Download Viruses Outline Discovery of Viruses Nature of Viruses

Outline
Viruses
The Discovery of Viruses
The Nature & Structure of Viruses
Bacteriophages
Disease Viruses
Virus Reproduction
AIDS
Virus Therapies
Emerging Viruses
Viruses and cancer
Prions
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Discovery of Viruses
1892 Russian Dmitri Ivanovski
Could not filter disease agents causing
Tobacco mosaic disease.
1898 Dutch botanist, Martinus Biejerinck
“kills’ tobacco mosaic disease agent at 90C.
1935 - Wendell
Stanley isolated and
crystallized the
Tobacco Mosaic
Virus
Nature of Viruses
1. Agents of Disease
found in virtually all organisms
host range usually specific
2. No cell organization
3. No Metabolism
4. No organelles
5. Cannot reproduce independent of cells
6. Set of genetic instructions
7. Renegade nucleic acid coated with protein
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Virus Structure
Nature of Viruses
1. Nucleic Acid Core
All viruses have same basic structure
(1) Nucleic acid core – DNA or RNA
Double-stranded – most DNA viruses
Single-stranded – most RNA viruses
Bacteriophage
(2) Capsid – protein envelope around nucleic
acid core
2. Protein
Capsid
HIV
(3) Envelope – membrane-like
3. Envelope
(4) Specialized enzymes inside capsid
Phospholipid bilayer
Proteins
Glycoproteins
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SARS Virus Genome
SARS virus
Severe acute respiratory syndrome
1. RNA Virus
2. 29,751 nucleotides
3. Six encoding genes make
2 Replicases
Spike proteins
Envelope glycoproteins
Membrane glycoprotein
Nucleocapsid protein
Viruses come
in a variety of
shapes
Helical - Tobacco mosaic
Icosahedral – Adenovirus
Complex - Bacteriophage
Viral genome of E. coli bacteriophage
48,502 nucleotides
23 proteins Æ development & maturation
Other enzymes Æ integrate virus DNA into host genome
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Viral Genome Structure
Viruses vary in size, as well as in shape
1. DNA Viruses Æ have Double-Stranded DNA
Varicella zoster (Chicken pox)
Herpes simplex (Herpes)
Epstein-Barr (Mononucleosis)
2. RNA Viruses Æ have Single Stranded RNA
(+) Stranded RNA Æ RNA = mRNA
HIV (AIDS)
Enterovirus (Polio)
(-) Stranded RNA Æ RNA bases complimentary to mRNA
Influenza (flu)
Rhabdovirus (rabies)
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Virus Replication
1) Virions - viruses outside cells
metabolically inert
Virus Replication – Lytic Cycle
Entry
Adsorption
2) Viruses are obligate intracellular parasites
-Host range = Suitable cells for a virus
-Tissue tropism = Types of cells infected
Rabies virus Æ neurons
Hepatitis virus Æ liver cells
3) Virus hijacks cell transcription & translation
machinery
4) Viruses can remain dormant or latent for years
Chicken pox Æ children
Shingles Æ Adults
Synthesis
Release
Assembly
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Virus Replication – Lytic Cycle
Bacteriophage Replication – Lytic Cycle
Prophage
- Adsorption = Viral attachment
- Entry = Viral entry
- Synthesis = Viral components are made
- Assembly = Components are put together
- Release = Viral exit
Lysogenic
Cycle
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Bacteriophage Replication – Lysogenic Cycle
- Adsorption = Viral attachment
- Entry = Viral entry
Induction Æ Prophage exits
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genome and enters lytic cycle
Virus Replication – Two Cycles
-Lytic cycle = Virus kills the host cell
-Lysogenic cycle = Virus incorporates into
the cell’s genome
INTEGRATION
INDUCTION
Lytic phage are called virulent
- Synthesis = Viral components are made
- Assembly = Components are put together
- Release = Viral exit
Lysogenic phage are called temperate
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HIV and AIDS
• HIV = Human Immunodeficiency Virus
• AIDS = Acquired immune deficiency syndrome
Immune Response
4. B Cells produce
Antibodies
3. Cytotoxic
T Cell
1. Macrophage
5. Memory B Cells
2. Helper T Cell
Helper T Cells activated by Antigenpresenting Macrophages
Fig. 26.2c(TE Art)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
gp120 glycoprotein
Human immunodeficiency
virus (HIV)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
gp120
glycoprotein
HIV Infection
HIV
2.HIV enters cell
by endocytosis.
Envelope
1. HIV
Attachment to
CD4 & CCR5
Host cell DNA
Capsid
3. Reverse
Transcriptase
Makes DNA
4. Virus DNA integrates
Into DNA of host cell
Enzyme
RNA
6. Virus exits
macrophage
by exocytosis
5. Transcription of virus DNA
produces RNA to be translated.
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mutated
HIV
gp120
glycoprotein
Helper T Cell
CD4 receptor
CXCR4
Coreceptor
specific to T cells
HIV Infection
2.HIV enters cell
by endocytosis.
1. HIV
attachment
3. Reverse
Transcriptase
Makes DNA
Host Cell DNA
HIV Replication
4. Virus DNA
integrates
Into host cell DNA
6. Virus exits
by cell lysis
5. Transcription of virus DNA
produces RNA to be translated
or serve as viral genome.
HIV & Disease Evolution
HIV Therapies
1. Combination Therapy – Synthetic drugs
Block Virus Replication
Block Viral Protein Synthesis
2. Vaccine – Introduce defective gene (nef)
3. Blocking entry of virus into cell
Chemokines block entry
Mutated coreceptors (CCR5)
4. Blocking RNA replication
Naturally occuring Cell Antiviral
factor blocks virus replication
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Vaccine
Influenza
Viruses
Types of Flu Virus:
Different Capsid Protein
Type A, B & C…
Type A Æ serious epidemics in humans
Type B & C Æ mild human infections
Subtypes of Flu Virus = Strains
Different Envelope proteins (protein spikes)
Hemaglutinin “H”– gets virus in cell.
Neuraminidase “N”– gets virus out.
Emerging Viruses
Emerging Viruses
Deer mouse hantavirus
hemorrhagic-type infection
Highly fatal
Ebola virus
hemorragic virus
≈ 90% fatal
SARS virus:
respiratory infection
≈ 8% fatal
1. Stimulates production of antibodies.
2. Why a new flu vaccine every year?
Viral H and N genes are highly variable
1. mutation
2. recombination.
Example Type A flu virus:
13 “H” Subtypes
9 “N” Subtypes
Pandemic = global infections
1918 A(H1N1) killed 40 million people
1957 A(H2N2) killed 100,000 Americans
1968 A(H3N2) killed 70,000 Americans (infected 50 million)
Emerging Viruses
SARS
-Severe acute respiratory syndrome
-Caused by a coronavirus
-Host is civets
-RNA genome contains
six main genes
-SARS vaccines currently
being developed
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Viruses and Cancer
Prions
Viruses may contribute to about 15% of all
human cancers
Viruses can cause cancer by altering the
growth properties of human cells
-1. Triggering expression of oncogenes
-2. Disrupting tumor-suppressor genes
In June 2006, the FDA approved the use of a
new HPV vaccine to prevent cervical cancer
“Proteinaceous infectious particles”
Cause transmissible spongiform
encephalopathies (TSEs)
-Mad cow disease
-Scrapie in sheep
-Creutzfeldt-Jacob disease in humans
Animals have normal prion proteins (PrPc)
-Misfolded proteins (PrPsc) cause disease
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