Smallpox
Tobacco mosaic virus infection
Polio
Potyvirus infection
Bacteriophage
Mumps
Herpes simplex type 2
infection
VIRUSES CAUSE DISEASE
What is a virus?
-Obligate intracellular parasite
-Small: 10-100 nm
-Structure
-Nucleic acid genome
-Protein capsid
-Lipid envelope for some animal viruses
“spike”
capsid
Enveloped viruses
Nonenveloped viruses
Virus replication: Problem
What is needed for virus replication:
Protein synthesis
DNA replication
PROBLEM:
Small genome
Virus replication: Solution
- Virus infects a host cell in order to replicate
-no metabolism outside the host cell
-requires host nucleotides, amino acids, enzymes, energy
- Viral genome directs host cell to make viral proteins
- Copies of genome + proteins assembled into new viruses
What is a virus?
Viruses are noncellular, nonliving
infectious particles consisting of a
genome surrounded by a protein
coat.
Is a virus a cell?
cells
viruses
genetic material
dsDNA
DNA or RNA, ds or ss
composition
nucleic acids (DNA and RNA)
1000s of proteins
carbohydrates
lipids
nucleic acid (DNA or RNA)
capsid proteins (1-10s)
lipid envelope (some animal viruses)
metabolism
enzymes
break down sugars for energy
synthesize DNA, proteins, etc.
no active enzymes
no energy generation
no synthesis of molecules
membrane
always present
essential for transport
no functional membrane
no transport
size
1-10 μm for prokaryotes
10-100 μm for eukaryotes
10-100 nm (similar to ribosome size)
A virus does not qualify as a cell.
What is a virus?
Viruses are noncellular, nonliving
infectious particles consisting of a
genome surrounded by a protein
coat.
Is a virus alive?
living
non-living
• Some characteristics of living things
• Most consider viruses non-living
What is a virus?
Viruses are noncellular, nonliving
infectious particles consisting of a
genome surrounded by a protein
coat.
What organisms and host cells do
viruses infect?
Virus replication
1. Attachment
2. Entry
3. Uncoating
4. Nucleic acid replication & protein
synthesis
5. Assembly
6. Exit
Attachment
-Virus protein binds membrane receptor
-Determines host range
host cell
receptor
virus “spike” protein
Adenovirus
(naked)
host cell
receptor
virus “spike”
protein
Influenza virus
(enveloped)
Entry
-Naked virus usually
enters by endocytosis/ followed by endosomal
membrane lysis
-Enveloped virus usually enters by fusion with the plasma
membrane or the endosomal membrane
Adenovirus
(naked)
Influenza virus
(enveloped)
Uncoating
-Genome released from capsid proteins
Adenovirus
(naked)
Influenza virus
(enveloped)
Replication
-Genome replicated
-Viral proteins synthesized by host ribosomes
envelope proteins
inserted into membrane
Adenovirus
(naked)
influenza virus
(enveloped)
Assembly
-Viral
proteins self-assemble into capsid
-Viral proteins package genome
Adenovirus
(naked)
Influenza virus
(enveloped)
Exit
-Naked virus lyses cell
-Enveloped virus “buds” out, taking membrane as envelope
Adenovirus
(naked)
influenza virus
(enveloped)
Viruses are very diverse
Tobacco mosaic virus
(plant virus):
naked
ssRNA genome
helical capsid
Bacteriophage T4
(bacterial virus):
naked
dsDNA genome
complex capsid
Poliovirus
(replicating in cell):
naked
ssRNA genome
icosahedral capsid
Influenza virus:
enveloped
ssRNA genome
helical capsid
How are viruses classified?
• Enveloped vs Nonenveloped
• Genetic material
– DNA (single stranded or double
stranded)
– RNA (single stranded or double
stranded)
Helical:
Marburg
virus
Icosahedral:
Adenovirus
• Capsid structure
– Helical (rod shape)
– Icosahedral
– Complex
Complex:
Bacteriophage
How is viral infection treated?
– For a bacterial infection, a
doctor can prescribe
antibiotics which kill the
bacteria.
– For a viral infection: rest,
fluids, aspirin, etc.
Why are there so few
options for treating a
viral illness?
Antiviral drugs
• 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
Targets for antiviral drugs
Nonenveloped virus
Enveloped virus
Targets for antiviral drugs
Acyclovir
-Herpes family: herpes, chicken pox, shingles, etc.
-Blocks viral DNA synthesis
-Reduces duration and severity of infection
Targets for antiviral drugs
Relenza
-Influenza virus
-Prevents new budding viruses from detaching and spreading
-Reduces duration of flu by ~2 days
Antiviral drugs
• HAART “cocktail”
–
–
–
–
HIV virus
Blocks 2 key viral enzymes
Extends life
Improves quality of life
There are no drugs today
that can cure any viral disease.
Vaccination
• Our best weapon
against viruses so far
Vaccination
• Inject safe form of viral proteins (antigens)
• Immune system produces antibodies and memory cells
• Fast response to actual virus prevents disease
Smallpox vaccination
• 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
Vaccination
• Polio should be the next disease to be eradicated
1988
350,000 cases
2009
1,595 cases
Vaccine issues
• 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
Where do “new” viruses come
from?
Emerging viral diseases
• Mutation
– New influenza virus strains (need a shot every year)
– “Swine flu” or “Bird flu” becomes human flu pandemic?
influenza hemagglutinin
Emerging viral diseases
• Species jump
– HIV probably evolved from a chimpanzee virus
– SARS coronavirus may have started as a bat virus
SARS coronavirus
Emerging viral diseases
• Spread from isolated population
• Public attention/media
VIRUSES USED TO TREAT DISEASE
GENETIC DISEASE
Ex: Hemophilia A/B, Duchenne muscular dystrophy, cystic fibrosis
Problem:
Failure to produce a certain protein
Solution:
Viral vectors used to deliver the gene encoding the missing
protein