IntroductioIntroduction n to to

virusesviruses

Lecture topics - 1Lecture topics - 1• What is a virus?

Definition Structure and replication

• Human virus infections• Treatment

Antivirals Vaccines

Lecture topics – 2Lecture topics – 2• Immunity to viruses

Cell-mediated Humoral

• Role of Complement• Vaccination against viruses

Inactivated vaccines Live vaccines

• Interferon

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.

Definition of a VirusDefinition of a Virus

Obligate

Intracellular

Parasite

Virion StructureVirion Structure

Nucleic Acid

Spike Projections

ProteinCapsid

Lipid Envelope

VirionAssociatedPolymerase

Virion MorphologyVirion Morphology• Simple Structure

• Repetitive Structure

• High Level of Redundancy

Virus MorphologyVirus Morphology

Helical Icosahedral

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

Cytopathic Effect (cpe)Cytopathic Effect (cpe)Adenovirus Herpes virus

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

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

In vivoIn vivo Disease Processes Disease Processes

• Cell destruction

• Virus-induced changes to gene expression

• Immunopathogenic disease

Acute Virus InfectionAcute Virus InfectionA

mou

nt o

f vir

us

Time

Symptoms

Virus

Acute Virus InfectionsAcute Virus Infections• Localised to specific site of

body

• Development of viraemia with widespread infection of tissues

PoliovirusPoliovirus

PoliovirusPoliovirus

• Enterovirus.• Possesses a RNA

genome.• Transmitted by the

faecal oral route.• Cause of

gastrointestinal illness and poliomyelitis.

Properties of the virus

Poliovirus InfectionPoliovirus Infection

Gut

VirusInfection

Virus excretionin the faeces

Viraemia

Non-neuronaltissues

Neuronaltissues

Paralysis

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

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

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

Spread of influenza virusSpread of influenza virus

Respiratory TractRespiratory Tract

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

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

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

Virus-induced tumoursVirus-induced tumoursVirusInfection

UninfectedCell

?

[ ]Uncontrolled cell

growth and tumourformation

Virus-induced transformationVirus-induced transformation

Normal cells Transformed cells

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.

Treatment and Prevention Treatment and Prevention of Virus Infectionsof Virus Infections

• Antivirals

• Vaccines and immunisation

Antiviral TargetsAntiviral Targets• Attachment/Entry

• Nucleic acid replication

• Virus protein processing

• Virus maturation

Problems with AntiviralsProblems with Antivirals

• Identification of virus-specific target.

• Generation of resistant variants.