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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
Inactivated vaccines
Live vaccines

Interferon

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.

Definition of a Virus
Obligate
Intracellular
Parasite

Virion Structure
Lipid Envelope

Nucleic Acid

Protein
Capsid
Virion
Associated
Polymerase

Spike
Projections

Virion Morphology
Simple Structure
Repetitive Structure
High Level of Redundancy

Virus Morphology

Helical

Icosahedral

Virus Replication
1 Virus attachment

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

Cytopathic Effect (cpe)


Adenovirus

Herpes virus

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

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

In vivo Disease Processes

Cell destruction

Virus-induced changes to gene


expression

Immunopathogenic disease

Acute Virus Infection


Amount of virus

Symptoms

Virus

Time

Acute Virus Infections


Localised to specific site of
body

Development of viraemia
with widespread infection of
tissues

Poliovirus

Poliovirus
Properties of the virus

Enterovirus.
Possesses a RNA
genome.
Transmitted by the
faecal oral route.
Cause of
gastrointestinal illness
and poliomyelitis.

Poliovirus Infection
Virus
Infection

Gut

Non-neuronal
tissues

Viraemia
Neuronal
tissues

Virus excretion
in the faeces

Paralysis

Incidence of Poliomyelitis
Number of cases (in thousands)

40

Poliovirus vaccines

A: Salk killed inactivated


vaccine.
B: Sabin live attenuated
vaccine

30

20

10
0
1950

1960

1970

1980

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

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

Spread of influenza virus

Respiratory Tract

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

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

Viruses and Human Tumours

Epstein Barr Virus


Burkitts Lymphoma

Human papillomavirus
Benign warts
Cervical Carcinoma

Human T-cell Leukaemia Virus (HTLV-1)


Leukaemia

Hepatitis C virus
Liver carcinoma

Virus-induced tumours
Virus
Infection

[ ]
Uninfected
Cell

Uncontrolled cell
growth and tumour
formation

Virus-induced transformation
Normal cells

Transformed cells

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.

Treatment and Prevention


of Virus Infections

Antivirals

Vaccines and immunisation

Antiviral Targets

Attachment/Entry

Nucleic acid replication

Virus protein processing

Virus maturation

Problems with Antivirals

Identification of virus-specific
target.

Generation of resistant variants.

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