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IntroductioIntroduction n to to
virusesviruses
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Lecture topics - 1Lecture topics - 1• What is a virus?
Definition Structure and replication
• Human virus infections• Treatment
Antivirals Vaccines
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Lecture topics – 2Lecture topics – 2• Immunity to viruses
Cell-mediated Humoral
• Role of Complement• Vaccination against viruses
Inactivated vaccines Live vaccines
• Interferon
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Definition of a VirusDefinition 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.
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Definition of a VirusDefinition of a Virus
Obligate
Intracellular
Parasite
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Virion StructureVirion Structure
Nucleic Acid
Spike Projections
ProteinCapsid
Lipid Envelope
VirionAssociatedPolymerase
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Virion MorphologyVirion Morphology• Simple Structure
• Repetitive Structure
• High Level of Redundancy
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Virus MorphologyVirus Morphology
Helical Icosahedral
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Virus ReplicationVirus Replication1 Virus attachment
and entry11 2 Uncoating of virion
22
3 Migration ofgenome nucleicacid to nucleus
33
4 Transcription5 Genome replication44
55
6 Translation of virusmRNAs
66
7 Virion assembly77 8 Release of newvirus particles
88
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Cytopathic Effect (cpe)Cytopathic Effect (cpe)Adenovirus Herpes virus
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Transmission of VirusesTransmission 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
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Virus Tissue TropismVirus 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
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In vivoIn vivo Disease Processes Disease Processes
• Cell destruction
• Virus-induced changes to gene expression
• Immunopathogenic disease
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Acute Virus InfectionAcute Virus InfectionA
mou
nt o
f vir
us
Time
Symptoms
Virus
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Acute Virus InfectionsAcute Virus Infections• Localised to specific site of
body
• Development of viraemia with widespread infection of tissues
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PoliovirusPoliovirus
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PoliovirusPoliovirus
• Enterovirus.• Possesses a RNA
genome.• Transmitted by the
faecal oral route.• Cause of
gastrointestinal illness and poliomyelitis.
Properties of the virus
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Poliovirus InfectionPoliovirus Infection
Gut
VirusInfection
Virus excretionin the faeces
Viraemia
Non-neuronaltissues
Neuronaltissues
Paralysis
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Incidence of PoliomyelitisIncidence of Poliomyelitis
40
30
20
10
0
1950 1960 1970 1980
Num
ber
of c
ases
(in
thou
sand
s)
A B
Poliovirus vaccinesA: Salk – killed inactivated vaccine.B: Sabin – live attenuated vaccine
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Influenza A virusInfluenza A 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
Properties of the virus
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Influenza A virus InfectionInfluenza 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
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Spread of influenza virusSpread of influenza virus
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Respiratory TractRespiratory Tract
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1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 19990
100
200
300
400
500
600
Rat
e pe
r 100
000
pop
ulat
ion
Year
Epidemic activity
Higher than expectedseasonal activity
Normal seasonal activity
Baseline activity
Weekly consultation rates for influenza and influenza-like illness: WeeklyWeekly consultation rates for influenza and influenza-like illness: WeeklyReturns Service of the Royal College of General Practitioners, 1988 to Returns Service of the Royal College of General Practitioners, 1988 to
19991999
CDR Weekly Report: 5th November 1999
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Point mutation of HA and NAgenes
ANTIGENIC DRIFT
ANTIGENIC SHIFT
Genetic Reassortment
Human H3N2
Avian H3N8
Human H2N2
Generation of Novel Influenza A VirusesGeneration of Novel Influenza A Viruses
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Viruses and Human TumoursViruses 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
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Virus-induced tumoursVirus-induced tumoursVirusInfection
UninfectedCell
?
[ ]Uncontrolled cell
growth and tumourformation
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Virus-induced transformationVirus-induced transformation
Normal cells Transformed cells
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Virus-Induced TumoursVirus-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.
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Treatment and Prevention Treatment and Prevention of Virus Infectionsof Virus Infections
• Antivirals
• Vaccines and immunisation
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Antiviral TargetsAntiviral Targets• Attachment/Entry
• Nucleic acid replication
• Virus protein processing
• Virus maturation
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Problems with AntiviralsProblems with Antivirals
• Identification of virus-specific target.
• Generation of resistant variants.