obligate intracellular parasite small: 10-100 nm nucleic acid genome dna or rna single- or...

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Obligate intracellular parasite Small: 10-100 nm Nucleic acid genome DNA or RNA single- or double-stranded Protein capsid Lipid envelope for some animal viruses What is a virus? Enveloped RNA virus Naked DNA virus

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Page 1: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Obligate intracellular parasite Small: 10-100 nm Nucleic acid genome

DNA or RNA single- or double-stranded

Protein capsid Lipid envelope for some animal viruses

What is a virus?

Enveloped RNA virus

Naked DNA virus

Page 2: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

No metabolism outside a host cell Requires host nucleotides, amino acids, enzymes, energy

Genome directs host cell to make virus proteins Copies of genome + proteins assembled into new viruses

Viruses don’t divide, they replicate

+

Page 3: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Is a virus a cell?

size

membrane

metabolism

composition

genetic material

virusescells

Page 4: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Is a virus alive?

living non-living

Page 5: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

1. Attachment

2. Entry

3. Uncoating

4. Nucleic acid replication & protein synthesis

5. Assembly

6. Exit

Virus replication

Page 6: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Virus protein binds membrane receptor Determines host range

Attachment

HPV(naked)

influenza virus(enveloped)

virus “spike” protein

virus “spike”protein

host cellreceptor

host cellreceptor

Page 7: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Naked virus usually enters by endocytosis Enveloped virus usually enters by fusion

Entry

influenza virus(enveloped)

HPV(naked)

Page 8: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Genome released from capsid proteins For naked virus, must also escape vesicle

Uncoating

HPV(naked)

influenza virus(enveloped)

Page 9: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Genome replicated Viral proteins synthesized by host ribosomes

Replication

HPV(naked)

influenza virus(enveloped)

envelope proteinsinserted into membrane

Page 10: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Viral proteins self-assemble into capsid Viral proteins package genome

Assembly

HPV(naked)

influenza virus(enveloped)

Page 11: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Naked virus lyses cell Enveloped virus “buds” out, taking membrane as envelope

Exit

influenza virus(enveloped)

HPV(naked)

Page 12: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Useful drugs must be selectively toxic: Kill the disease-causing organism Leave host cells unharmed

Antibiotics exploit differences between proks and euks: Unique cell wall carbohydrates in bacteria Unique structures of bacterial ribosomes Prokaryotic RNA polymerase

Viruses replicate in our own cells, using our own machinery

Antiviral drugs

Page 13: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Acyclovir Herpes family: herpes, chicken pox, shingles, etc. Blocks viral DNA synthesis Reduces duration and severity of infection

Antiviral drugs

Page 14: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

“Relenza” and relatives Influenza virus Prevents new budding viruses from

detaching and spreading Reduces duration of flu by ~2 days

Antiviral drugs

Page 15: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

HAART “cocktail” HIV virus Blocks 2 key viral enzymes Extends life Improves quality of life

Antiviral drugs

Page 16: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Our best weapon against viruses so far

Vaccination

Page 17: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Inject safe form of viral proteins (antigens) Immune system produces antibodies and memory cells Fast response to actual virus prevents disease

Vaccination

“flu shot”(killed virus)

Y YY

Y

anti-fluantibodies

anti

body p

roduct

ion →

time →≈10 days 1-2 days

infection withactual flu virus

Y YY

Y

YYY

Y YY

Y

Page 18: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Smallpox killed 300,000,000 in the 20th century

Edward Jenner developed vaccination in 1796

Vaccination allowed eradication of the disease Last case in 1977

Smallpox vaccination

Page 19: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Polio should be the next disease to be eradicated

2010968 cases

Vaccination

1988350,000 cases

Page 20: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Vaccine development difficult for some diseases (e.g., HIV) Difficulty of universal distribution Side effects, real and imagined Public resistance to vaccination Sensational, irresponsible media coverage Not an economic priority for many drug companies Regulatory issues: >10 years to license a new vaccine

Vaccine issues

Page 21: Obligate intracellular parasite  Small: 10-100 nm  Nucleic acid genome  DNA or RNA  single- or double-stranded  Protein capsid  Lipid envelope

Mutation New influenza virus strains (need a shot every year) “Swine flu” or “Bird flu” becomes human flu pandemic?

Species jump HIV probably evolved from a chimpanzee virus SARS coronavirus may have started as a bat virus

Spread from isolated population Public attention/media

Emerging viral diseases