Viruses are very small particles which

infect humans, animals, plants and even

bacteria.

Obligate intracellular parasites.

Viruses range in size from 20-400nm.Are viruses living organisms?

NO! They can only replicate in living cells ,

employ host cell’s replicative and metabolic

pathways.

Outside cells they are essentially inert

macromolecules (Protein & NA).

Obligate intracellular

parasites

EssentiEssentialal

Core of genetic material(nucleic acid):

Single or double strands DNA or RNA, linear or

circular, one piece or segmented.

Protein coat or capsid:

Composed of a large number of subunits

(capsomeres).

Protects viral genes from inactivation by

adverse environmental factors, help

attachment to specific receptors on host cells.

Core + capsid = nucleocapsid

Envelope:

Lipid or lipoprotein bilayer, not present in all

virus species, derived at least partially from

host cell membrane , contain viral

glycoprotein

• Structural

• Functional

Enzymes:

Found only in very few number of viruses.

Virion Virion

• Complete virus particle : nucleic acid +

protein coat, which may be surrounded by an

envelope.

• It is the form in which the virus moves between

cells or hosts.

Viral Structure - Viral Structure - OverviewOverview

Fig 1. Schematic overview of the structure of animal viruses

** does not exist in all viruses

Nucleic acid

CapsidNucleocapsid

Envelope protein

Membrane proteinViral envelope**

Spike protein

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The nucleocapsid which may have

Icosahedral: (Cubic) Has 20 faces, each an

equilateral triangle (e.g. adenoviruses).

Helical: Protein binds around DNA/RNA in a

helical fashion (e.g. Influenza virus).

Complex: no specific symmetry

(e.g. Bacteriophage , Poxviruses)

Icosahedral Helical Complex

The host cell act as a factory

providing substrates, energy, and

machinery for synthesis of coat

proteins , nucleic acid genomes.

Recognition and attachment to the

target cell:

It depends on legends “ Surface protein

” of the virus and receptors in the host

cell.

HIV binds to CD4 receptors in cells of

immune system.

EBV binds to CD21 receptors on B cells.

Poliovirus attach only to cells in CNS and

GIT.

Attachment step initiate irreversible

structural changes in the virion.

Attachment step is temperature dependent.

Penetration or engulfment:

• Non enveloped “Naked” viruses penetrate

by

Receptor mediated endocytosis.

Translocation of the virion across the host cell

membrane.

• Enveloped viruses penetrate cells through

Fusion of viral envelope with host cell membrane.

May or may not involve receptor mediated

endocytosis.

Uncoating:

Enveloped viruses are usually uncoated upon

fusion to the cell membrane.

The virus then delivered to the replication

site.

• DNA viruses replicates in the nucleus

except poxvirus.

• RNA viruses replicates in the cytoplasm

except retroviruses (HIV).

Expression of viral genomes and

synthesis of viral components:

It is the most important step in virus

replication.

It depends on the formation of functional

mRNA capable of binding to the ribosome

and being translated into proteins.

DNA viruses that replicates in the nucleus

utilize the cell’s DNA dependent RNA

polymerase.

While poxvirus which replicates in the

cytoplasm must encode for such enzyme.

RNA viruses must encodes for enzymes

which transcript the RNA.

Protein synthesis takes place in two stages:

Early stage: synthesis of proteins that

inhibit the cell metabolism and enzymes

(polymerases) necessary for nucleic acid

replication.

Late stage: synthesis of protein capsids.

Replication differs according to the type of

the nucleic acid core.

Assembly:

Association of cores and coats.

Usually starts as soon as necessary pieces

are synthesized.

It looks like a box of capsomeres enclosing

the genome.

Release:

Naked viruses are released after lyses of the

cell while enveloped viruses are released

usually by budding.

Time course of Time course of replicationreplication

The time interval after penetration and

before assembly is called eclipse cycle.

During the eclipse cycle infective virion

couldn’t be isolated.

Structure: DNA or RNA (most satisfactory for

microbiologists).

Morphology: icosahedral, helical or complex,

also enveloped or non, and others, picorna virus

(small), togavirus (cloak), coronavirus (crown),

rhabdovirus (rod).

Disease: hepatitis virus, encephalitis virus,

influenza virus (most satisfactory for medicine).

Tissue (tropism): adenovirus (glands),

enterovirus (intestine) or myxovirus (mucous).

Viruses grow only in living cells which may be:

I) Tissue culture: I) Tissue culture:

Animal or human tissue culture pieces treated

with trypsin to separate the cell.

They are grown in presence of growth medium

containing serum.

A monolayer or sheet of cells is formed on the

flat surface of the container (glass or plastic

bottle or tube).

There are three types of tissue cultures:

a) Primary cell lines: fragments of tissue e.g.

monkey kidney. They can only divide for 4-6

subcultures, then degenerate.

b) human diploid cell lines: Usually fibroblasts

from human embryo tissue. They grow rapidly

and can be subcultured 50 times.

c) Continuous cell lines: are derived from tumor

cells and can be subcultured indefinitely e.g. Hella

cells derived from the carcinoma of the cervix.

II) Chick or duck embryo:II) Chick or duck embryo:

The virus is allowed to grow in one of the

following cavities within the fertilized egg.

a) Embryo e.g. yellow fever virus.

b) Allantoic or Amniotic cavity: e.g. influenza virus.

c)Chorioallantoic membrane: e.g. pox and herpes

viruses.

III) Intact animal: III) Intact animal:

The white suckling mouse is widely used for

encephalitis viruses, calves are used for pox

virus.

Cultivation in animals has the disadvantage of

easy transmission of infection.

Rarely used now.

1. Cytopathogenic or cytopathic effect (CPE):

Characteristic changes due to permanent or

temporary cell damage as cell death

(poliovirus), cluster formation (adenovirus),

giant cell formation (measles and mumps

viruses) or cell transformation (tumor viruses).

2. Inclusion bodies:

Observed by light microscope.

They are aggregates or just sites of replication

of the virus.

e.g.

Cytoplasmic Negri bodies in brain cells of

rabies infected animal, cytoplasmic Guarnieri's

bodies of poxvirus.

Nuclear bodies of adenovirus.

Nuclear and cytoplasmic bodies in case of

cytomegalovirus.

3. Haemadsorption:

Viruses which contain haemagglutinin spikes

e.g. influenza virus are able to form clumps of

RBCs if added to the tissue culture.

4. Interference:

Host cells infected with a virus may acquire

resistance to infection by a second virus, of the

same type or another one (it is not common to

all viruses e.g. not found between mumps,

measles and rubella).

Some viruses do not produce CPE, however, their

growth can be proved by their ability to interfere with

another CPE producing virus e.g. rubella and ECHO

(Enteric Cytopathic Human Orphan) virus.

5. Fluorescent antibody staining.

6. Detection of viral antigens by serology.

7. Acid production:

Normal cells produce acids, thus:

• Normal tissues + Phenol red Yellow (acid color).

• Infected tissues + Phenol red Red (alkaline color).

A. Local infections:

1. Skin: e.g. warts caused by papillomavirus.

2. Respiratory tract infections affecting the

mucous membranes e.g. influenza and

common cold.

3. Alimentary tract e.g. more than 60% of

diarrhea in infants is caused by rotavirus.

Local infections are characterized by short

incubation period and short lasting

immunity.

B. Systemic infection:

The virus passes through lymphatics, blood,

tissues or nerves, reaching the target tissue

(tropism), e.g. hepatitis, measles,

poliomyelitis.

Administration of neutralizing antibodies

before the viraemic phase could prevent the

development of the disease.

Systemic infections are characterized by long

incubation period and long lasting immunity.

C. Persistent infection: Due to escape of the virus from the host

defense mechanism. It is either1. Latent infection: the virus remain hidden

most of the time with intermittent reactivation and development of the disease e.g. herpes simplex and adeno infections. The virus is not detected during latency.

2. Chronic infection: the virus usually has long incubation period and is always shedding i.e. can be detected all the time, during symptoms and in absence of symptoms, e.g. hepatitis B.

3. Slow infection: are viruses with long

incubation period and slow multiplication

e.g. subacute sclerosing panencephalitis

caused by a variant of measles virus.

4. Congenital or teratogenic infection:

many viruses penetrate the placenta during

pregnancy causing congenital defect in the

embryo, e.g. rubella, cytomegalo, hepatitis

viruses and HIV.

5. Oncogenicity (tumor causing): resulting in transformation of infected cells.

Viral genes become integrated into host cell chromosome e.g. of DNA viruses (herpes simplex type 2 virus, Epestein Barr virus, hepatitis B&C viruses and papovirus) e.g. of RNA viruses is the retrovirus group {human T lymphotropic viruses 1&2 (HTLV 1&2)} c.f. HIV formerly known as HTLV 3 which is non oncogenic.

With RNA tumor viruses, viral RNA acts as a template for synthesis of viral DNA- through the action of reverse transcriptase. The DNA copy of the viral RNA is integrated into the host cell chromosome.