Introduction

to
viruses

What are Viruses

A virus is a non-cellular particle made up of
genetic material and protein that can invade
living cells.

 Viruses

are composed
of a core of nucleic
acid
The Nucleic acid core
is surrounded by a
protein coat called a
capsid
The Nucleic core is
either made up of
DNA or RNA but
never both

The Structure Of a Virus

 Change

DNA
into RNA.
Example of a
Retrovirus is
HIV

Retrovirus

A typical, "minimal"
retrovirus consists of:
an outer envelope which
was derived from the
plasma membrane of its
host
many copies of an
envelope protein
embedded in the lipid
bilayer of its envelope
a capsid; a protein shell
containing
two molecules of RNA
and
molecules of the
enzyme reverse
transcriptase

WHATISAVIRUS?
Virusesmaybedefinedasacellular
organismswhosegenomesconsistof
nucleicacid,andwhichobligatelyreplicate
insidehostcellsusinghostmetabolic
machinerytodifferentextents,toforma
poolofcomponentswhichassembleinto
particlescalledvirions.
Virusescannotbe
grownonsterile
media,butrequire
thepresenceof
specifichostcells.
Avirusdiffersfromacellinthreefundamentalways:
i
Avirususuallyhasonlyasingletypeofnucleicacid
servingasitsgeneticmaterial.Thiscanbesingleordouble
strandedDNAorRNA;
ii Virusescontainnoenzymesofenergymetabolism,thus
cannotmakeATP;
iii Virusesdonotencodesufficientenzymaticmachineryto
synthesizetheircomponentmacromolecules,specifically,no
proteinsynthesismachinery.

Fundamentally then, a virus

is:
A package of genetic information
protected by a protein shell for
delivery into a host cell to be
expressed and replicated

Virusesaredistinguishedfromotherobligateparasites,
someofwhichareevensimplerthanviruses:
MYCOPLASMA:Smallbacteriumthatgrowsonlyincomplexmediumorattachedto
eucaryoticcells.
CHLAMYDIA:Obligateintracellularbacterialparasitewhichdependsoneucaryotic
cellforenergy.
PROTOZOA:Obligateintracellularparasitethatreplicatewithineucaryoticcells.
VIROID:Infectiousagentsofplantsthatexistasnakednucleicacid(circularsingle
stranded(ss)ssRNA).
HEPATITISDELTAVIRUS(HDV):Viroidlikeagentwhosereplicationis
dependentuponHBV.

Viraldiseaseshaveplayedamajorroleinhumanhistoryover
whatevertimescalewechoosetoexplore:
Overthepast1000years:SmallpoxandmeasleswerebroughttoNorth
andSouthAmericabyearlyEuropeanexplorers/conquerers.These
diseases,forwhichthenativeAmericanpopulationshadnoacquired
partialimmunity,killedlargefractionsofthepopulations,andwerea
majorfactorinthedecimationofthesesocieties.
Overthepast100years:Anewlyemerged
strainofinfluenzakilled20millionpeoplein
19181919intheimmediateaftermathofWorld
WarI.Adecadelater,poliobecameoneofthe
mostfearedinfectionsofchildrenandyoung
adults(includingFranklinD.Roosevelt,theU.S.
PresidentthroughouttheDepressionandWorld
WarII).
Asthecenturyentereditsfinal20years,anew
~100%lethalvirus,HIV,spreadrapidlyaround
theworldviabodyfluidtransmission.

Overthepast10years:AstheglobalHIVepidemiccontinues,sporadic
casesandoutbreaksinhumansofsomenonhumanhostvirusessuchas
EbolaandHantaraisetheconcernaboutfutureepidemicsbyotherviruses
inthenewcentury.

FourCornersVirus
(Hanta)

PREVENTINGCONTROLINGCURINGVIRALDISEASES
Smallpox:effectivevaccine;thisistheonlyviraldiseasethathasbeenwipedout
worldwide
Measles:effectivevaccinesince1963;thisdiseasecouldbeeliminatedwithaworld
wideeffort
Influenza:effectivestrainspecificvaccine,butnewvariantstrainsemerge
periodically
Polio:effectivevaccine;willsoonbethesecondviraldiseasewipedout
HIV:novaccine;effectivedrugs,buttheyarecostlyandtoxic,plusresistantstrains
appear.Worldwidespreadcontinuesviaintimatecontact.50millioninfectedthusfar
Ebola:novaccine;importanthostspeciesunknown(foundrecentlyinchimpsand
rodents);outbreakscontrollablebecausepeoplediequicklyandhumanhuman
transmissionisviablood
Hanta:novaccine;rodenthost;easytransmissiontohumans,butoutbreaks
controllable

Howarevirusesclassified?
Hierarchicalvirusclassification:(order)familysubfamilygenusspecies
strain/type
Allfamilieshavethesuffixviridae,e.g.:
*
*
*
*

Poxviridae
Herpesviridae
Parvoviridae
Retroviridae

Generahavethesuffixvirus.WithinthePicornaviridaethereare5genera:
*
*
*
*
*

enterovirus(alimentarytract),speciese.g.poliovirus1,2,3
cardiovirus(neurotropic),speciese.g.mengovirus
rhinovirus(nasopharyngealregion),speciese.g.Rhinovirus1a
apthovirus(clovenfootedanimals),speciese.g.FMDVC
hepatovirus(liver),speciese.g.HepatitisAvirus

Virusnamingandclassification

Usuallybasedondataavailableatthetimeof
discovery:
i

Diseasetheyareassociatedwith,e.g.:
Poxvirus,Hepatitisvirus,HIV,measlesvirus

ii

Cytopathologytheycause,e.g.:
RespiratorySyncytialvirus,Cytomegalovirus

iii

Siteofisolation,e.g.:
Adenovirus,Enterovirus,Rhinovirus

iv

Placesdiscoveredorpeoplethat
discoveredthem,e.g.:
EpsteinBarrvirus,RiftValleyFever

Biochemicalfeatures,e.g.:
Retrovirus,Picornavirus,Hepadnavirus

RSV

Thesenamingconventionscanleadtoconfusion
later,e.g.,
viralhepatitisiscausedbyatleast6different
viruses
Enterically
Infectious
A
E transmitted

Viral
hepatitis
Serum

F, G,
? Other *

NANB

B
D

Parenterally
transmitted

*1020%ofcasesofpresumedviralhepatitisarestillnot
accountedfor

Thus,
Different viruses can cause (nearly)
the same symptoms. e.g., the
hepatitis viruses
However, different members of the
same group can cause different
symptoms. e.g., the herpes viruses

Herpesviruses

HSV

Herpes Simplex Virus

VZV
CMV
EBV

Varicella Zoster Virus

Cytomegalovirus
Epstein-Barr Virus

carcinoma
and HHV-6, HHV-7, HHV-8..
(Human HerpesVirus-#)

Cold sores (type 1),

Genital lesions (type 2)
Chicken pox
Mononucleosis
Mononucleosis,
Burkitts lymphoma,
Nasopharyngeal

VirusClassificationisnowbasedprincipallyonanalysisofthe
particle:
Morphology:
byelectronmicroscopy
Serology:
antigeniccrossreactivity
Geneticmaterial:
formofnucleicacid
ssDNA(+orstrand)
dsDNA
ssRNA(+orstrand)
dsRNA
segmentedRNA
geneticorganization
sequencehomology
DNAsequence
Hybridization

Rotavirus

Animalvirusclassification:DNAViruses
Family

Pox

Herpes

Genome

<dsDNA>

Capsid
symmetry

Complex

Papova

Parvo

Hepadna

ssDNA

PartialdsDNA

<Icosahedral>

Envelope

<Yes>

e.g.

Vacciniavirus

Molluscum
Contagiosum

Adeno

Herpessimplex
virus2

<No>
Human
adenovirus

Papilloma

Adeno
Associated

Yes
HepatitisB

PlusSenseRNAViruses

MinusSenseRNAViruses

 The

tiniest viruses
are 20 nm in
diameter. (smaller
than a ribosome)

They

consist of
nucleic acids
enclosed in a protein
coat and sometimes
a membranous
envelop.

The

genomes (sets of genes) maybe

Double stranded DNA

Single stranded DNA
Double stranded RNA
Single stranded RNA

They

are called either a DNA or RNA

virus depending on the type of
nucleotide in the make-up.
They may be linear or circular
The smallest have only 4 genes and
largest have several hundred.

Capsid

a protein shell that covers the

viral genome. They may be
Rod-shaped
Polyhedral
More complex

Capsids are built from large numbers of

protein subunits called CAPSOMERES
The most complex capsids are found in
viruses that infect bacteria
BACTERIOPHAGES (T1-T7)
They have a protein tail piece with tail fibers
that attach to the bacterium

Virus structure, classification and

replication

Structures compared

From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-4.

DNA
or
RNA

Capsid
protein

Nucleocapsid

Nucleocapsid

Lipid membrane,
glycoproteins

Basic virus structure

Naked
capsid virus

Enveloped virus

Capsid symmetry
Icosahedral

Helical
Naked capsid

Enveloped

Matrix
Lipid
Glycoprotein

 Envelope is sensitive to
Drying
Heat
Detergents
Acid
Consequences
Must stay wet during transmission
Transmission in large droplets and secretions
Cannot survive in the gastrointestinal tract
Do not need to kill cells in order to spread
May require both a humoral and a cellular immune
response

Properties of enveloped viruses

Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA Box 6-5

Capsid is resistant to

Drying
Heat
Detergents
Acids
Proteases

Can survive in the gastrointestinal tract

Retain infectivity on drying
Survive well on environmental surfaces
Spread easily via fomites
Must kill host cells for release of mature virus particles
Humoral antibody response may be sufficient to neutralize
infection

Consequences

Properties of naked capsid viruses

Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4

 Structure

Nucleic acid in a protein shell, +/- lipid envelope

Structure impacts on biological properties
Classification

Many virus families, organized by structure and biology

Replication

Generic scheme
Varying strategies depending on nucleic acid

Summary: structure,
classification & replication

Reproduction
Viruses

are obligate
intracellular parasites
that can reproduce
only within a host cell.
They do not have
Enzymes for metabolism
Do not have ribosomes
Do not have the
equipment to make
proteins

Some

not.

are broad based while others are

Swine flu virus can infect swine or humans

Rabies can infect may mammals
Some

can parasitize only E. coli

Eukaryote viruses are usually tissue
specific
Viruses use a lock and key fit to identify
hosts.
Each type of virus can infect and parasitize only a
limited range of host cells called its HOST RANGE.

Reproduction occurs using lytic

or lysogenic cycles
The Lytic Cycle
Culminates in the death
of the host cell
Virulent viruses
reproduce only by lytic
cyle.
Natural selection favors
bacterial mutations with
receptor sites that are
resistant to a particular
phage or that have
restriction enzymes to
destroy the phages.

The

Lysogenic Cycle

Replication of the viral

genome without
destroying the host
cell.
A temperate virus may
reproduce by either
cycle.
Lambda virus:
resembles T4 but only
has a single short tail
fiber

RETROVIRUSES
Most complicated
Genetic information
flows in the reverse
direction
Have the enzyme
reverse transcriptase

Transcribes DNA from an

RNA template

The newly made DNA

than integrates as a
provirus into the
nucleus of the animal
cell
The hosts RNA
polymerase transcribes
the virual DNA into RNA
molecules.

Viral Diseases
The

damage caused by a viral disease

depends on the ability of the tissue infected
to regenerate by cell division.
Cold virus we recover from
Poliovirus - attacks

Vaccines

are harmless variants of pathogenic

microbes that stimulate the immune system
to defenses against the pathogen.

 The

link between viral infection and the

symptoms it produces is often obscure.
Some viruses damage or kill cells by triggering
the release of hydrolytic enzymes from lysosomes.
Some viruses cause the infected cell to produce
toxins that lead to disease symptoms.
Other have molecular components, such as
envelope proteins, that are toxic.

In

some cases, viral damage is easily

repaired (respiratory epithelium after a cold),
but in others, infection causes permanent
damage (nerve cells after polio).

 The

first vaccine was developed in the late

1700s by Edward Jenner to fight smallpox.

Jenner learned from his patients that milkmaids

who had contracted cowpox, a milder disease that
usually infects cows, were resistant to smallpox.
In his famous experiment in 1796, Jenner
infected a farmboy with cowpox, acquired from
the sore of a milkmaid with the disease.
When exposed to smallpox, the boy resisted the
disease.
Because of their similarities, vaccination with the
cowpox virus sensitizes the immune system to
react vigorously if exposed to actual smallpox
virus.

Effective

vaccines against many other

viruses exist.

 Vaccines

can help prevent viral infections,

but they can do little to cure most viral
infection once they occur.
Antibiotics which can kill bacteria by
inhibiting enzyme or processes specific to
bacteria are powerless again viruses, which
have few or no enzymes of their own.
Some recently-developed drugs do combat
some viruses, mostly by interfering with viral
nucleic acid synthesis.
AZT interferes with reverse transcriptase of HIV.
Acyclovir inhibits herpes virus DNA synthesis.

 In

recent years, several very dangerous

emergent viruses have risen to
prominence.
HIV, the AIDS virus, seemed to appear suddenly
in the early 1980s.
Each year new strains of influenza virus cause
millions to miss work or class, and deaths are not
uncommon.
The deadly Ebola
virus has caused
hemorrhagic fevers
in central Africa
periodically since
1976.
Fig.18.8a

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

Acute Virus Infections

Localised

body

to specific site of

Development

of viraemia
with widespread infection
of tissues

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

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

Epstein

Barr Virus

Burkitts Lymphoma
Human

papillomavirus

Benign warts
Cervical Carcinoma
Human

T-cell Leukaemia Virus (HTLV-1)

Leukaemia
Hepatitis

C virus

Liver carcinoma

Viruses and Human

Tumours

Virus-induced tumours
Virus
Infection

[ ]
Uninfected
Cell

Uncontrolled cell
growth and tumour
formation

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.

Source of infection:

Shedding virus

susceptible

Man > 99%

animals

zoonosis

Routes of entry:
Inhalation
ingestion
inoculation
sexual

Blood
organ t/plant
Congenital / vertical

vertical transmission
Some

viruses can cross

the placenta
Infection during
pregnancy can damage
the foetus

e.g. Rubella, Cytomegalovirus

Rubella:
Infection during first trimester:
Congenital infection syndrome:
cataracts
heart defects
micro-cephaly
mental retardation
deafness

Disease determined by cell tropism:

localised

disseminated

After entry into the body:

Viral

infections can be localised, to the site

of inoculation
e.g.
Human papillomaviruses - skin (warts)

or the body surface

e.g. Rotavirus
Infantile gastro-enteritis

Respiratory tract
e.g. Influenza

Virus replicates and is shed from the body surface, highly infectious

Dissemination.
occurs via the blood
(viraemia) or lymphatic
system
viruses may travel free in
the plasma but usually hitch
a ride with monocytes or
lymphocytes
a few viruses can spread via
the nervous system eg.
rabies

Some examples of generalised viral infections:

Measles

Viral haemorrhagic fever

zoonosis

Rabies

Motor neurone

How do viruses cause disease?

1.

2.
3.

by damaging/killing cells outright

by inducing immuno-pathology
by transforming cells

cancer

. by damaging/killing cells
e.g.Poliomyelitis
the virus is cytolytic
destroys motor neurons in the spinal cord,
and so causes paralysis

X-section of the spinal cord

showing severe inflammation
of anterior horn cells

. by inducing immunopathology
The patients T cells attack and destroy virus-infected cells
Inflammation and cell death
Help!

Tc

ell

by transforming cells
cancer
When

a virus infects a cell, it expresses proteins

that cause the cell to proloferate and/or block
apoptosis

Cancer

is multi-factorial: Oncogenic viruses are

very common, only a small % of people infected
actually get cancer

Major viral cancers

Viruses are involved in about 15% of human cancers:

Cancer of the cervix

Cancer of the liver
Certain leukaemias & lymphomas
Kaposis sarcoma

Copyright John Valentine DMD 1999

B Latency:
++++++++++

Primary infection
e.g. herpes simplex virus

+++

reactivation

Classification of Human Viruses

Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Table 2.1

Major diseases caused by human viruses