Introductory Virology. Ibrahim Jamfaru School of Medicine UHAS

Transcription

1 Introductory Virology Ibrahim Jamfaru School of Medicine UHAS

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3 Lecture outline Definition of viruses and general characteristics Structure of virus (virion) Chemical composition of viruses Virus morphology Reaction to physical & chemical agents

4 Definition Viruses are Unique, smallest heterogeneous infectious agents with sizes ranging from nm in general

5 Definition Contain only one kind of nucleic acid (RNA & DNA) They are obligate intracellular parasites grow in other living cells Lack energy-synthesizing organelles, enzyme systems and proteinsynthesizing machinery

6 General characteristics Viruses reproduce by assembling subunits into infectious particles, not by dividing as other microorganisms do (complex biosynthesis) Infectious particles of a virus is the virion

7 General characteristics They are not susceptible to antibiotics Susceptible to antimicrobial chemical agents e.g. chlorine, alcohol, formalin etc

8 General characteristics Viruses are known to infect unicellular organisms such as mycoplasmas, bacteria and algae They also infect higher plants and animal including insects

9 General characteristics Major virus groups are Plant viruses Insect viruses Viruses of bacteria (bacteriophage) Viruses of vertebrates (animal viruses)

10 Virus structure A virion which is the infectious particle has at least two components Molecules of either DNA or RNA referred to as the genome An outer symmetrical protein shell known as the capsid It therefore has a simple organization

11 Virus structure The nucleic acid and the capsid is referred to as the nucleocapsid Some viruses apart from the nucleocapsid may have extra membrane called the envelope

12 Virus structure Viruses made up of nucleocapsid alone are referred to as naked viruses Viruses with envelope are called enveloped viruses

13 VIRUS STRUCTURE

14 Chemical composition of viruses Viral nucleic acid Viral protein Capsid Enzymes Viral lipids Envelope

15 Chemical composition of viruses Viral glycoproteins NA and HA for attachment and pathogenesis

16 Chemical composition of viruses Nucleic acid which is made up of Adenine Guanine Cytosine Uracil and thymine Virus consists of either DNA or RNA

17 Nucleic Acid Constitutes the genome which carries the genetic information necessary for replication Nucleic acid may be Single or double stranded Circular or linear Segmented or non-segmented Positive or negative polarity

18 Nucleic Acid Each family of viruses possesses a nucleic acid characteristic for that group Sequence or composition of nucleotides can be analyzed using restriction nucleases

19 Nucleic acid All the animal RNA viruses are single stranded except the REO or DIPLO RNA viruses All the animal DNA viruses are double stranded except the PARVOVIRUSES

20 Viral Protein - Capsid The capsid is composed of individual polypeptides coded by the virus The number and appearance of capsomers are characteristic of a virus and important in its identification

21 Viral Protein - Capsid The capsid performs four functions It protects the nucleic acid from damage in the external environment Facilitates attachment to susceptible cells Confers structural symmetry on the virion Confers antigenicity

22 Viral Protein Enzymes Polymerase Integrase Reverse transcriptase

23 Viral Lipids: Envelope These are part of the envelope coded by the host cell

24 Viral Carbohydrates Viral envelope contains glycoproteins in the form of projections on the envelope Neuraminidase and hemagglutinin They are virus coded

25 Viral Envelope The viral envelope is acquired by the virus during the final stages of replication The envelope consists of a bilayer membrane containing glycoprotein and lipid

26 CAPSID HA DNA NA ENVELOPE SPIKES

27 Viral Envelope Functions are similar to capsid in naked virions: Protects nucleic acid from damage Facilitates attachment Confers structural symmetry Confers antigenicity

28 General Morphology of the Virion Compared to most micro-organisms the virus particle is the smallest Viruses range in size from about 20 to 25nm for parvoviruses and picornaviruses to nm for poxviruses

29 General Morphology of the Virion Most plant viruses are rod-shaped whilst the bacterial viruses show a more elaborate, tailed structure

30 Virion Morphology The shapes of most animal viruses are frequently referred to in colloquial terms e.g. spheres, rods, bullet or brick-shaped. In reality they are complex structures of precise geometric symmetry

31 Virions Morphology The shape of the virus particle is determined by the arrangements of the repeating subunit that form the capsid Precise geometric symmetries are Icosahedron Helix Complex

32 Icosahedron The shape of a regular icosahedron has 20 facets each of which is an equilateral triangle The viruses have their nucleic acid packaged inside the capsid Capsid can be naked or enveloped

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34 Helical Viruses In many RNA viruses, the viral nucleic acid is closely associated with the capsid forming a coilshaped, helical structure Helical animal viruses are always surrounded by a viral envelope

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36 Complex viruses Some viruses do not fit into any of the two symmetries due to complexity of the virion They are described as complex or brick-shaped

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38 DNA VIRUSES RNA VIRUSES

39 Virion Morphology The virus can be grouped into five categories based on their morphology and nucleocapsid symmetry

40 Virion Morphology 1. Naked icosahedral viruses 2. Enveloped icosahedral viruses 3. Naked helical viruses 4. Enveloped helical viruses 5. Complex viruses

41 Reaction to chemical and physical agents Heat and cold Different viruses show variable stability to heat and cold Icosahedral naked viruses tend to be stable at 37 C losing little infectivity after several hours

42 Reaction to chemical and physical agents Enveloped viruses are much more heat-labile; rapidly dropping in titre at 37 C

43 Effect of heat and cold on viruses Viral infectivity is generally destroyed by heating at C for 30min Viruses can be preserved by storage at sub-zero temperatures Some may withstand lyophilization and can be preserved in the dry state at 4 C

44 Effect of heat and cold on viruses Enveloped viruses tend to lose infectivity after prolonged storage even at -90 C Very sensitive to freeze and thawing

45 Stabilization of viruses by salts Many viruses can be stabilized by salts in concentration of mol/l Viruses are not inactivated in the presence of salts by heating even at 50 C for 1hr Mechanisms of this protection unkown

46 Stabilization of viruses by salts MgCl 2 stabilizes Picornaviruses MgSO 4 stabilizes Myxoviruses Na 2 SO 4 stabilizes herpes viruses The stability of viruses is important in the preparation of vaccines Salts added to vaccines to stabilize preparation

47 Stabilization of viruses by salts ph Viruses are usually stable between ph values of 5 and 9. Some viruses are resistant to acidic conditions e.g. enteroviruses All viruses are destroyed by extreme alkaline conditions

48 Photodynamic inactivation and reaction Viruses can be penetrated to a varying degree by vital dyes e.g. neutral red, toludine blue and proflavine Dyes bind to nucleic acid making it susceptible to inactivation by visible light

49 Photodynamic inactivation and reaction Ultraviolet, x-ray and high-energy particles inactivate viruses Used in sterilization of plastics, benches Dose varies for different viruses

50 Ether and Detergents Ether, like other lipid solvents acts on the lipid in the viral envelope Non ionic detergents solubilize lipid constituents of viral membrane Anionic detergents solubilize viral envelopes and disrupt capsid into separate polypeptides

51 Formaldehyde Formaldehyde destroys viral infectivity by reactivity with nucleic acid Single stranded genome much more readily inactivated than doublestranded genome

52 Formaldehyde Formaldehyde has minimal adverse effect on the antigenicity of proteins Frequently used in production of inactivated viral vaccines

53 Antibiotics & antimicrobial agents Antibiotics and sulphonamides have no effect on viruses Antimicrobial agents e.g. chlorine at high concentrations are required to kill viruses Alcohols such as isopropanol and ethanol in their pure forms are relatively ineffective against certain viruses e.g. picornaviruses 50-70% ethanol more effective

54 Viroids & Prions copyright cmassengale 54

55 Viroids Small, circular RNA molecules without a protein coat Infect plants Potato famine in Ireland Resemble introns cut out of eukaryotic copyright cmassengale 55

56 Prions Prions are infectious proteins They are normal body proteins that get converted into an alternate configuration by contact with other prion proteins They have no DNA or RNA The main protein involved in human and mammalian prion diseases is called PrP copyright cmassengale 56

57 Prion Diseases Prions form insoluble deposits in the brain Causes neurons to rapidly degeneration. Mad cow disease (bovine spongiform encephalitis: BSE) is an example People in New Guinea used to suffer from kuru, which they got from eating the brains of their enemies copyright cmassengale 57

58 Typical infectious cycle of Viruses 1. Attachment 2. Penetration 3. Uncoating 4. Transcription and/or translation 5. Replication 6. Assembly 7. Release

59 Virus recognition, attachment, and entry Specific viral receptor Co-receptor Receptor-mediated endocytosis Fusion of the viral membrane at the cell surface

60 RECEPTOR ICAM-1 CD4 VIRUS polio HIV acetylcholine rabies EGF CR2/CD21 HVEM Sialic acid vaccinia Epstein- Barr herpes Influenza, reo, corona