lecture 55

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I

NTRODUCTION TO VIRUSES

DR NAZIA KHAN

ASSISTANT PROFESSOR

COLLEGE OF MEDICINE

2.

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4.

1.

5.

Describe a virus. How is a virus different from viroid and prion

Define components of a virus

Discuss the classification of virus

Discuss briefly the effect of physical and chemical agents on virus with clinical correlation

Give an overview of replication cycle of virus and its clinical implication

• Viruses are the smallest infectious agents (20 nm to about 300 nm in diameter)

• contain only one kind of nucleic acid (RNA or

DNA) as their genome never both

• The nucleic acid is encased in a protein shell, which may be surrounded by a lipid-containing membrane.

• obligate intracellular parasites.

• cause large number of diseases such as common cold to rabies ,AIDS

• The entire infectious unit is termed a virion.

• Viruses are inert in the extracellular environment; they replicate only in living cells, being parasites at the genetic level.

A

RE VIRUSES BACTERIA

VIROIDS AND PRIONS

THE SAME

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VIROIDS

Small infectious agents that cause diseases of plants.

Viroids are agents that do not fit the definition of classic viruses.

Viroids replicate by an entirely novel mechanism. viroids have been detected only in plants; none have been demonstrated to exist in animals or humans.

PRIONS

Infectious particles composed solely of protein with no detectable nucleic acid.

Highly resistant to inactivation by heat, formaldehyde, and ultraviolet light that inactivate viruses.

The prion protein is encoded by a single cellular gene.

Prion diseases, called "transmissible spongiform encephalopathies," include scrapie in sheep, mad cow disease in cattle, and kuru and Creutzfeldt-Jakob disease in humans.

Prions do not appear to be viruses

C

OMPONENTS OF A VIRUS

 Capsid : eht sesolcne taht ,taoc ro ,llehs nietorp ehT

.

emoneg dica cielcun

 Capsomere :

Morphologic units seen in the electron microscope on the surface of icosahedral virus particles

 Defective virus : yllanoitcnuf si taht elcitrap suriv A

.

noitacilper fo tcepsa emos ni tneicifed

 Envelope : A lipid-containing membrane that surrounds some virus particles

 Nucleocapsid : The protein-nucleic acid complex representing the packaged form of the viral genome .

 Structural units : fo skcolb gnidliub nietorp cisab ehT

naht erom fo noitcelloc a yllausu era yehT .taoc eht

si tinu larutcurts ehT .tinubus nietorp lacitnedinon eno

a sa ot derrefer netfo protomer .

 Subunit : .

niahc editpepylop lariv dedlof elgnis A

 Virion : secnatsni emos nI .elcitrap suriv etelpmoc ehT

si noiriv eht ,)sesurivanrocip ,sesurivamollipap ,ge(

xelpmoc erom nI .dispacoelcun eht htiw lacitnedi

siht ,)sesurivoxymohtro ,sesurivsepreh( snoiriv

gnidnuorrus a sulp dispacoelcun eht sedulcni

refsnart ot sevres ,noiriv eht ,erutcurts sihT .epolevne

.

rehtona ot llec eno morf dica cielcun lariv eht

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2.

C LASSIFICATION OF VIRUSES : BASED ON …….

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Virion morphology, including size, shape, type of symmetry, presence or absence of peplomers, and presence or absence of membranes.

2.

3.

Virus genome properties, including type of nucleic acid

(DNA or RNA), size of genome in kilobases (kb) or kilobase pairs (kbp), strandedness

(single or double), whether linear or circular, sense

(positive, negative, ambisense), segments (number, size), nucleotide sequence,

Physicochemical properties

of the virion, including molecular mass, buoyant density, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents

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7.

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Virus protein properties, including number, size, and functional activities of structural and nonstructural proteins, amino acid sequence, modifications , and special functional activities

(transcriptase, reverse transcriptase, neuraminidase, fusion activities).

Genome organization and replication, including gene order, number and position of open reading frames, strategy of replication (patterns of transcription, translation), and cellular sites

(accumulation of proteins, virion assembly, virion release).

Antigenic properties.

Biologic properties, including natural host range, mode of transmission, vector relationships, pathogenicity, tissue tropisms, and pathology.

E FFECT OF PHYSICAL AND CHEMICAL AGENTS ON VIRUS

1.

Heat & Cold:

Icosahedral viruses tend to be stable, losing little infectivity after several hours at 37°C

Enveloped viruses are much more heat-labile, rapidly dropping in titer at 37 °C.

Viral infectivity is generally destroyed by heating at 50–60 °C for 30 minutes,

Viruses can be preserved by storage at subfreezing temperatures, and some may withstand lyophilization and can thus be preserved in the dry state at 4 °C or even at room temperature.

Viruses that withstand lyophilization are more heat-resistant when heated in the dry state.

Enveloped viruses tend to lose infectivity after prolonged storage even at -90 °C and are particularly sensitive to repeated freezing and thawing.

2.

Stabilization of Viruses by Salts:

Many viruses can be stabilized by salts like MgCl

2

The stability of viruses is important in the preparation of vaccines.

The ordinary nonstabilized oral poliovaccine must be stored at freezing temperatures to preserve its potency. However, with the addition of salts for stabilization of the virus, potency can be maintained for weeks at ambient temperatures even in the high temperatures of the tropics.

3.

pH:

Viruses are usually stable between pH values of 5.0 and 9.0. Some viruses (eg, enteroviruses) are resistant to acidic conditions. All viruses are destroyed by alkaline conditions.

4.

Radiation :

Ultraviolet, x-ray, and high-energy particles inactivate viruses. Infectivity is the most radiosensitive property because replication requires expression of the entire genetic contents. Irradiated particles that are unable to replicate may still be able to express some specific functions in host cells.

5.

Photodynamic Inactivation

Viruses are penetrable to a varying degree by vital dyes such as toluidine blue, neutral red, and proflavine. These dyes bind to the viral nucleic acid, and the virus then becomes susceptible to inactivation by visible light.

6.

Ether Susceptibility

Ether susceptibility can be used to distinguish viruses that possess an envelope from those that do not

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Detergents : Nonionic solubilize lipid constituents of viral membranes. Anionic detergents solubilize viral envelopes; in addition, they disrupt capsids into separated polypeptides.

Formaldehyde : Formaldehyde destroys viral infectivity by reacting with nucleic acid.

Viruses with single-stranded genomes are inactivated much more readily than those with double-stranded genomes. Formaldehyde has minimal adverse effects on the antigenicity of proteins and therefore has been used frequently in the production of inactivated viral vaccines.

Antibiotics & Other Antibacterial Agents : Antibacterial antibiotics and sulfonamides have no effect on viruses.

R

EPLICATION OF

V

IRUSES

Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery

In order for a virus to replicate, viral proteins must be synthesized by the host cell protein-synthesizing machinery. Therefore, the virus genome must be able to produce a usable mRNA.

The unique feature of viral multiplication is that, soon after interaction with a host cell, the infecting virion is disrupted and its measurable infectivity is lost.

After the synthesis of viral nucleic acid and viral proteins, the components assemble to form new infectious virions. The duration of the virus replication cycle also varies widely, from 6–8 hours (picornaviruses) to more than 40 hours (some herpesviruses).

G ENERAL S TEPS IN V IRAL R EPLICATION C YCLES

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Attachment, and Uncoating interaction of a virion with a specific receptor site on the surface of a cell.

Receptor molecules differ for different viruses but are generally glycoproteins

Ex: HIV binds to the CD4 receptor on cells of the immune system

Penetration

The virus particle is taken up inside the cell. This step is referred to as penetration or engulfment. In some systems, this is accomplished by receptormediated endocytosis, with uptake of the ingested virus particles within endosomes.

Uncoating : occurs concomitantly with or shortly after penetration. Uncoating is the physical separation of the viral nucleic acid from the outer structural components of the virion so that it can function

Expression of Viral Genomes and Synthesis of

Viral Components : specific mRNAs must be transcribed from the viral nucleic acid for successful expression and duplication of genetic information

Morphogenesis and Release

T

HANK YOU

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