Polio

Smallpox

MumpsPotyvirus infection

Tobacco mosaic virus infection

Bacteriophage VIRUSES CAUSE DISEASE

Herpes simplex type 2 infection

What is a virus?-Obligate intracellular parasite-Small: 10-100 nm-Structure

-Nucleic acid genome-Protein capsid-Lipid envelope for some animal viruses

Enveloped viruses

“spike”

capsid

Nonenveloped viruses

Virus replication: Problem

What is needed for virus replication:Protein synthesisDNA 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?

1-10 μm for prokaryotes10-100 μm for eukaryotessize

always presentessential for transportmembrane

enzymesbreak down sugars for energysynthesize DNA, proteins, etc.

metabolism

nucleic acids (DNA and RNA)1000s of proteinscarbohydrateslipids

composition

dsDNAgenetic material

virusescells

10-100 nm (similar to ribosome size)

no functional membraneno transport

no active enzymesno energy generationno synthesis of molecules

nucleic acid (DNA or RNA)capsid proteins (1-10s)lipid envelope (some animal viruses)

DNA or RNA, ds or ss

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.

• Some characteristics of living things• Most consider viruses non-living

Is a virus alive?living 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?

1. Attachment2. Entry3. Uncoating4. Nucleic acid replication & protein

synthesis5. Assembly6. Exit

Virus replication

Attachment

Adenovirus(naked) Influenza virus

(enveloped)

virus “spike” protein

virus “spike”proteinhost cell

receptorhost cellreceptor

-Virus protein binds membrane receptor-Determines host range

Entry

Influenza virus(enveloped)

Adenovirus(naked)

-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

Uncoating

Adenovirus(naked) Influenza virus

(enveloped)

-Genome released from capsid proteins

Replication

Adenovirus(naked) influenza virus

(enveloped)

envelope proteinsinserted into membrane

-Genome replicated-Viral proteins synthesized by host ribosomes

Assembly

Adenovirus(naked) Influenza virus

(enveloped)

-Viral proteins self-assemble into capsid-Viral proteins package genome

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

Exit

influenza virus(enveloped)

Adenovirus(naked)

Viruses are very diverse

Bacteriophage T4

(bacterial virus):naked

dsDNA genomecomplex capsid

Tobacco mosaic virus(plant virus):nakedssRNA genomehelical capsid

Influenza virus:enveloped

ssRNA genomehelical capsid

Poliovirus(replicating in cell):nakedssRNA genomeicosahedral capsid

How are viruses classified?

• Enveloped vs Nonenveloped• Genetic material

– DNA (single stranded or double stranded)

– RNA (single stranded or double stranded)

• Capsid structure– Helical (rod shape)– Icosahedral– Complex

Helical: Marburg virus

Icosahedral: Adenovirus

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?

• 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

Targets for antiviral drugs

Nonenveloped virus

Enveloped virus

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

Targets for antiviral drugs

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

Antiviral drugs

There are no drugs todaythat can cure any viral disease.

• 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

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

Smallpox vaccination

20091,595 cases

• Polio should be the next disease to be eradicated

Vaccination

1988350,000 cases

• 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

Where do “new” viruses come from?

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

Emerging viral diseases

influenza hemagglutinin

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

Emerging viral diseases

SARS coronavirus

• Spread from isolated population• Public attention/media

Emerging viral diseases

VIRUSES USED TO TREAT DISEASE

Problem:Failure to produce a certain protein

Solution:Viral vectors used to deliver the gene encoding the missing protein

GENETIC DISEASEEx: Hemophilia A/B, Duchenne muscular dystrophy, cystic fibrosis