruses become integrated into the host cell's DNA and induce tumors

Baltimore Classification: based on viral genome

dsDNA Viruses

• DNA viruses replicate their DNA in the nucleus of the host using viral enzymes

• Synthesize capsid in the cytoplasm using host cell enzymes

• Bacteriophages, archael viruses, insect viruses, vertebrates (herpesvirus, poxvirus)

•Varicella-zoster (chickenpox)

ssDNA Viruses

• Use dsDNA intermediate in life cycle

• Uses host cell enzymes

• Positive strand OR negative strand

• Examples: Pseudomonas virus Pf1, parvoviruses

dsRNA Viruses

• Must produce RNA-dep RNA polymerase (RdRp)

-Acts as replicase, transcriptase

• Example: rotaviruses (stomach flu, gastroenteritis)

ssRNA positive strand Viruses

• Translated upon entry

• Genomes act as mRNA

• Must make RdRp

• Examples: coronaviruses, Zika, hepatitis A

•Microcephaly from Zika virus infection early in pregnancy

ssRNA negative strand Viruses

• Must bring RdRp

• Viral RNA is transcribed to a + strand to serve as mRNA for protein synthesis

• Examples: Rabies, Ebola, Measles, mumps, influenza

• measles in children

Retroviruses

• Positive strand, uses Reverse transcriptase

-RNA-dep DNA polymerase

-DNA-dep DNA polymerase

-Ribonuclease

-Lacks proofreading

• Integrates into host cell's DNA

• Example: HIV

Reverse transcribing DNA viruses

• Reverse transcriptase to replicate genome

• Integrate into host genome

• Example: hepatitis B virus

Isolation, cultivation

• Viruses must be grown in living cells

• Bacteriophages are grown in bacteria

• Animal viruses: grown in embryonated eggs, cell/tissue culture

Antivirals

• Small molecules

• Inhibit virus-specific enzymes

• Target replication processes

• Limits duration of illness, severity

Prions

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Prions

• Proteinaceous infectious particles

• Inherited and transmissible by ingestion, transplant, and surgical instruments

• Difficult/impossible to eradicate/eliminate:

- Resistant to disinfectants - Autoclaves, medical sterilization no effect

- *cooking actually concentrates the prions

-Long latency

- Remain in environment

Prions Spongiform encephalopathies

- "Mad cow disease"

- Creutzfeldt-Jakob disease (CJD)

- Gerstmann-Sträussler-Scheinker syndrome

- Fatal familial insomnia

- Sheep scrapie

- Kuru

- Chronic wasting disease (CWD)

Prions Continued...

• Scrapie: sheep and goats

• PrPC: normal cellular prion protein, on the cell surface

• PrPSc: scrapie protein; accumulates in brain cells, forming plaques

Bovine spongiform encephalopathy

• "mad cow disease"

• Can be spread from diseased cattle to humans (Creutzfield-Jakob)

• Degeneration of nervous system

Kuru

Papa New Guinea (1950s)

• Fore tribe

• Out of love, respect would ingest every part of deceased family members (endocannibalism)

-Women/children ate the brain

-Return life force

• Tremors, loss of coordination

Chronic wasting disease...now in GA!

• "zombie deer disease"

• cervid family — elk, deer, reindeer, caribou, and moose

• Potential for spillover to humans...

• No plan if spillover occurs