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Viruses
- Major cause of infectious disease
- Cannot replicate on their own - non-living
- No genus species classification
- Can cause cancer
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Virus Characteristics
- Small, aceullar
- Obligate intracellular parasites
- DNA or RNA genome
- Limited host range/specificity
- Hard to treat clinically
- Depend on our organelles (ribosomes) to replicate- no metabolism
- Infect all living organisms
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Ways to classify viruses
- Type of nucleic acids (DNA or RNA)
- Shape, host range, +/- envelope
- Common English name
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Virus Structure
- Nucleic Acid (DNA or RNA, double or single stranded)
- Capsid: (Protein shell) determines shape, composed of capsomeres
- Envelope - Some viruses possess phospholipid (derived from host cell)
- Glycoprotein Spikes: Allow attachment and determine viral specificity
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Viron
- A virus particle
- Metabolically inert until entry into host cell, dependent on host resources
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Bacteriophage
- Viruses that infect bacteria
- Head: Contains genome
- Collar, tail, sheath, plate, pin
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Bacteriophage
- Lytic Cycle
- Absorption: Phage is absorbed onto cell wall
- Penetration: Phage DNA is injected -- bacterial DNA disrupted
- Biosynthesis: Viral components produced from disrupted DNA
- Maturation: Phage heads and pieces of viral DNA are synthesized -- parts assembled -- cell wall breaks open \
- Release: Bacterial cell lyses -- virus released
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How are bacteriophage identified in lab?
Phage plaques on 'lawns' of susceptible bacteria
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Types of human viruses
- Lytic: Acute disease (ebola)
- Latent: Usually cause chronic disease (Chicken pox, HIV, herpes)
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Lytic
- Acute Disease - influenza
- Virus invades host cell, produces new virus, and lyses so the new viruses can be relased
- Virus then moves onto another cell
- Replicate immediately
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Latent
- Cause chronic disease
- Virus intergrates host cell DNA
- Replication is delayed
- Lysis when the cell feels threatened
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Animal Virus Replication
- 1.Attachment/Abs using viral spike binding to host cell receptor (membrane protein)
- *Antibodies can neutralize (block attachment)
- 2. Entry/penetration into host cell by membrane fusion (enveloped) or endocytosis (non-enveloped)
- 3. Uncoating of nucleic acid via capsid digestion
- *Latent: Integrate as dsDNA into host genome, delay replication/lysis, cause chronic disease
- *Lysis: viruses replicate fast
- 4.Biosythesis: Rapid for lytic and delayed for latent viruses until induction
- 5. Virus assembly and maturation
- 6. Release (virons exit host cell), lysis (may not be immediate some bud from host cell during shedding)
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Advantages/Disadvantages of Lytic
- Advantages: Produce virons quickly
- Disadvantages: Easily detected by immune system
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Advantage/disadvantages of Latent
- Advantages:Not detected by immune system
- Disadvantages: Will not replicate it host cell dies
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How does HIV attach to host cell?
- Viral Glycoportein Spikes
- Membrane protein reception - viral glycoprotein
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How do non-enveloped viruses enter the host cell?
Endocytosis
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HIV transmission
Blood semen, vaginal fluid, breast milk
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HIV origin
From Chimps 1920-30s in Africa
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HIV Lifestyle
- Retrovirus: RNA genome, only in humans
- Attaches to CD4 receptor in T(helper) cells via gp120 viral spike, enter via membrane fusion, uncoating
- Latent virus: RNA genome reverse transcribed to dsDNA, integrates into genome as provirus
- Provirus transcribed into mRNAs and RNA viral genomes, mRNA translated into protein
- Translated pre-protein cleaved into mature forms by viral protease, virus assembles, buds from cell, eventually lyses T(helper) host cell
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Seroconversion
Appearance of anti-HIV antibodies (within 3 mos exposure)
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Clinical HIV Infection
- Seroconversion
- Strong initial immune response followed by long chronic phase (9-12 yrs)
- Viral RNA load followed clinically, predicts course of infection
- Low T(h) cell count leads to opportunistic infections, onset of full blown AIDS
- Death from opportunistic ifections
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Opportunistic infections
TB, pneumonia, cancer, neurodegeneration
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AIDS therapies
- Antiretrovirals target viral enzymes RT, protease, and membrane fusion
- 1. Reverse transcriptionase inhibitors
- 2. Protease inhibitors inhibit viral protein maturation
- 3. Fusase inhibits membrane fusion
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AZT
- Nucleoside analog, terminates reverse transcription of viral RNA to DNA
- Disadvantages: Anemia, virus resistance
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Protease inhibitors disadvantages
large doses, side effects
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HAART
Combination (cocktail) therapy effective
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Influenza Virus
- Recurring epidemics, millions died in 1918-19
- Spike proteins are hemagglutinin (H) and neuraminidase (N), main viral antigens
- New strain each time
- Strains identified by H and N combination
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Spike proteins change due to
- Antigenic Drift
- Antigenic Shift
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Antigenic drift
Point mutations cause minor antigenic (H and N) changes over time
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Antigenic shift
- Genetic reassortment between human virus and other animal virus
- Causes sudden major shift in viral surface protein/antigen(s), produce virus no human has ever seen before
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Antigens
viral proteins on surface
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Influenza virus structure
- Enveloped
- RNA genome
- Lipid bilayer from host cell
- N and H spikes
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Virus and Cancer
- Associated with latent viruses such as HPV
- Uncontrolled cell division
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Oncogene
- Cancer causing gene
- Growth out of control
- genetic disruption
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