Chapter 1:Chapter 1:

VirusesViruses

Introduction to VirusesIntroduction to Viruses

“Virus” originates from Latin word “poison”. Term was originally used

by Pasteur to describe infectious agent for rabies. First virus discovered

was tobacco mosaic disease virus (TMV) in 1890s. In 1930s: TMV was

isolated and purified. Electron microscope was used to observe viruses.

Viruses - The Boundary of Life (www.dellpassovoy.com/www.dellpassovoy.com/VirusViruses.es.pptppt - - MiripMirip ) )

At the boundary of life, between the macromolecules (which are not alive)

and the prokaryotic cells (which are), lie the viruses and bacteriophages.

In isolation, viruses and bacteriophages show none of the expected signs

of life. They do not do any of the things we normally associate with life.

Strictly speaking, they should not be considered "living" organisms at all.

However, they are more complex than a lifeless collection of

macromolecules and they do show one of the most important signs of life:

the ability to reproduce at a fantastic rate but only in a host cell.

Characteristics of all virusesCharacteristics of all viruses

– Acellular infectious agentsAcellular infectious agents. . A virus is a non-cellular A virus is a non-cellular particle made up of genetic material and protein that particle made up of genetic material and protein that can invade living cells. can invade living cells. ((www.worldofteaching.com/powerpoints/biology/viruses.ppt - www.worldofteaching.com/powerpoints/biology/viruses.ppt - MiripMirip ) )

– Possess either DNA or RNA, never bothPossess either DNA or RNA, never both Replication is directed by viral nucleic acid within a cellReplication is directed by viral nucleic acid within a cell

– A virus is an obligate intracellular parasiteA virus is an obligate intracellular parasite containing containing genetic material surrounded by protein genetic material surrounded by protein (http://www.slideworld.org/viewslides.aspx/Introduction-to-Virology-ppt-67425)(http://www.slideworld.org/viewslides.aspx/Introduction-to-Virology-ppt-67425)

– Lack genes and enzymes necessary for energy Lack genes and enzymes necessary for energy productionproduction

– Depend on host cell ribosomes, enzymes, and nutrients Depend on host cell ribosomes, enzymes, and nutrients for protein productionfor protein production

– Incapable of independent metabolismsIncapable of independent metabolisms

Viruses are Smaller Than Most CellsViruses are Smaller Than Most Cells

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

CapsidCapsid:: Protein coat made up of many protein Protein coat made up of many protein subunits subunits

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

Genetic MaterialGenetic Material: Either RNA or DNA, not both: Either RNA or DNA, not bothNucleocapsid = Capsid + Genetic MaterialNucleocapsid = Capsid + Genetic Material

Additionally some viruses have an Additionally some viruses have an EnvelopeEnvelope (consists of proteins, (consists of proteins,

glycoproteins, and host lipids.Derived from host glycoproteins, and host lipids.Derived from host membranes.membranes.

Naked viruses lack envelopes.Naked viruses lack envelopes.

Viruses Have Either DNA or RNA Inside a Viruses Have Either DNA or RNA Inside a

Protein Capsid (Nucleocapsid)Protein Capsid (Nucleocapsid)

Influenza Virus Bacteriophage

Viruses are classified by the following Viruses are classified by the following

characteristics:characteristics:

– Type of genetic materialType of genetic material– Capsid shapeCapsid shape– Number of capsomeresNumber of capsomeres– Size of capsidSize of capsid– Presence or absence of envelopePresence or absence of envelope– Host infectedHost infected– Type of disease producedType of disease produced– Target cellTarget cell– 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):

Parvoviruses Parvoviruses – Double stranded DNA (dsDNA):Double stranded DNA (dsDNA):

HerpesvirusesHerpesviruses AdenovirusesAdenoviruses PoxvirusesPoxviruses Hepadnaviruses* (Partially double stranded)Hepadnaviruses* (Partially double stranded)

– Single stranded RNA (ssRNA): May be plus (+) or Single stranded RNA (ssRNA): May be plus (+) or minus (-) sense:minus (-) sense: Picornaviruses (+)Picornaviruses (+) Retroviruses (+) Retroviruses (+) Rhabdoviruses (-)Rhabdoviruses (-)

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

Capsid morphology:Capsid morphology:

PolyhedralPolyhedral:: Many-sides. Most common shape is Many-sides. Most common shape is icosahedron, with 20 triangular faces and 12 corners.icosahedron, with 20 triangular faces and 12 corners.

– PoliovirusPoliovirus– HerpesvirusHerpesvirus

Complex virusesComplex viruses: Unusual shapes: Unusual shapes HelicalHelical:: Ribbon-like protein forms a spiral around the Ribbon-like protein forms a spiral around the

nucleic acid. May be rigid or flexible.nucleic acid. May be rigid or flexible.– Tobacco mosaic virusTobacco mosaic virus– Ebola virusEbola virus– Bacteriophages have tail fibers, sheath, and a Bacteriophages have tail fibers, sheath, and a

plate attached to capsid.plate attached to capsid.– Poxviruses have several coats around the nucleic Poxviruses have several coats around the nucleic

acid.acid.

Active VirusActive Virus

1.1. ATTACHMENTATTACHMENT: A specific virus attaches to the : A specific virus attaches to the surface of a specific cellsurface of a specific cell

2.2. INVADEINVADE: The nucleic acid (DNA or RNA) of the : The nucleic acid (DNA or RNA) of the virus is injected into the cell. (Note : virus is injected into the cell. (Note : ~ ~ Penetration etc.)Penetration etc.)

3.3. COPYCOPY: The viral nucleic acid takes control of the : The viral nucleic acid takes control of the cell an begins to make new virus particles. cell an begins to make new virus particles. (Note : (Note : ~ Replication etc.)~ Replication etc.)

4.4. RELEASERELEASE: The cell bursts open, hundreds of new : The cell bursts open, hundreds of new virus particles are released from the cell. These virus particles are released from the cell. These virus particles go on to infect other cells. (Note : virus particles go on to infect other cells. (Note : ~ Lysis ---- although not always lysis/rupturing ~ Lysis ---- although not always lysis/rupturing host cell)host cell)

Life Cycle of Animal VirusesLife Cycle of Animal Viruses

1.1. 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.

1.1. PenetrationPenetration:: Virus enters cell through one of the Virus enters cell through one of the following processes:following processes:

1.1. Direct fusion with cell membraneDirect fusion with cell membrane

2.2. Endocytosis through a clathrin coated pitEndocytosis through a clathrin coated pit

2.2. Uncoating:Uncoating: Separation of viral nucleic acid from Separation of viral nucleic acid from protein capsid. Lysosomal, cytoplasmic, or viral protein capsid. Lysosomal, cytoplasmic, or viral enzymes may be involved.enzymes may be involved.

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

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

capsid and envelope proteinscapsid 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 main mechanisms of releaseThere are two 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. Budding:B. 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

Life Cycle of a DNA VirusLife Cycle of a DNA Virus

Life Cycle of BacteriophagesLife Cycle of BacteriophagesLytic Cycle: Lytic Cycle: Cell bursts at end of cycleCell bursts at end of cycle

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

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

3. 3. Biosynthesis:Biosynthesis: Viral proteins and nucleic acids are made. Viral proteins and nucleic acids are made.

4. 4. MaturationMaturation:: Bacteriophage capsids and DNA are Bacteriophage capsids and DNA are assembled into complete virions.assembled into complete virions.

5. 5. ReleaseRelease:: Bacteriophage virions are released from the cell. Bacteriophage virions are released from the cell. Plasma membrane breaks open and cell lyses. Plasma membrane breaks open and cell lyses.

Burst timeBurst time: Time from attachment to release of new virion : Time from attachment to release of new virion (20-40 minutes).(20-40 minutes).Burst sizeBurst size: Number of new phage particles that emerge from : Number of new phage particles that emerge from a single cell (50-200).a single cell (50-200).

Lytic Cycle of BacteriophageLytic Cycle of Bacteriophage

Lytic Cycle of BacteriophageLytic Cycle of Bacteriophage

Life Cycle of BacteriophagesLife Cycle of BacteriophagesLysogenic CycleLysogenic Cycle

1. Attachment and Penetration1. Attachment and Penetration: Virus tail : Virus tail binds to specific receptors on the cell binds to specific receptors on the cell surface and injects genetic material surface and injects genetic material (DNA) into cell. (DNA) into cell.

2. Circularization2. Circularization: Phage DNA circularizes : Phage DNA circularizes and enters either lytic or lysogenic cycle.and enters either lytic or lysogenic cycle.

Lysogenic CycleLysogenic Cycle3. Integration3. Integration: Phage DNA integrates with : Phage DNA integrates with

bacterial chromosome and becomes a bacterial chromosome and becomes a prophageprophage. Prophage remains . Prophage remains latentlatent..

4. Excision4. Excision: Prophage DNA is removed due : Prophage DNA is removed due to a stimulus (e.g.: chemicals, UV to a stimulus (e.g.: chemicals, UV radiation) and initiates a lytic cycle. radiation) and initiates a lytic cycle.

Lysogenic versus Lytic Cycles of BacteriophageLysogenic versus Lytic Cycles of Bacteriophage

Retroviruses Convert RNA into DNA via Retroviruses Convert RNA into DNA via Reverse TranscriptaseReverse Transcriptase

How does our body respond to viruses?How does our body respond to viruses?www.scripps.edu/community/lessonplans/Gibson%201.pptwww.scripps.edu/community/lessonplans/Gibson%201.ppt - - Amerika SerikatAmerika Serikat

Immunobiology, 5th ed. Janeway

HUMAN IMUNODEFICIENCY VIRUS HUMAN IMUNODEFICIENCY VIRUS (HIV)(HIV)

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A typical, "minimal" retrovirus consists of: • an outer envelope which was derived from the plasma membrane of its host• copies of an envelope protein embedded in the lipid bilayer of its envelope• a capsid; a protein shell• two molecules of RNA and •molecules of the enzyme reverse transcriptase

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RetrovirusRetrovirus

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Viruses are host specific – a protein on the surface of the virus has a shape that matches a molecule in the plasma membrane of its host, allowing the virus to lock onto the host cell.

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HIVHIV doesn’t target just any cell, it goes doesn’t target just any cell, it goes right for the cells that want to kill it. right for the cells that want to kill it. “Helper" T cells are HIV's primary “Helper" T cells are HIV's primary target. These cells help direct the target. These cells help direct the immune system's response to various immune system's response to various pathogens.pathogens.

The HIV in humans can only bind and fuse to the white blood cells, so therefore it lowers The HIV in humans can only bind and fuse to the white blood cells, so therefore it lowers the CD4+ count and in turn, the efficiency of the immune system. Also, since the virus the CD4+ count and in turn, the efficiency of the immune system. Also, since the virus can only infect the white blood cells, it cannot be transmitted by touch or by inhalation. can only infect the white blood cells, it cannot be transmitted by touch or by inhalation.

Once a white blood cell is infected, the human immune system tries to build up its Once a white blood cell is infected, the human immune system tries to build up its stamina in order to fight the disease; however, it is during this first period that the HIV stamina in order to fight the disease; however, it is during this first period that the HIV virus is able to replicate extensively. After this first period of time, the immune system virus is able to replicate extensively. After this first period of time, the immune system brings the virus under control and levels off the dropping number of CD4 cells. This time brings the virus under control and levels off the dropping number of CD4 cells. This time period is when humans may live for long amounts of time without any outside effects or period is when humans may live for long amounts of time without any outside effects or illness. illness.

Although the number of CD4 cells is now stable, the HIV virus continues to multiply & Although the number of CD4 cells is now stable, the HIV virus continues to multiply & infect. This is called the asymptomatic stage of infection. By this time, the amount of infect. This is called the asymptomatic stage of infection. By this time, the amount of CD4+ T cells being destroyed almost equal to the amount of viruses destroyed. This "full-CD4+ T cells being destroyed almost equal to the amount of viruses destroyed. This "full-scale war" between the two has roughly 10 billion virus particles being made and scale war" between the two has roughly 10 billion virus particles being made and destroyed and roughly 1 billion CD4+ T cells being killed and replaced each day. destroyed and roughly 1 billion CD4+ T cells being killed and replaced each day.

This dynamic equilibruim lasts for about 10 years or so until the enitre immune system This dynamic equilibruim lasts for about 10 years or so until the enitre immune system collapses, and the beginning of the onset of AIDS. The cause of death can range from collapses, and the beginning of the onset of AIDS. The cause of death can range from Tuberculosis to mold infections that affect the brain, liver, or intestines. (Tuberculosis to mold infections that affect the brain, liver, or intestines. (e.g.Cryptococcus e.g.Cryptococcus meningitismeningitis, Toxoplasmosis brain abscesses, gastroenteritis etc.) to cancers caused by , Toxoplasmosis brain abscesses, gastroenteritis etc.) to cancers caused by viruses. viruses.

HIV undermines the body's ability to protect against disease by HIV undermines the body's ability to protect against disease by depleting T cells thus destroying the immune system.The virus can depleting T cells thus destroying the immune system.The virus can infect 10 billion cells a day, yet only 1.8 billion can be replaced daily.infect 10 billion cells a day, yet only 1.8 billion can be replaced daily.

After many years of a constant battle, the body has insufficient After many years of a constant battle, the body has insufficient numbers of T-Cells to mount an immune response against numbers of T-Cells to mount an immune response against infections. At the point when the body is unable to fight off infections. At the point when the body is unable to fight off infections, a person is said to have the disease infections, a person is said to have the disease AIDSAIDS..

It is not the virus or the disease that ultimately kills a person; it is the It is not the virus or the disease that ultimately kills a person; it is the

inability to fight off something as minor as the common cold. inability to fight off something as minor as the common cold.

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To date, there has been no discovery of a treatment To date, there has been no discovery of a treatment which is capable of either totally prohibiting or eliminating which is capable of either totally prohibiting or eliminating the HIV/AIDS virus and is effective and useful for humansthe HIV/AIDS virus and is effective and useful for humans

These are different targets where one could These are different targets where one could Fight and possibly kill the HIV virus. Fight and possibly kill the HIV virus.

1. Binding of HIV to membrane of target cells. 1. Binding of HIV to membrane of target cells.

2. Inhibiting the reverse transcriptase (converts HIV RNA to DNA) 2. Inhibiting the reverse transcriptase (converts HIV RNA to DNA)

3. Inhibiting the enzyme that degrades HIV RNA after conversion 3. Inhibiting the enzyme that degrades HIV RNA after conversion to DNA to DNA

4. Inhibiting the actions of HIV integrase that integrates HIV DNA into 4. Inhibiting the actions of HIV integrase that integrates HIV DNA into host cells host cells

5. Inhibiting the expression of HIV genetic material once integrated into 5. Inhibiting the expression of HIV genetic material once integrated into the host cell the host cell

6. Inhibiting protease that splices proteins for assembling new virus 6. Inhibiting protease that splices proteins for assembling new virus particles. particles.

There are three drug types existing that are used in There are three drug types existing that are used in treating HIVtreating HIV. .

Nucleoside reverse transcriptase inhibitors (Example- Nucleoside reverse transcriptase inhibitors (Example- AZT, etc). These are the most well developed and widely AZT, etc). These are the most well developed and widely studied medications. These function by interfering with studied medications. These function by interfering with the reverse transcriptase enzyme while the viral RNA is the reverse transcriptase enzyme while the viral RNA is being transcribed to DNA. The virus functions by causing being transcribed to DNA. The virus functions by causing a termination in the chain of nucleic acid as it is being a termination in the chain of nucleic acid as it is being assembled. Early treatment with AZT has been proved to assembled. Early treatment with AZT has been proved to establish longer survival times except long term use can establish longer survival times except long term use can result in horrible long term irreversible side effects as result in horrible long term irreversible side effects as well as short term side effects such as headache, well as short term side effects such as headache, diaherra, muscle pain, fever, insomnia. diaherra, muscle pain, fever, insomnia.

Non-nucleoside reverse transcriptase inhibitors. Non-nucleoside reverse transcriptase inhibitors. (Example- Delavidine, nevirapine) These function similar (Example- Delavidine, nevirapine) These function similar to the reverse transcriptase inhibitors except they to the reverse transcriptase inhibitors except they terminate the nucleic acid chain at an earlier site. terminate the nucleic acid chain at an earlier site.

Protease inhibitors, which are called AIDS cocktails. Protease inhibitors, which are called AIDS cocktails. (Example-Saquinavir, Ritonavir, Crxivan) They disrupt (Example-Saquinavir, Ritonavir, Crxivan) They disrupt the HIV replication cycle as well, except at a different the HIV replication cycle as well, except at a different point. Protease is another enzyme essential to the point. Protease is another enzyme essential to the replication of the virus. Without it, the formation and replication of the virus. Without it, the formation and organization of virus proteins remains incomplete, organization of virus proteins remains incomplete, rendering the virus particles inactive. rendering the virus particles inactive.

Nucleocides interfere with the virus nucleotides before Nucleocides interfere with the virus nucleotides before they enter the nucleus of the cell and are processed as they enter the nucleus of the cell and are processed as proteins. Protease Inhibitors, on the other hand, proteins. Protease Inhibitors, on the other hand, interfere with the assembly of the proteins after they interfere with the assembly of the proteins after they are processed. The problem with all of these drugs is are processed. The problem with all of these drugs is that the virus changes so often and so rapidly. It is that the virus changes so often and so rapidly. It is almost a guess as to how the virus will change, this is almost a guess as to how the virus will change, this is the reason why "drug cocktails" are used most often to the reason why "drug cocktails" are used most often to fight the HIV virus. fight the HIV virus.

The main problem with the current treatments is that The main problem with the current treatments is that the HIV virus mutates quickly and that can render the the HIV virus mutates quickly and that can render the treatments ineffective. Rather than trying to conquer treatments ineffective. Rather than trying to conquer the constantly changing, our idea was to cover the the constantly changing, our idea was to cover the unchanging with a protective barrier. We ideally would unchanging with a protective barrier. We ideally would like to create a protein, with similar characteristics to a like to create a protein, with similar characteristics to a gp120 protein that would react with the CD4 cells in our gp120 protein that would react with the CD4 cells in our body thus preventing the HIV virus from reacting with body thus preventing the HIV virus from reacting with the CD4 and depositing nucleic acid. the CD4 and depositing nucleic acid.

The latest research on HIV treatment has to do with the The latest research on HIV treatment has to do with the subject of inhibiting binding to the human cells. The subject of inhibiting binding to the human cells. The proteins found in starfish inhibited the infection of proteins found in starfish inhibited the infection of human T-lymphoblastoid cells by HIV-1 in vitro with an human T-lymphoblastoid cells by HIV-1 in vitro with an EC50 of approximately 4 ng/mL. However, it was toxic EC50 of approximately 4 ng/mL. However, it was toxic in the human body. The new challenge is to find in the human body. The new challenge is to find something that will not be toxic in humans but contains something that will not be toxic in humans but contains the same proteins, thus performing the same duties as the same proteins, thus performing the same duties as the starfish protein on human CD4 cells. the starfish protein on human CD4 cells.

What is not known What is not known

It is not known how this starfish protein can be used in It is not known how this starfish protein can be used in humans as it is because because it is toxic. It is also humans as it is because because it is toxic. It is also unknown how to make it non-toxic. Research should be unknown how to make it non-toxic. Research should be done on how this protein could be altered, hopefully at just done on how this protein could be altered, hopefully at just one point in the genetic code, to account for the difference. one point in the genetic code, to account for the difference.

While researching nutritional information on HIV it was While researching nutritional information on HIV it was found that those patients who had a healthier diet had an found that those patients who had a healthier diet had an increased number of t-cells. Also a startling phenomenon increased number of t-cells. Also a startling phenomenon was discovered--(suspense rises) there is an entire body was discovered--(suspense rises) there is an entire body protein turn-over--this means liberated amino acids were protein turn-over--this means liberated amino acids were converted to synthesize new protein. Is it possible that the converted to synthesize new protein. Is it possible that the body is trying to produce new gp 120 proteins to block the body is trying to produce new gp 120 proteins to block the CD4 receptor sites? CD4 receptor sites?

Also, another amazing trend has appeared... the t-cell Also, another amazing trend has appeared... the t-cell count for HIV infected patients decreases rapidly for 3 count for HIV infected patients decreases rapidly for 3 months and increases back to normal levels in the months and increases back to normal levels in the following three months. following three months.

What are vaccines?What are vaccines?www.scripps.edu/community/lessonplans/Gibson%201.pptwww.scripps.edu/community/lessonplans/Gibson%201.ppt - - Amerika SerikatAmerika Serikat

A vaccine is a substance that stimulates the body’s A vaccine is a substance that stimulates the body’s immune response.immune response.

The goal of vaccination is to prevent or control an The goal of vaccination is to prevent or control an infection. infection.

A A vaccinevaccine is an is an antigenicantigenic preparation used to establish preparation used to establish immunityimmunity to a disease. to a disease.

Vaccines can be Vaccines can be prophylacticprophylactic (e.g. to prevent or (e.g. to prevent or ameliorate the effects of a future ameliorate the effects of a future infectioninfection by any natural by any natural or "wild" or "wild" pathogenpathogen), or ), or therapeutictherapeutic (e.g. vaccines against (e.g. vaccines against cancer are also being investigated; see cancer are also being investigated; see cancer vaccinecancer vaccine

There are four types of traditional There are four types of traditional

vaccinesvaccines Vaccines containing killed microorganisms - these are Vaccines containing killed microorganisms - these are previously virulent micro-organisms that have been killed with previously virulent micro-organisms that have been killed with chemicals or heat. Examples are vaccines against chemicals or heat. Examples are vaccines against fluflu, , choleracholera, , , , and and hepatitis Ahepatitis A. .

Vaccines containing live, Vaccines containing live, attenuatedattenuated microorganisms - these microorganisms - these are live micro-organisms that have been cultivated under are live micro-organisms that have been cultivated under conditions that disable their virulent properties. They typically conditions that disable their virulent properties. They typically provoke more durable immunological responses and are the provoke more durable immunological responses and are the preferred type for healthy adults. Examples include preferred type for healthy adults. Examples include yellow feveryellow fever, , measlesmeasles, , rubellarubella, and , and mumpsmumps. .

ToxoidsToxoids - these are inactivated toxic compounds from micro- - these are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organisms in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based organism itself) cause illness. Examples of toxoid-based vaccines include vaccines include tetanustetanus and and diphtheriadiphtheria. .

SubunitSubunit - rather than introducing an inactivated or attenuated - rather than introducing an inactivated or attenuated micro-organism to an immune system, a fragment of it can micro-organism to an immune system, a fragment of it can create an immune response. Characteristic examples include create an immune response. Characteristic examples include the subunit vaccine against the subunit vaccine against HBVHBV that is composed of only the that is composed of only the surface proteins of the virus (produced in surface proteins of the virus (produced in yeastyeast) and the ) and the virus-like particlevirus-like particle (VLP) vaccine against (VLP) vaccine against human papillomavirushuman papillomavirus (HPV) that is composed of the viral major (HPV) that is composed of the viral major capsidcapsid protein. protein.

An Innovative vaccines An Innovative vaccines are also in development and in use:are also in development and in use:

ConjugateConjugate - certain bacteria have - certain bacteria have polysaccharidepolysaccharide outer coats that outer coats that are poorly immunogenic. By linking these outer coats to proteins are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the (e.g. toxins), the immune systemimmune system can be led to recognize the can be led to recognize the polysaccharide as if it were a protein antigen. This approach is polysaccharide as if it were a protein antigen. This approach is used in the used in the Haemophilus influenzaeHaemophilus influenzae type B vaccine. type B vaccine.

RecombinantRecombinant Vector - by combining the physiology of one micro- Vector - by combining the physiology of one micro-organism and the organism and the DNADNA of the other, immunity can be created of the other, immunity can be created against diseases that have complex infection processes against diseases that have complex infection processes

DNA vaccinationDNA vaccination - in recent years a new type of vaccine, created - in recent years a new type of vaccine, created from an infectious agent's DNA called from an infectious agent's DNA called DNA vaccinationDNA vaccination, has been , has been developed. It works by insertion (and developed. It works by insertion (and expressionexpression, triggering , triggering immune system recognition) into human or animal cells, of viral or immune system recognition) into human or animal cells, of viral or bacterial DNA. Some cells of the immune system that recognize bacterial DNA. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the encountered at a later time, they will be attacked instantly by the immune system. One advantage of DNA vaccines is that they are immune system. One advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is very easy to produce and store. As of 2006, DNA vaccination is still experimental, but shows some promising results. still experimental, but shows some promising results.

Influenza VirusInfluenza Virus

Influenza A virus is essentially an avian virus that has "recently" Influenza A virus is essentially an avian virus that has "recently" crossed into mammals. Birds have the greatest number and range of crossed into mammals. Birds have the greatest number and range of influenza strains. Avian haemagglutinins sometimes appear in pig influenza strains. Avian haemagglutinins sometimes appear in pig human and horse influenza strains.human and horse influenza strains.

Every now and then (10 - 15 years) a major new pandemic strain Every now and then (10 - 15 years) a major new pandemic strain appears in man, with a totally new HA and sometimes a new NA as appears in man, with a totally new HA and sometimes a new NA as well well (antigenic shift).(antigenic shift). This variant causes a major epidemic around This variant causes a major epidemic around the world (pandemic). the world (pandemic).

Over the subsequent years this strain undergoes minor changes Over the subsequent years this strain undergoes minor changes (antigenic drift) (antigenic drift) every two to three years, probably driven by every two to three years, probably driven by selective antibody pressure in the populations of humans infected. selective antibody pressure in the populations of humans infected.

The avian influenzavirus subtypes that have been confirmed in The avian influenzavirus subtypes that have been confirmed in humanshumans, ordered by the number of known human deaths, are: H1N1 , ordered by the number of known human deaths, are: H1N1 caused caused Spanish fluSpanish flu, H2N2 caused , H2N2 caused Asian FluAsian Flu, H3N2 caused , H3N2 caused Hong Kong FluHong Kong Flu, , H5N1H5N1 is the current is the current pandemicpandemic threat, H7N7, H9N2, threat, H7N7, H9N2, H7N2, H7N3.H7N2, H7N3.

The virion is generally rounded but may be long and The virion is generally rounded but may be long and filamentous.filamentous.A A single-stranded RNAsingle-stranded RNA genome is closely associated genome is closely associated with a helical with a helical nucleoprotein (NPnucleoprotein (NP),), and is present in and is present in eight separate segments of eight separate segments of ribonucleoprotein (RNPribonucleoprotein (RNP),), each of which has to be present for successful each of which has to be present for successful replication. The segmented genome is enclosed within an replication. The segmented genome is enclosed within an outer lipoprotein outer lipoprotein envelopeenvelope. An antigenic protein called . An antigenic protein called thethe matrix protein (MP 1)matrix protein (MP 1) lines the inside of the lines the inside of the envelope and and is chemically bound to the RNP. The envelope and and is chemically bound to the RNP. The envelope carries two types of protruding spikes. One is a envelope carries two types of protruding spikes. One is a box-shaped protein, called the box-shaped protein, called the neuraminidase (NA),neuraminidase (NA), of of which there are nine major antigenic types, and which which there are nine major antigenic types, and which has enzymic properties as the name implies. has enzymic properties as the name implies.

The other type of envelope spike is The other type of envelope spike is a trimeric protein called the a trimeric protein called the haemagglutinin (HAhaemagglutinin (HA) ) (illustrated on the right) of which there are 15 major (illustrated on the right) of which there are 15 major antigenic types. The haemagglutinin functions during antigenic types. The haemagglutinin functions during attachment of the virus particle to the cell membrane, and attachment of the virus particle to the cell membrane, and can combine with specific receptors on a variety of cells can combine with specific receptors on a variety of cells including red blood cells. The lipoprotein envelope makes including red blood cells. The lipoprotein envelope makes the virion rather labile - susceptible to heat, drying, the virion rather labile - susceptible to heat, drying, detergents and solvents. detergents and solvents.

Neuraminidase

Haemaglutinin

RNA

M proteinOnly in Type A

Avian influenza virus spreads in the air and in manure and survives longer Avian influenza virus spreads in the air and in manure and survives longer in cold weather. It can also be transmitted by contaminated feed, water, in cold weather. It can also be transmitted by contaminated feed, water, equipment and clothing; however, there is no evidence that the virus can equipment and clothing; however, there is no evidence that the virus can survive in well cooked meat. The incubation period is 3 to 5 days. survive in well cooked meat. The incubation period is 3 to 5 days. Symptoms in animals vary, but virulent strains can cause death within a few Symptoms in animals vary, but virulent strains can cause death within a few days.days.

H5N1 H5N1 H5N1 is a highly pathogenic form of avian influenzavirus. Since H5N1 is a highly pathogenic form of avian influenzavirus. Since

1997, outbreaks of H5N1 flu have caused the death or culling of 1997, outbreaks of H5N1 flu have caused the death or culling of tens of millions of birds. Over 100 people have been infected by tens of millions of birds. Over 100 people have been infected by H5N1, with a mortality rate of over 50%. H5N1 has been the focus H5N1, with a mortality rate of over 50%. H5N1 has been the focus of much concern amid warnings that the H5N1 strain will likely of much concern amid warnings that the H5N1 strain will likely evolve into a form that causes a global human pandemic with a evolve into a form that causes a global human pandemic with a very high mortality rate. As of November 1, 2005, 122 cases of very high mortality rate. As of November 1, 2005, 122 cases of infections in humans, resulting in 62 deaths, have been confirmed infections in humans, resulting in 62 deaths, have been confirmed outside of China. outside of China.

Antiviral drugs such as oseltamivir, zanamivir and amantadine are Antiviral drugs such as oseltamivir, zanamivir and amantadine are sometimes effective in both preventing and treating the infection. Countries sometimes effective in both preventing and treating the infection. Countries have been stockpiling olestamivir, but may shift towards zanamivir due to have been stockpiling olestamivir, but may shift towards zanamivir due to issue, which reported oseltamivir resistant strains of avian flu in Vietnam.issue, which reported oseltamivir resistant strains of avian flu in Vietnam.

Flu vaccines, however, take at least four months to produce and must be Flu vaccines, however, take at least four months to produce and must be prepared for each subtype.prepared for each subtype.