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Introduction to viruses

Introduction to viruses. Lecture topics - 1. What is a virus? Definition Structure and replication Human virus infections Treatment Antivirals Vaccines. Lecture topics – 2. Immunity to viruses Cell-mediated Humoral Role of Complement Vaccination against viruses

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Introduction to viruses

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  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. Lipid Envelope Nucleic Acid Protein Capsid Virion Associated Polymerase Spike Projections Virion Structure

  7. Virion Morphology • Simple Structure • Repetitive Structure • High Level of Redundancy

  8. Helical Icosahedral Virus Morphology

  9. 1 Virus attachment and entry 1 2 Uncoating of virion 3 Migration of genome nucleic 5 acid to nucleus 4 Transcription 4 2 5 Genome replication 6 Translation of virus 3 mRNAs 7 Virion assembly 7 8 Release of new virus particles 6 8 Virus Replication

  10. Adenovirus Herpes virus Cytopathic Effect (cpe)

  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. Symptoms Amount of virus Time Virus Acute Virus Infection

  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. Virus Infection Viraemia Gut Neuronal tissues Virus excretion in the faeces Paralysis Poliovirus Infection Non-neuronal tissues

  19. A B 40 30 20 Number of cases (in thousands) 10 0 1950 1960 1970 1980 Incidence of Poliomyelitis Poliovirus vaccines A: Salk – killed inactivated vaccine. B: Sabin – live attenuated vaccine

  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. 600 500 400 300 200 100 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Weekly consultation rates for influenza and influenza-like illness: Weekly Returns Service of the Royal College of General Practitioners, 1988 to 1999 Epidemic activity Higher than expected seasonal activity Baseline activity Rate per 100 000 population Normal seasonal activity Year CDR Weekly Report: 5th November 1999

  25. Human H2N2 Human H3N2 Genetic Reassortment Avian H3N8 Point mutation of HA and NA genes Generation of Novel Influenza A Viruses ANTIGENIC SHIFT ANTIGENIC DRIFT

  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 Infection [ ] Uncontrolled cell growth and tumour formation Uninfected Cell ? Virus-induced tumours

  28. Normal cells Transformed cells Virus-induced transformation

  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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