Chapter 13 (Part I):Chapter 13 (Part I):

Characterizing Viruses, Viroids, Characterizing Viruses, Viroids, and Prionsand Prions

Introduction to VirusesIntroduction to Viruses ““VirusVirus”” originates from Latin word originates from Latin word ““poisonpoison””..

Term was originally used by Pasteur to describe Term was originally used by Pasteur to describe

infectious agent for rabies.infectious agent for rabies.

First virus discovered was tobacco mosaic disease virus First virus discovered was tobacco mosaic disease virus

(TMV) in 1890s.(TMV) in 1890s.

Distinguished from bacteria by being Distinguished from bacteria by being ““filterable agentsfilterable agents””

in early 1900s.in early 1900s.

In 1930s: TMV was isolated and purified. Electron In 1930s: TMV was isolated and purified. Electron

microscope was used to observe viruses.microscope was used to observe viruses.

By 1950s science of virology was well established.By 1950s science of virology was well established.

First Virus Discovered: Tobacco Mosaic Virus

This plant virus was first discovered in the 1890s Leaf on the left is infected, leaf on the right is not

``Characteristics of all viruses``Characteristics of all viruses No cells: Acellular infectious agents (no No cells: Acellular infectious agents (no

organelles, cell membrane, etc.)organelles, cell membrane, etc.) Obligate intracellular parasitesObligate intracellular parasites Possess either DNA or RNA, never bothPossess either DNA or RNA, never both Replication is directed by viral nucleic acid Replication is directed by viral nucleic acid

within a cellwithin a cell Do not divide by binary fission or mitosisDo not divide by binary fission or mitosis Do not grow or respond to environmentDo not grow or respond to environment No metabolism: Lack genes and enzymes No metabolism: Lack genes and enzymes

necessary for energy productionnecessary for energy production Depend on host cell ribosomes, enzymes, and Depend on host cell ribosomes, enzymes, and

nutrients for protein productionnutrients for protein production Smaller than most cellsSmaller than most cells

Viruses are Smaller Than Most Cells

Components of mature viruses (virions):Components of mature viruses (virions):

Virion:Virion: Virus outside of a cell (extracellular state) Virus outside of a cell (extracellular state) CapsidCapsid: Protein coat made up of many protein : Protein coat made up of many protein

subunits (capsomeres). Capsomere proteins subunits (capsomeres). Capsomere proteins may be identical or different.may be identical or different.

Genetic MaterialGenetic Material:: Either RNA or DNA, not both Either RNA or DNA, not both

Nucleocapsid = Capsid + Genetic MaterialNucleocapsid = Capsid + Genetic Material

Additionally Additionally somesome viruses have an: viruses have an: EnvelopeEnvelope: Consists of proteins, glycoproteins, : Consists of proteins, glycoproteins,

and host lipids. Derived from host membranes.and host lipids. Derived from host membranes.

Found in Found in envelopedenveloped viruses. viruses.

NakedNaked viruses lack envelopes. viruses lack envelopes.

Viruses Have Either DNA or RNA Inside a Protein Capsid (Nucleocapsid)

Naked Virus Enveloped Virus

Viruses are classified by the following Viruses are classified by the following characteristics:characteristics:

Type of genetic materialType of genetic material Type of cells infected Type of cells infected

Host Host Target cellTarget cell

Capsid shape and sizeCapsid shape and size Number of capsomeresNumber of capsomeres Presence or absence of envelopePresence or absence of envelope Type of disease producedType of disease produced Immunological propertiesImmunological properties

Types of viral genetic material:Types of viral genetic material:Genetic material may be single stranded or double stranded:Genetic material may be single stranded or double stranded:

Single stranded DNA (ssDNA): Single stranded DNA (ssDNA): ParvovirusesParvoviruses

Double stranded DNA (dsDNA):Double stranded DNA (dsDNA): HerpesvirusesHerpesviruses AdenovirusesAdenoviruses PoxvirusesPoxviruses Hepadnaviruses* (Partially double stranded)Hepadnaviruses* (Partially double stranded)

Single stranded RNA (ssRNA): Single stranded RNA (ssRNA): May be plus (+) or minus May be plus (+) or minus (-) sense. Plus is equivalent to mRNA:(-) sense. Plus is equivalent to mRNA: Influenza viruses (-)Influenza viruses (-) Picornaviruses (+)Picornaviruses (+) Retroviruses (+) Retroviruses (+) Rhabdoviruses (-)Rhabdoviruses (-)

Double stranded RNA (dsRNA): Double stranded RNA (dsRNA): ReovirusesReoviruses

Capsid morphologyCapsid morphology: : Three basic shapesThree basic shapes

1.1. HelicalHelical: Ribbon-like protein forms a spiral around : Ribbon-like protein forms a spiral around the nucleic acid. May be rigid or flexible.the nucleic acid. May be rigid or flexible.• Tobacco mosaic virusTobacco mosaic virus

• Ebola virusEbola virus

2.2. PolyhedralPolyhedral: Many-sides. Most common shape is : Many-sides. Most common shape is icosahedronicosahedron, with 20 triangular faces and 12 corners., with 20 triangular faces and 12 corners.• PoliovirusPoliovirus

• HerpesvirusHerpesvirus

3.3. Complex virusesComplex viruses: Unusual shapes: Unusual shapes• Bacteriophages have tail fibers, sheath, and a plate attached Bacteriophages have tail fibers, sheath, and a plate attached

to capsid.to capsid.

• Poxviruses have several coats around the nucleic acid.Poxviruses have several coats around the nucleic acid.

Examples of Capsid Morphology

Host Range: Host Range: Spectrum of hosts a virus can infect.Spectrum of hosts a virus can infect. Bacteria: Called bacteriophages or phagesBacteria: Called bacteriophages or phages Animals: Wide range of virusesAnimals: Wide range of viruses Plants: Introduced by abrasions or parasitesPlants: Introduced by abrasions or parasites Fungi: No extracellular state knownFungi: No extracellular state known ProtistsProtists

Viral Specificity: Viral Specificity: Types of cells that virus can Types of cells that virus can infect. infect. • DermotropicDermotropic• NeurotropicNeurotropic• PneumotropicPneumotropic• LymphotropicLymphotropic• Viscerotropic: Liver, heart, spleen, etc.Viscerotropic: Liver, heart, spleen, etc.

Life Cycle of Animal VirusesLife Cycle of Animal Viruses1. 1. Attachment or adsorptionAttachment or adsorption: Virus binds to specific : Virus binds to specific

receptors (proteins or glycoproteins) on the cell receptors (proteins or glycoproteins) on the cell surface.surface.

2. 2. Entry (Penetration)Entry (Penetration):Virus enters cell through one :Virus enters cell through one of the following processes:of the following processes:

• DirectDirect penetration:penetration: Naked virion injects cell with Naked virion injects cell with its genome (poliovirus)its genome (poliovirus)

• MembraneMembrane fusion:fusion: Enveloped virus fuses with cell Enveloped virus fuses with cell membrane. Capsid enters the cell (measles, mumps)membrane. Capsid enters the cell (measles, mumps)

• Endocytosis: Endocytosis: Naked or enveloped virus stimulates Naked or enveloped virus stimulates the cell to take in virus through endocytosis the cell to take in virus through endocytosis (adenovirus, herpesviruses)(adenovirus, herpesviruses)

Direct Penetration of a Naked Animal Virus

Penetration by Membrane Fusion and Endocytosis

Life Cycle of Animal VirusesLife Cycle of Animal VirusesUncoating:Uncoating: Must occur for viruses that enter the Must occur for viruses that enter the

cell with their capsids intact. Separation of viral cell with their capsids intact. Separation of viral nucleic acid from protein capsid. nucleic acid from protein capsid.

Process is poorly understood. Process is poorly understood.

Lysosomal, cytoplasmic, or viral enzymes may be Lysosomal, cytoplasmic, or viral enzymes may be involved.involved.

Attachment, Penetration (Endocytosis), and Uncoating of Herpes Virus

Life Cycle of a DNA Virus

Life Cycle -Animal Viruses (Continued)Life Cycle -Animal Viruses (Continued)4. 4. Synthetic Phase:Synthetic Phase: Involves several processes:Involves several processes:

Synthesis of viral proteins in cytoplasmSynthesis of viral proteins in cytoplasm Replication of viral genome:Replication of viral genome:

• DNA viruses typically replicate in nucleusDNA viruses typically replicate in nucleus

• RNA viruses replicate in cytoplasmRNA viruses replicate in cytoplasm

Assembly of progeny virus particlesAssembly of progeny virus particles

The synthetic stage can be divided in two periodsThe synthetic stage can be divided in two periods:: Early periodEarly period: Synthesis of proteins required for : Synthesis of proteins required for

replication of viral genetic material.replication of viral genetic material. Late periodLate period: Nucleic acid replication and synthesis : Nucleic acid replication and synthesis

of capsid and envelope proteinsof capsid and envelope proteins

Life Cycle-Animal Viruses (Continued)Life Cycle-Animal Viruses (Continued)5. 5. Release of progeny virionsRelease of progeny virions: There are two : There are two

main mechanisms of release:main mechanisms of release:A. Lysis of cells:A. Lysis of cells: Naked viruses and pox viruses leave Naked viruses and pox viruses leave

cell by rupturing the cell membrane. cell by rupturing the cell membrane.

Usually results in death of the host cell.Usually results in death of the host cell.

Example: PoliovirusExample: Poliovirus

B. BuddingB. Budding: Enveloped viruses incorporate viral : Enveloped viruses incorporate viral proteins in specific areas of a membrane and bud proteins in specific areas of a membrane and bud through the membrane. through the membrane.

Envelope contains host lipids and carbohydrates.Envelope contains host lipids and carbohydrates.

Host cell does not necessarily die. Host cell does not necessarily die.

Example: Human Immunodeficiency VirusExample: Human Immunodeficiency Virus

Release of Enveloped Virus by Budding

Life Cycle of BacteriophagesLife Cycle of BacteriophagesT-Even Bacteriophages: Lytic CycleT-Even Bacteriophages: Lytic Cycle

Lytic: Lytic: Cell bursts at end of cycleCell bursts at end of cycle

1. 1. Attachment or adsorptionAttachment or adsorption: : Virus tail binds to Virus tail binds to specific receptors on the cell surface.specific receptors on the cell surface.

2. 2. Entry (Penetration)Entry (Penetration): Virus injects genetic : Virus injects genetic material (DNA) into cell. Tail releases lysozyme, material (DNA) into cell. Tail releases lysozyme, capsid remains outside.capsid remains outside.

3. 3. SynthesisSynthesis-Destruction of Bacterial -Destruction of Bacterial Chromosome: Chromosome: Bacterium stops making its own Bacterium stops making its own moleculesmolecules

Lytic Cycle of Bacteriophage

4. 4. Viral SynthesisViral Synthesis: : Viral proteins and nucleic Viral proteins and nucleic acids are made by infected cell acids are made by infected cell

Eclipse phaseEclipse phase: No virions can be recovered from : No virions can be recovered from infected cells at this point.infected cells at this point.

5. 5. AssemblyAssembly: Bacteriophage capsids and DNA : Bacteriophage capsids and DNA are assembled into complete virions.are assembled into complete virions.

6. 6. ReleaseRelease: : Bacteriophage virions are released Bacteriophage virions are released from the cell. Plasma membrane breaks open from the cell. Plasma membrane breaks open and cell lyses.and cell lyses.• Burst timeBurst time: Time from attachment to release of : Time from attachment to release of

new virions (20-40 minutes).new virions (20-40 minutes).• Burst sizeBurst size:: Number of new phage particles that Number of new phage particles that

emerge from a single cell (50-200).emerge from a single cell (50-200).

Lytic Cycle of Bacteriophage

Life Cycle of BacteriophagesLife Cycle of BacteriophagesBacteriophage Lambda: Lysogenic CycleBacteriophage Lambda: Lysogenic Cycle

1. 1. Attachment and PenetrationAttachment and Penetration: Virus tail binds : Virus tail binds to specific receptors on the cell surface and to specific receptors on the cell surface and injects genetic material (DNA) into cell.injects genetic material (DNA) into cell.

2. 2. CircularizationCircularization: Phage DNA circularizes and : Phage DNA circularizes and enters either lytic or lysogenic cycle.enters either lytic or lysogenic cycle.

Lysogenic CycleLysogenic Cycle

3. 3. IntegrationIntegration: Phage DNA integrates with : Phage DNA integrates with bacterial chromosome and becomes a bacterial chromosome and becomes a prophageprophage. Bacterial chromosome is not . Bacterial chromosome is not destroyed. Prophage remains destroyed. Prophage remains latentlatent..

Life Cycle of BacteriophagesLife Cycle of BacteriophagesBacteriophage Lambda: Lysogenic CycleBacteriophage Lambda: Lysogenic Cycle

4. Replication of Bacterial Cell: 4. Replication of Bacterial Cell: Each time the Each time the cell divides it makes a copy of the prophage.cell divides it makes a copy of the prophage.

5. 5. InductionInduction: Prophage DNA is removed from : Prophage DNA is removed from bacterial chromosome due to a stimulus (e.g.: bacterial chromosome due to a stimulus (e.g.: chemicals, UV radiation) and initiates a lytic chemicals, UV radiation) and initiates a lytic cycle. cycle.

6.6. Synthesis, Assembly and Release: Synthesis, Assembly and Release: Cell Cell becomes full of virions and breaks open.becomes full of virions and breaks open.

Lysogenic versus Lytic Cycles of Bacteriophage

Important Human VirusesImportant Human VirusesDNA Virus FamiliesDNA Virus Families1. 1. AdenovirusesAdenoviruses:: Cause respiratory infections, Cause respiratory infections,

such as the common cold. First isolated from such as the common cold. First isolated from adenoids.adenoids.

2. 2. PoxvirusesPoxviruses:: Produce skin lesions. Produce skin lesions. Pox is a pus filled vesicle. Pox is a pus filled vesicle. Cause the following diseases:Cause the following diseases:

SmallpoxSmallpox CowpoxCowpox Molluscum contagiasum.Molluscum contagiasum.

Smallpox: Poxviruses Cause Pus Filled Vesicles

Disease was eradicated worldwide by immunization in 1977.Source: Microbiology Perspectives, 1999.

Important Human VirusesImportant Human VirusesDNA Virus FamiliesDNA Virus Families3. 3. HerpesvirusesHerpesviruses: : Herpetic means to cause Herpetic means to cause

spreading cold sores. Over 100 species. spreading cold sores. Over 100 species. Eight infect humans:Eight infect humans:

Herpes simplex 1 (oral herpes)Herpes simplex 1 (oral herpes) Herpes simplex 2 (genital herpes)Herpes simplex 2 (genital herpes) Varicella-zoster virus (chickenpox and Varicella-zoster virus (chickenpox and

shingles)shingles) Epstein-Barr virusEpstein-Barr virus KaposiKaposi’’s sarcoma viruss sarcoma virus

Important Human Viruses (Continued)Important Human Viruses (Continued)

DNA Virus FamiliesDNA Virus Families4. 4. PapovavirusesPapovaviruses:: Cause warts (papillomas), Cause warts (papillomas),

tumors (polyomas), and cytoplasmic vacuoles tumors (polyomas), and cytoplasmic vacuoles Human papilloma virus is sexually Human papilloma virus is sexually transmitted and causes most cases of cervical transmitted and causes most cases of cervical cancer in women. Cervical cancers typically cancer in women. Cervical cancers typically take over 20 to 30 years to develop, most take over 20 to 30 years to develop, most women develop them in their 40s and 50s or women develop them in their 40s and 50s or older. Pap smears are used to detect them.older. Pap smears are used to detect them.

5. 5. HepadnavirusesHepadnaviruses:: Cause hepatitis and liver Cause hepatitis and liver cancer. Hepatitis B virus.cancer. Hepatitis B virus.

Biological Properties of HepadnavirusesBiological Properties of Hepadnaviruses Enveloped virus. Envelope contains middle, Enveloped virus. Envelope contains middle,

large, and major surface proteins.large, and major surface proteins. Many incomplete viral particles found in Many incomplete viral particles found in

infected individuals.infected individuals. Small circular DNA molecules that are partially Small circular DNA molecules that are partially

double stranded.double stranded. Long Strand: Constant length. 3200 nucleotidesLong Strand: Constant length. 3200 nucleotides Short strand: 1700 to 2800 nucleotides.Short strand: 1700 to 2800 nucleotides.

Genome encodes for a handful of proteins:Genome encodes for a handful of proteins: Surface antigens Surface antigens Capsid proteinsCapsid proteins PolymerasePolymerase Protein X: Stimulates gene expressionProtein X: Stimulates gene expression

RNA Virus FamiliesRNA Virus Families1. 1. PicornavirusesPicornaviruses: : Naked viruses with a single Naked viruses with a single

strand of RNA. Include the following:strand of RNA. Include the following: PoliovirusPoliovirus Hepatitis A virusHepatitis A virus Rhinoviruses: Over 100 viruses that cause the Rhinoviruses: Over 100 viruses that cause the

common cold.common cold.

2. 2. TogavirusesTogaviruses: : Enveloped ssRNA viruses. Enveloped ssRNA viruses. Cause rubella and horse encephalitis.Cause rubella and horse encephalitis.

3. 3. RhabdovirusesRhabdoviruses:: Bullet-shaped, enveloped Bullet-shaped, enveloped viruses. Cause rabies and many animal viruses. Cause rabies and many animal diseases.diseases.

Examples of RNA Viruses

Rubella Vesicular Stomatitis Virus

Mouse MammaryTumor Virus

Hydrophobia in rabies patient.Source: Diagnostic Pictures in Infectious Diseases, 1995

Rabies is Caused by a Rhabdovirus

Important Human Viruses (Continued)Important Human Viruses (Continued)

RNA Virus FamiliesRNA Virus Families4. 4. RetrovirusesRetroviruses:: Unique family of enveloped Unique family of enveloped

viruses. Have the ability to convert their viruses. Have the ability to convert their RNA genetic material into DNA through an RNA genetic material into DNA through an enzyme called enzyme called reverse transcriptasereverse transcriptase. .

Viral DNA is integrated into host Viral DNA is integrated into host chromosome (chromosome (provirusprovirus) where it can remain ) where it can remain dormant for a long time.dormant for a long time.

Include HIV-1 and HIV-2 which cause AIDS Include HIV-1 and HIV-2 which cause AIDS and Human T Lymphocyte viruses which and Human T Lymphocyte viruses which cause cancer. cause cancer.

Retroviruses Convert RNA into DNA via Reverse Transcriptase

Viruses and CancerViruses and Cancer

Oncogenic viruses: Oncogenic viruses: Approximately 20% of all Approximately 20% of all

human cancers are caused by viruses.human cancers are caused by viruses.

Oncogenes: Oncogenes: Viral genes that cause cancer in Viral genes that cause cancer in

infected cells.infected cells.

Provirus: Provirus: Viral genetic material integrates into Viral genetic material integrates into

host cell DNA and replicates with cell host cell DNA and replicates with cell

chromosome. Some viruses may incorporate host chromosome. Some viruses may incorporate host

genes which can cause cancer under certain genes which can cause cancer under certain

conditions.conditions.

Example: RetrovirusesExample: Retroviruses

DNA Oncogenic Viruses:DNA Oncogenic Viruses:

Adenoviridae (Rodents)Adenoviridae (Rodents) Herpesviridae (Epstein-Barr Virus and Herpesviridae (Epstein-Barr Virus and

KaposiKaposi’’s Sarcoma Herpes s Sarcoma Herpes Virus)Virus)

Papovaviridae (Papillomaviruses)Papovaviridae (Papillomaviruses) Hepadnaviridae (Hepatitis B)Hepadnaviridae (Hepatitis B)

RNA Oncogenic Viruses:RNA Oncogenic Viruses: Retroviridae (Human T-cell leukemia 1 & 2)Retroviridae (Human T-cell leukemia 1 & 2)