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Virus i

Virus, infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The name is from a Latin word meaning “slimy liquid” or “poison.”

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VIRUS-I
Md. Saiful Islam
B.Pharm, M.Pharm (PCP)
North South University
Join Facebook Group: Pharmacy Universe
What is a virus ?
• Viruses are submicroscopic, obligate intracellular
parasites
• Morphologically, virus particle is a protein shell, in
which the viral genome is enclosed
• Virus particles are produced from the assembly of
pre-formed components and do not grow or
undergo division
• Viruses lack the genetic information which encodes
apparatus necessary for the generation of metabolic
energy and for protein synthesis
The Viruses-
• Can infect every type of cell
• Cannot exist independently from the host cell, so
aren’t considered living things
• However, since they can direct life processes they
are often considered more than lifeless molecules
• Referred to as infectious particles, either active or
inactive
• Obligate intracellular parasites
• Cannot multiply unless they invade a specific host
cell and instruct its genetic and metabolic
machinery to make and release new viruses
Virus i
Virus i
The Search ?
• Viruses were too small to be seen with the first
microscopes
• The cause of viral infections was unknown for years
• Louis Pasteur first proposed the term virus
• 1890s
– Iwanowski and Beijerinck showed that a disease in
tobacco was caused by a virus
– Loeffler and Frosch discovered an animal virus
that causes foot –and-mouth disease in cattle
• Many years of experimentation showed what we know
today and by the 1950s virology had grown

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Virus i

  • 1. VIRUS-I Md. Saiful Islam B.Pharm, M.Pharm (PCP) North South University Join Facebook Group: Pharmacy Universe
  • 2. What is a virus ? • Viruses are submicroscopic, obligate intracellular parasites • Morphologically, virus particle is a protein shell, in which the viral genome is enclosed • Virus particles are produced from the assembly of pre-formed components and do not grow or undergo division • Viruses lack the genetic information which encodes apparatus necessary for the generation of metabolic energy and for protein synthesis
  • 3. The Viruses- • Can infect every type of cell • Cannot exist independently from the host cell, so aren’t considered living things • However, since they can direct life processes they are often considered more than lifeless molecules • Referred to as infectious particles, either active or inactive • Obligate intracellular parasites • Cannot multiply unless they invade a specific host cell and instruct its genetic and metabolic machinery to make and release new viruses
  • 6. The Search ? • Viruses were too small to be seen with the first microscopes • The cause of viral infections was unknown for years • Louis Pasteur first proposed the term virus • 1890s – Iwanowski and Beijerinck showed that a disease in tobacco was caused by a virus – Loeffler and Frosch discovered an animal virus that causes foot –and-mouth disease in cattle • Many years of experimentation showed what we know today and by the 1950s virology had grown
  • 7. History • The first and foremost evidence of viruses responsible for causing human disease came into notice in 1892 when Iwanowski rightly demonstrated that the cell-free extracts of the diseased tobacco leaves passed through the bacteria-proof filters may ultimately cause disease in the ‘healthy plants’. • Such cell-free filtrates when cultured upon the bacterial growth media they eventually exhibited practically little growth thereby suggesting that the said filtrates contained the actual disease causing agents that are other than microorganisms.
  • 8. TMV (Tobacco mosaic virus) Pitch of helix 22.8 Å p=1.4Å (axial rise per subunit) m=16.3 (subunits per helix turn)
  • 9. History • Twort and d’Herrelle (1915) individually showed the ‘glassy phenomenon’ present very much in the microorganisms when it was observed clearly and distinctly that the bacterial cells might be adequately infected with and duly destroyed by the filterable agents, which in turn caused various serious diseases both affecting the animal kingdom and the plant kingdom. • Later on, these disease producing filterable agents are known as bacteriophages (i.e., the bacteria-eaters). • Wendell M Stanley (1935), an American Chemist, first and foremost isolated the tobacco mosaic virus (genus Tobamovirus) thereby making it possible to perform the chemical as well as structural studies on a purified virus.
  • 10. History • Interestingly, almost within the same time, the invention of the electron microscope took place which eventually made it quite possible to visualize the said viruses for the first time. • Latest molecular biology techniques in the 1980s and 1990s have remarkably led to the discovery of the new dreadful human viruses. • In the year 1989, the world has duly acknowledged the discovery of Hepatitis C virus, and Pestivirus, which specifically causes acute pediatric diarrhoea. • In1993, critically observed the outbreak of a Hantavirus infection occurring exclusively in the Southwestern USA, which essentially possesses the potential for new infections to emerge at any time. • Hantavirus disease refers to the acute ailment related to respirator disease and may even prove fatal.
  • 11. The Composition Common things to all virus particles: 1. It encloses genomic nucleic acid 2. It is a polymer, assembled from one or few different kinds of monomers
  • 12. Viral Structure • Genetic material of a virus is either DNA or RNA, but never both • Protein coat is called CAPSID; surrounds the nucleic acid core • Capsid is composed of sub-units called CAPSOMERES • Some viruses may have a lipid envelope around the outside • Envelope may or may not be covered with SPIKES
  • 13. The nucleocapsid • Nucleocapsid is the viral nuleic acid, enclosed in the protein shell • In case of simple non-enveloped viruses nucleocaspsid and virus particle is the same thing • In enveloped viruses, lipid bilayer of cellular origin encloses the nucleocapsid
  • 16. Enveloped and non-enveloped viruses • Non-enveloped virus • Enveloped virus DNA or RNA genome Nucleocapsid Lipid bilayer Envelope protein Matrix protein
  • 18. Functions of the Viral Envelope • Protects nucleic acids • Help introduce the viral DNA or RNA into a suitable host cell • Stimulate the immune system to produce antibodies that can protect the host cells against future infections
  • 19. Spikes • Hemagglutinin spikes • 500 per virus • Allows virus to recognize and attach to body cells • Antibodies made to these spikes • Neuraminidase spikes • 100 per virus • Help virus separate from infected host cell
  • 20. The genomes • I: Double-stranded DNA. Examples: Adenoviruses, Herpesviruses, Papillomaviruses, Poxiviruses,T4bacteriophage • II: Single-stranded (+)sense DNA. Examples: phage M13, chicken anaemia virus, maize streak virus • III: Double-stranded RNA. Examples:Reoviruses, Rotavirues Genome- the sum total of the genetic information carried by an organism
  • 21. The genomes • IV: Single-stranded (+)sense RNA Examples: Hepatitis A and C, Small RNA phages, common cold viruses, SARS (Severe acute respiratory syndrome).
  • 22. • V: Single-stranded (-)sense RNA. Examples: Influenza viruses, Hantaviruses . VI: Single-stranded (+)sense RNA with DNA intermediate in life-cycle (Retroviruses). Examples: HIV, Avian leukosis virus VII: Partial double-stranded (gapped) DNA with RNA intermediate (Hepadnaviruses) Example: Hepatitis B The genomes
  • 25. How Viruses are Classified and Named • Main criteria – Structure – Chemical composition – Similarities in genetic makeup • International Committee on the Taxonomy of Viruses, 2000 – 3 orders – 63 famillies “-viridae” – 263 genera “-virus”
  • 27. The viral life cycle •Initation phase: a) Attachment to the host cell receptor (Ig like receptors, cellular adhesion molecules, membrane transport proteins, oligosaccharides, etc) b) Penetration (endocytosis, fusion) c) Uncoating • Most bacteriophages avoid penetration and uncoating stages by injecting the viral nucleic acid into the cell. • Plant viruses do not use specific receptors and enter the cell either through insect vectors or mechanically damaged parts of plant. • Some viruses initiate direct cell fusing. In this process infected cell is fused with uninfected.
  • 29. The viral life cycle • Replication phase a) nucleic acid replication b) mRNA synthesis c) protein expression d) assembly • Release phase a) exit from cell (lysis, exocytosis, budding) b) maturation (rearrangement of nucleocapsid, etc)
  • 31. Satellites: small RNA molecules, absolutely dependent on presence of another virus Type A: an RNA molecule of more than 700 nt, which encodes its own capsid protein Type B: an RNA molecule of more than 700 nt, which encodes a non-structural protein Type C: a linear RNA of less than 700 nt, which does not encode any proteins Type D: a circular RNA of less than 700 nt, which does not encode any proteins NT: Abbreviation for nucleotide; i.e. the monomeric unit from which DNA or RNA are built. One can express the size of a nucleic acid strand in terms of the number of nucleotides in its chain; hence ‘nt’ can be a measure of chain length.
  • 32. Satellites • Satellites often cause different symptoms than the host virus alone • Most known satellites are associatet with plants (satellite tobaco necrosis virus, satellite panicum mosaic virus, etc) • Some are dependent on animal viruses – for example dependoviruses, wich are satellites of adenoviruses.
  • 33. Different symptoms of infection by Tobacco necrosis virus without (left) and with co- infection of Tobacco sattelite necrosis virus
  • 34. Viroids • Viroids are very small (200-400 nt) rod-like RNA molecules with a high degree of secondary structure • Viroids do not encode any proteins and unlike satellites they are not dependent on the presence of another virus
  • 35. Viroids • Infectious RNA • No protein coat • Naked pieces of RNA that cause disease • GOOD NEWS – viroids cause disease only in plants, at least so far!
  • 36. Examples of plants, infected with various viroids
  • 37. Hepatitis D virus – a chimeric molecule, half viroid, half satellite • Viroid like properties - Rod-like RNA molecule - Central conserved region similar to plant viroids - Rolling circle replication - Self-cleaving activity • Satellite like properties - Encodes a protein, which is necessary both for encapsidation and replication - Dependent on presence another virus – HBV - Genome larger than for viroids (1640 nt)
  • 38. Prions • Infectious proteins! • Naked protein molecules that cause disease and death in humans • Two well known prion diseases are SCRAPIE and MAD COW DISEASE • Human prion disease is variant Creutzfledt-Jakob disease • Disease causes fatal brain encephalitis
  • 39. Virus Replication 1 Virus attachment and entry 1 2 Uncoating of virion 2 3 Migration of genome nucleic acid to nucleus 3 4 Transcription 5 Genome replication 4 5 6 Translation of virus mRNAs 6 7 Virion assembly 7 8 Release of new virus particles 8
  • 40. 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.
  • 41. 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.
  • 43. How are viruses categorized? • Type of nucleic acid • How they replicate • Morphology
  • 44. Bacterial Viruses • Bacteriophage - from Greek phage in “to eat” • Viruses that ONLY infect most types of bacteria • Phages may be the most common entities in the biosphere • Two cycles of viral multiplication 1. LYTIC CYCLE 2.LYSOGENIC CYCLE
  • 45. 1.Lytic Cycle • 1. Attachment- binding sites must match receptor sites on host cell • 2. Penetration - viral DNA is injected into bacterial cell • 3. Biosynthesis – Genome replication – Transcription – Translation • 4. Assembly (Maturation) – viral particles are assembled • 5. Release – Lysis Virus uses Host Cells enzymes and machinery
  • 48. Lysogeny: The Silent Virus Infection • Temperate phages- special DNA phages that undergo adsorption and penetration but are not replicated or released immediately • Instead the viral DNA enters an inactive prophage stage • Lysogeny: the cell’s progeny will also have the temperate phage DNA • Lysogenic conversion: is a change that is induced the host phenotype by the presence of a prophage.
  • 49. 2. Lysogenic Cycle • 1. Attachment • 2. Penetration • 3. Integration – Viral Genome is integrated into Host Cell Genome – Virus is “Latent” – Prophage • 4. Biosynthesis - Viral Genome is Turned On – Genome replication – Transcription – Translation • 5. Assembly • 6. Release – Lysis
  • 50. Lysogenic Convergence • 1. Corynebacterium diphtheriae • 2. Streptococcus pyogenes – Scarlet Fever • 3. Clostridium botulinum
  • 52. Comparison of bacterial virus and animal virus multiplication • Bacterial – Attachment – Penetration – Biosynthesis – Maturation – Release • Animal – Attachment – Penetration – Uncoating – Biosynthesis – Maturation – Release
  • 54. Techniques in Cultivating and Identifying Animal Viruses • Primary purposes of viral cultivation – To isolate and identify viruses in clinical specimens – To prepare viruses for vaccines – To do detailed research on viral structure, multiplication cycles, genetics, and effects on host cells • Using Live Animal Inoculation – Specially bred strains of white mice, rats, hamsters, guinea pigs, and rabbits – Animal is exposed to the virus by injection • Using Bird Embryos – Enclosed in an egg- nearly perfect conditions for viral propagation – Chicken, duck, and turkey are most common – Egg is injected through the shell using sterile techniques
  • 55. Using Cell (Tissue) Culture Techniques • Most viruses are propagated in some sort of cell culture • The cultures must be developed and maintained • Animal cell cultures are grown in sterile chambers with special media • Cultured cells grow in the form of a monolayer • Primary or continuous
  • 57. Virus versus Virion • Virus is a broad general term for any aspect of the infectious agent and includes: • the infectious or inactivated virus particle • viral nucleic acid and protein in the infected cell • Virion is the physical particle in the extra-cellular phase which is able to spread to new host cells; complete intact virus particle
  • 59. Virus Structure • consist of a core of nucleic acid surrounded by a protein coat +/- envelope • components of virus particle include: i) nucleic acid - DNA or RNA - single - or double - stranded - intact / fragmented; linear / circular - encodes very few proteins
  • 60. Virus Structure ii) proteins: a) structural - capsid made of capsomeres - serve as antigens which elicit an immune response b) enzymes - differ from host cell - targets of antiviral therapy iii) envelope - found in some viruses; - lipoprotein envelope containing viral and host cell components - destroyed by lipid solvents
  • 64. Outcome of Viral Infections Virus-host cell interaction may result in: 1. Cell death (lytic) - due to cytopathic effect of virus 2. Cell transformation - cell converted to malignant or cancerous cell 3. Latent infection (occult) - persistent infection in quiescent state which may reactive anytime to produce disease; continuous or intermittent shedding 4. Cell fusion to form multinucleated cells
  • 65. Persistent Viral Infections 3 types of persistent viral infection (some overlap): 1. Chronic carrier - eg. Hepatitis B; results in chronic illness 2. Latent infection - eg. Herpesviridae; result in symptomatic or asymptomatic shedding 3. Slow virus infections - due to prolonged incubation period (eg. Measles virus and SSPE)