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
Spike
Polymerase
Projections
 Virion Morphology
• Simple Structure
• Repetitive Structure
• High Level of
Redundancy
Virus Morphology

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

8
 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
Symptoms
Amount of virus

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
Non-neuronal
tissues

Gut Viraemia
Neuronal
tissues

Virus excretion
in the faeces Paralysis
Incidence of Poliomyelitis
A B

40
Poliovirus vaccines
Number of cases (in thousands)

30 A: Salk – killed inactivated

vaccine.
B: Sabin – live attenuated
20 vaccine

10

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

600
Rate per 100 000 population

500
Epidemic activity

400
Higher than expected Baseline activity
300 seasonal activity

200
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 Human H3N2

Genetic Reassortment

Avian H3N8
Point mutation of HA and NA
genes

ANTIGENIC DRIFT
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
Virus-induced tumours
Virus
Infection

[ ]
Uninfected Uncontrolled cell
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.