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kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
kurdish information about virus 2014
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kurdish information about virus 2014

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kurdish information about virus 2014

kurdish information about virus 2014

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  • These two lectures will review some features of viruses from the basic virology to the development of immunity to virus infections.
  • Lecture 1
    Primarily concerned with the basic details of virus replication and pathogenesis.
  • Lecture 2
    Development of the immune response
  • What is a virus
    “Sub microscopic entities consisting of a single nucleic acid surrounded by a protein coat and capable of replication only within the living cells of bacteria, animals or plants.”[1]
    The key features of this definition are as follows:
                 Single type of nucleic acid – either DNA or RNA but not both
                 Replication of the virus only with a living cell – they are obligate intracellular parasites.
    These characteristics are typical for ALL viruses whether they infect bacteria, plants or animals. [1] Adapted from Collins English Dictionary
  • What is a virus
    “Sub microscopic entities consisting of a single nucleic acid surrounded by a protein coat and capable of replication only within the living cells of bacteria, animals or plants.”[1]
    The key features of this definition are as follows:
                 Single type of nucleic acid – either DNA or RNA but not both
                 Replication of the virus only with a living cell – they are obligate intracellular parasites.
    These characteristics are typical for ALL viruses whether they infect bacteria, plants or animals. [1] Adapted from Collins English Dictionary
  • <number>
             This overhead shows the standard features found in some (but not all) viruses.
             A virus particle is essentially a piece of nucleic acid surrounded by a protein coat.
             The protein coat (i.e. the capsid) is a delivery system for transferring the virus genome from one cell to another. The protein serves to:
         Provide protection to the nucleic acid against the environment - e.g. nucleases etc.
         Function in receptor recognition - targeting a virus to a susceptible host and cell type.
             Surrounding this coat there may be a lipid envelope - this envelope is derived from one of the cell membranes and is not determined by the virus. There may be some modification to the lipid composition induced during virus maturation.
             Inserted into the lipid envelope there are usually virus proteins which are present as spike projections - these are normally glycoproteins.
    Due to restrictions on the coding size of many virus genomes the capsid of the virion is made up of repeating subunits, which coat the virus genomic nucleic acid. The redundancy also allows for the fact that if there is an inactivation of part of the capsid the virus does not completely lose its infectivity For example the poliovirus RNA (7kb) can specific at most 250,000 Daltons of protein altogether (some must be used for replication) but the poliovirus virion capsid weighs 6 x 106 Daltons.
    Genomic Nucleic Acid
    Viruses only possess a single type of genomic nucleic acid – either DNA or RNA but not both. This nucleic acid can be in a variety of physicla forms that can be used as a valuable classification feature.
  •          The virions that you will see have the following common features:
    Simple structure
             The overall structure is not in general complex although they do perform complex functions (protection of the genome and entry of the virus to the cell)
    Repeating structure
             They are generally made up a very few proteins (the simple plant viruses may just have one protein in the virus capsid) OR proteins which are structurally very similar.
    High Level of Redundancy
    There is a high degree of redundancy in the virion, which allows for the partial inactivation of some parts of the virion without actually destroying the virion completely. The general exceptions to these comments are the poxviruses.
  • 1.1.         Virion Types
             The majority of viruses fall within one of two basic structures:
         Helical virions
         Icosahedral virions
             The features of each of these are described in the following.
    1.1.1.      Helical Virions
             Common form of structure in which the capsomeres wrap around the nucleic acid to produce a helix. In plant viruses this helix may be “naked” whereas in the case of viruses infecting animals all viruses have an envelope surrounding the capsid structure.
             The diameter of the helical capsid is determined by the characteristics of the capsomeres and the length of the nucleic acid molecule determines the length of the helix.
    1.1.2.      Icosahedral Virions
             The only closed shell that can be made with repeating capsomeres is an icosahedron. The simplest icosahedron is a regular solid with 12 vertices and 20 triangular faces - to make this shell there must be sixty identical protomers (i.e. 3 per face)[2].
             Larger viruses have a more complex virion. Each triangular face of the icosahedron is divided into six half-triangles. The corners of the inscribed faces are solid lines; those of the basic faces are dashed lines. Monomers are arranged in pentons around the fivefold axis and in hexons around the threefold axis. In the case of poliovirus each of the sixty subunits is made up of three monomers VP1, VP2 and VP3.
             In higher order capsids still the proteins located at the pentons and hexons are distinct proteins - for example in adenovirus the hexons contain three protomers rather than six as in the basic icosahedron.
             Icosahedral particles may exist as either naked or enveloped virions.
    [1] Naked viruses with helical virions (e.g. plant viruses) are more tightly packed.
    [2] The smallest and simplest virions made up of 60 identical subunits are that of satellite tobacco mosaic virus. Possess a short RNA (~1600 bases) with just one gene that encoding the capsid protein. This virus can only replicate in cells already infected by tobacco necrosis virus. This virus is referred to as a satellite virus.
    1.1.1.      Complex virions
    Not all viruses fall within these two simple categories and two examples will be given of so-called complex virions.
  • <number>
    There are many variations on the virus replication and this diagram illustrates some of the basic features of the cycle.
    1.             Attachment and entry: viruses recognise specific structures on the cell surface (referred to as virus receptors), which target the virus to specific cell types and tissue. This is one of the primary determinants for which tissues are infected by a particular virus. The receptor is a normal component of the cell, which the virus has hijacked for the infection process.
    2.             Uncoating: The virion breaks open and releases the virus genome nucleic acid into the host cell cytoplasm. Further replication may take place in the cytoplasm or the nucleic acid may migrate to the cell’s nucleus.
    3.             Transcription: Virus mRNA is produced using either cellular enzymes or virus-coded enzymes.
    4.             Genome replication: This stage can take place in either the cytoplasm or nucleus of the infected cell. Depending on the size of the virus genome the enzymes involved in genome replication may be encoded by either the virus itself or the host cell.
    5.             Translation: This stage uses the host cell machinery - ribosomes and enzymes etc. Various proteins are synthesised - structural - only in virion - and non-structural - detected only in the virus-infected cell.
    6.             Virion Assembly: The newly formed virus proteins and genomic nucleic acid assemble to produce the new virus particles.
    7.             Virion release: Various strategies are available for the release of the progeny virus from the infected cell depending on the particular virus group. The virus may bud through the cell membrane at which time it picks up the envelope surrounding the virus particle OR the virus may simply cause lysis of the cell resulting in cell death and the release of progeny virus particles.
  • <number>
    Cell death – Cytopathic effect
             This is the end result of many lytic virus infections in which the cell is killed following virus infection. This end result of virus infection is the cause of cpe found in cell culture systems infected with lytic viruses. The form of virus-induced cpe can take many forms ranging from the lysis of the cell to a fusion event with the formation of syncytia.
    Persistent infection
             The outcome of some virus infections is not cell death but the development of a persistent (or chronic) virus infection. This differs from the transformation of cells (described below) since in many cases the cells appear similar (or identical) to the uninfected parental cell line. The cells may continue to grow in culture and release infectious virus.
             These infections are characterised by the virus normally being lytic but under specific situations (e.g. host cell type) the virus establishes a chronic or persistent infection.
    Latent Infection
             The capacity of herpes virus to establish a latent infection is essentially another form of persistent infection. In this case the virus is not actually replicating but lying dormant in the host cell
    Transformation
             A transformed cell in vitro or a tumour developing in vivo is essentially a cell-type, which shows no control over its cell division with unregulated growth.
  •          As with many infections viruses can be transmitted between susceptible individuals by a variety of means. The details provided related mainly to viruses infecting humans.
             Many animal viruses do not remain infectious for very long outside the host.
         Respiratory: Influenza A virus (and rhinovirus). Transmission in the form of aerosols during coughing and sneezing. The viruses are fairly sensitive to drying and their transmission is highest when individuals are in close contact.
         Faecal-oral: Enteroviruses (e.g. poliovirus) A lot of viruses are excreted in faeces following high levels of replication in the gut.
         Blood borne: Hepatitis B (and HIV). Transferred through contaminated blood products or via shared needles with drug abuse.
         Sexual transmission: (HIV)
    Animal/insect vector: Rabies. In many instances the virus infection is a specific pathogen of the animal and is not normally transmitted to humans by any other means.
  • An Importatnt statge in virus pathogenesis is the targetting of the virus for a specific tissue or cell type. This is achieved at the initial stage of virus replication when the virus recognises a receptor on the cell surface.
    There are various receptors defined for viruses and two are shown here:
    CD4+ cells are infected with HIV – these are largely T4 helper cells
    CD155 is the receptor for poliovirus and the pattern of the expression of this protein folows the specifi cells infected by poliovirus under natural conditions.
  •          The diseases caused by viruses are due to a number of mechanisms of which the major ones are as follows (these have analogies to the manner in which the virus interacts with cells in vitro):
                Cell destruction following virus infection: Essentially the virus infection leads to the death of the infected cells. This is equivalent to the cytopathic effect observed during the infection of cells in vitro.
                Virus-induced changes to cellular gene expression: The presence of the virus within the host cell may lead to virus-induced changes in the expression of specific cellular genes. This will be discussed further with respect to the occurrence of virus-induced tumours.
    Immunopathogenic disease: Some viruses may induce changes in the pattern of the immune response by the host - e.g. infection of specific cells in the immune system, altered exposure of host antigens to the immune system, disturbed expression of specific cytokines during virus infection.
  •          The graph illustrates the typical pattern of virus replication during an acute virus infection:
                Following a short incubation period of a few days there a maximal virus production
                Visible symptoms generally appear just after this peak of virus replication. Depending on the virus the symptoms may last just a few days.
                The patient recovers and an immune response is generated and the virus is eliminated within 1 or 2 weeks.
            
  •          The spread of virus during acute virus infection can be variable with two general patterns:
                Localised to specific site of body: The virus infects at a specific site of the body and does not spread beyond that site - i.e. little or no viraemia.
    Development of viraemia with widespread infection of tissues: The virus can infect at one site in the body but develops a viraemia with extensive spread beyond the initial entry to cause a number of diverse disease symptoms.
  •          A human virus infection that is largely controlled by vaccination and is likely to be fully eradicated in the next few years.
    The infection here is associated with infantile paralysis affecting the lower limbs but in severe cases there can be paralysis of the muscles controlling respiration.
  • Enterovirus.
    Possesses a RNA genome.
    Transmitted by the faecal oral route.
    Cause of gastrointestinal illness and poliomyelitis.
  •          The main features of an enterovirus infection are as follows:
         The virus is transmitted by the faecal oral route and is ingested from contaminated food or water - the contamination of these sources is due to the excretion of virus in the faeces of an infected individual.
         The initial site of infection is the gut and in the majority of cases (ca 90% for poliovirus) the virus does not spread further and the infection may be inapparent.
         The virus can spread beyond the initial site of infection as a viraemia with virus spread via the blood and lymph.
         During the viraemia the virus can infect tissues beyond the initial site of entry - e.g. non-neuronal tissues (heart for CBV) as well as neuronal tissues.
    Enteroviruses are an important cause of aseptic meningitis and in the case of neuronal infections by poliovirus there can be severe paralysis leading to fatalities.
  • The incidence of poliovirus is declining and is due for complete eradication in the next 5-10 years.
    This has been achieved by the use of two vaccines for poliovirus.
    Salk Vaccine: The first to be produced. This is a killed vaccine in which the virus is no longer able to replicate but it can still act as an antigen to stimulate an immune response in the vaccinee.
    Sabin vaccine: Here the virus is alive but attentiated – I.e. it can replicate but does not produce disese. It can still induce an immune response. This is the most widelty used vaccine particurlt in the UK. It produces the most efficient immune response.
  • Influenza A virus is the second acute infection to be discussed.
    Myxovirus
    Enveloped virus with a segmented RNA genome
    Infects a wide range of animals other than humans
    Undergoes extensive antigenic variation
    Major cause of respiratory infections
  • Respiratory aerosoles can be generated from the respiratory tract by various means – from speaking to sneezing.
    During a sneeze, millions of tiny droplets of water and mucus are expelled at about 200 miles per hour (100 metres per second). The droplets initially are about 10-100 micrometres diameter, but they dry rapidly to droplet nuclei of 1-4 micrometres, containing virus particles or bacteria. This is a major means of transmission of several diseases of humans.
  • There are various means by which the host is protected from infection by influenza virus.
    The droplets containg the virus may be filtered by fines hairs and cilia in the nasal cavity.
    Muco-cilliary cells lining the trachea can trap virus particles and sweep the virus to the back of the throat from where it is swallowed and excreted via the intestinal tract.
    Alveolar macrophages can engulf the virus if it enteres as far as the lower reaches of the lung and alveolar sac.
  • Virus epidemiology
    Infleunza A virus shows regular outbreaks during the winger months.
    These are either
    Eopidenics: widespread outbreaks within the coutry
    Pandemics: Worldwide outbreaks of the virus affecting large numbers of people.
  • Epstein Barr Virus
    Burkitt’s Lymphoma
    Human papillomavirus
    Benign warts
    Cervical Carcinoma
    Human T-cell Lymphoma Virus (HTLV-1)
    Lekaemia
    Hepatitis C virus
    Liver carcinoma
  • <number>
    Virus trasnformed cells show a complete deregulation of their normal growth. They tend to pile up over each other and do not stop growing as is typical of normal uninfected/non-trasnformed cells.
    This change in the phenotype is due to the virus influencing the gene reulation of the cell. Many of the cellular genes affected that lead to the trasnformed pheotype are associated with gowth regulation and signal recognittion.
  •          The following points should be noted for virus-induced tumours:
                Virus infects cell: The infection process of an uninfected cell by the virus follows the standard pathway.
                Virus nucleic acid, as DNA, integrates into cellular genome: In the majority of virus tumours the virus nucleic acid integrates and physically joins with the cellular genome DNA. This contrasts with the HSV latent infection where the virus nucleic acid remains independent from the cellular genome.
    For retroviruses, which have RNA as their genomic nucleic acid, a DNA copy of the virus genome RNA is made.
    The virus may remain integrated with the cell for an extended period without any overt sign of infection.
                Virus causes changes in cellular gene expression: Because the virus nucleic acid is physically incorporated into the cell genome it can influence gene expression either through the introduction of new genes (already present in the virus genome) or by activating cell genes in an uncontrolled manner.
    Uncontrolled cell multiplication and tumour formation: The end result of the altered gene expression is the deregulation of cell growth with the formation of a tumour.
  • Antivirals
    Vaccines and immunisation
  • Attachment/Entry
    Picornaviruses
    Nucleic acid replication
    Human immunoideficiency virus (AZT)
    Herpes simplex virus (Acyclovir)
    Virus protein processing
    HIV (Protease inhbitors)
    Virus maturation
    Influenza A virus (Neuraminidase blockers)
    Problems of antivruals
    Dificuly in finding a virus specific site against which to direct the antivrial
    As with the use of antiiotics – resistant mutant scan be readily generated that are resistant to antiirals – this is particuarly a problem with those against HIV where the drug has to be used for prolonged periods of time.
  • Transcript

    • 1. Introduction to viruses
    • 2. Lecture topics - 1 • What is a virus?  Definition  Structure and replication • • Human virus infections Treatment  Antivirals  Vaccines
    • 3. Lecture topics – 2 • Immunity to viruses  Cell-mediated  Humoral • • Role of Complement Vaccination against viruses  Inactivated vaccines  Live vaccines • Interferon
    • 4. Definition of a Virus Sub microscopic entity consisting of a single nucleic acid surrounded by a protein coat and capable of replication only within the living cells of bacteria, animals or plants.
    • 5. Definition of a Virus Obligate Intracellular Parasite
    • 6. Virion Structure Lipid Envelope Nucleic Acid Protein Capsid Virion Associated Polymerase Spike Projections
    • 7. Virion Morphology • Simple Structure • Repetitive Structure • High Level of Redundancy
    • 8. Virus Morphology Helical Icosahedral
    • 9. Virus Replication 1 Virus attachment 1 2 3 5 2 4 5 6 4 3 7 8 7 6 8 and entry Uncoating of virion Migration of genome nucleic acid to nucleus Transcription Genome replication Translation of virus mRNAs Virion assembly Release of new virus particles
    • 10. Cytopathic Effect (cpe) Adenovirus Herpes virus
    • 11. Transmission of Viruses • • • • • Respiratory transmission  Influenza A virus Faecal-oral transmission  Enterovirus Blood-borne transmission  Hepatitis B virus Sexual Transmission  HIV Animal or insect vectors  Rabies virus
    • 12. Virus Tissue Tropism • Targeting of the virus to specific tissue and cell types • Receptor Recognition  CD4+ cells infected by HIV  CD155 acts as the receptor for poliovirus
    • 13. In vivo Disease Processes • Cell destruction • Virus-induced changes to gene expression • Immunopathogenic disease
    • 14. Acute Virus Infection Amount of virus Symptoms Virus Time
    • 15. Acute Virus Infections • Localised to specific site of body • Development of viraemia with widespread infection of tissues
    • 16. Poliovirus
    • 17. Poliovirus Properties of the virus • • • • Enterovirus. Possesses a RNA genome. Transmitted by the faecal oral route. Cause of gastrointestinal illness and poliomyelitis.
    • 18. Poliovirus Infection Virus Infection Gut Non-neuronal tissues Viraemia Neuronal tissues Virus excretion in the faeces Paralysis
    • 19. Incidence of Poliomyelitis Number of cases (in thousands) A B 40 Poliovirus vaccines A: Salk – killed inactivated vaccine. B: Sabin – live attenuated vaccine 30 20 10 0 1950 1960 1970 1980
    • 20. Influenza A virus Properties of the virus • • • • • Myxovirus Enveloped virus with a segmented RNA genome Infects a wide range of animals other than humans Undergoes extensive antigenic variation Major cause of respiratory infections
    • 21. Influenza A virus Infection • • • Spread by respiratory route Virus infects cells of the respiratory tract Destruction of respiratory epithelium  Secondary bacterial infections • Altered cytokine expression leading to fever  e.g interleukin-1 and interferon
    • 22. Spread of influenza virus
    • 23. Respiratory Tract
    • 24. Weekly consultation rates for influenza and influenza-like illness: Weekly Returns Service of the Royal College of General Practitioners, 1988 to 1999 Rate per 100 000 population 600 500 Epidemic activity 400 300 200 Higher than expected seasonal activity Baseline activity Normal seasonal activity 100 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Year CDR Weekly Report: 5th November 1999
    • 25. Generation of Novel Influenza A Viruses Human H2N2 ANTIGENIC SHIFT Genetic Reassortment Avian H3N8 Point mutation of HA and NA genes ANTIGENIC DRIFT Human H3N2
    • 26. Viruses and Human Tumours • Epstein Barr Virus  Burkitt’s Lymphoma • Human papillomavirus  Benign warts  Cervical Carcinoma • Human T-cell Leukaemia Virus (HTLV-1)  Leukaemia • Hepatitis C virus  Liver carcinoma
    • 27. Virus-induced tumours Virus Infection [ ] Uninfected Cell ? Uncontrolled cell growth and tumour formation
    • 28. Virus-induced transformation Normal cells Transformed cells
    • 29. Virus-Induced Tumours • • • • Virus infects cell. Virus nucleic acid, as DNA, integrates into cellular genome. Virus causes changes in cellular gene expression. Uncontrolled cell multiplication and tumour formation.
    • 30. Treatment and Prevention of Virus Infections • Antivirals • Vaccines and immunisation
    • 31. Antiviral Targets • Attachment/Entry • Nucleic acid replication • Virus protein processing • Virus maturation
    • 32. Problems with Antivirals • Identification of virus-specific target. • Generation of resistant variants.

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