VIROLOGI

Maxs U.E. Sanam

Maxisanam.wordpress.com Maxs U.E. Sanam.blogspot.com

VALUES

V VisionE ExcellenceT TargetE Effectiveness and EfficiencyR RationalI Integrity and honestyN Norm and EthicsE EnthusiasticR Rewarding and empathy

Historical Notes

• Viruses are too small to be seen with a light microscope and cannot be cultured outside their hosts.

• Viruses are not new; could not be studied untill 20th century

• In 1886, Adolf Mayer showed TMD was transmissible

• In 1892, Dimitri Iwanowski demonstrated infectious agent trapped in porcelain filter

• The first human disease associated with a filterable agent was Yellow fever

• Advances in the molecular biological techniques in the 1980s-1990 found several new human and animal viruses:– Human immunodeficiency virus (HIV)– Hepatitis C virus– SARS-associated coronavirus– West Nile virus

General Characteristics

• One hundred years ago, it was described as contagium vivum fluidum―a contagious fluid

• By the 1930s, the word ‘virus’ started to use• Virus, a latin word for poison, to describe

these filterable agents• Until 1935, Wendell Stanley isolated TMD• About the same time, Electron Microscope

(EM) was invented

Are viruses living organisms?

• has an ambigous answer• Life can be defined as a complex set of process

resulting from the actions of proteins specified by nucleic acids

• NA of living cells are in active all the time• Viruses are inert outside living host cells--- Viruses

are NOT alive• But once enter a host cell, the viral nucleic acids

become active, and viral multiplication results--- Viruses are ALIVE

• From clinical point of view, viruses are considered to be alive as they cause infection and disease (just as pathogenic bacteria, fungi, and protozoa do)

• Virus may be regarded as an exceptionally complex aggregation of nonliving chemicals, or

• An exceptionally simple living microorganism

How, then, do we define a virus?

• Virus are distinguished from other infectious agents:– small in size (filterable)– obligatory intracellular parasites

• However, both these properties are shared by certain small bacteria, such as some rickettsias

Viruses compared to bacteria

• The trully distinctive features of viruses are now known to relate to their:– Simple structural organization (only has nucleic

acids and capsid)– Mechanism of multiplication

Viruses are entities that:– Contain a single type of nucleic acid, either DNA or

RNA– Contain a protein coat (sometimes itself enclosed

by an envelope of lipids, proteins, and carbohydrates) that surrounds the nucleic acid

– Multiply inside living cells by using the synthesizing machinery of the cell

– Cause the synthesis of specialized structures that can transfer the viral nucleic acid to other cells

• Viruses have few or no enzymes of their own for metabolism; for example, they lack enzymes for protein synthesis and ATP generation

• To multiply, viruses must take over the metabolic machinery of the host cell

• Considerable medical significance for the development of antiviral drugs

How virus proliferates?

Host Range

• The host range of a virus is the spectrum of host cells the virus can infect

• There are viruses that infect invertebrata, vertebrata, plants, protists, fungi, and bacteria

• Most viruses are able to infect specific types of cells of only one hosts species

• In rare cases, viruses cross the host-range barrier• Viruses that infect bacteria are called

bacteriophages, or phages

Why the host range is limitted?

• The particular host range of a virus is determined by: – the virus’s requirements for its specific attachment to

the host cell, and– The availability within the potential host of cellular

factors required for viral multiplication

• For the virus to infect the host cell, the outer surface of the virus muct chemically interact with specific receptor sites on the surface of the cell

• For some bacteriophages, the receptor site is part of the cell wall of the host

• In other cases, it is part of the fimbriae or flagella• For animal viruses, the receptor sites are on the

plasma membrane of the host cells• Phage therapy―using bacteriaphage to treat

bacterial infections• Viral therapy for killing tumor cells (oncolytic) or

cause immune response against tumor cells

Structure of Bacteria

Viral Size• Viral size are determined with the aid of EM• Most are smaller than bacteria• Some larger viruses (vaccinia virus) are about

the same size as some very small bacteria than bacteria (such as mycoplasmas, rickettsias, and chlamydias)

• Viruses range from from 20 – 1000 nm in length

Size of viruses compared to bacteria & RBC

Structure of Virus

• Virion is a complete, fully developed, infectious viral particle composed of nucleic acid and surrounded by a protein coat

• The role of this protein coat:– Protect virus from the environment– A vehicle of transmission from one host cell to

another– Classification (based on its structure)

Nucleic acid

• Have either DNA or RNA―but never both

• Single-stranded (SS) or double-stranded (DS)

• DS DNA, SS DNA, DS RNA, SS RNA Viruses

• Depending on the virus, NA can be linear or circular

• In some virus (such as in the influenza virus), the NA is in several seperate segments

• The percentage of NA in relation to protein is about 1% for the influenza virus and about 50% for certain bacteriophage

• Total NA from thousand nucleotides (or pairs) to as many as 250,000 nucleotides (E. Cloi chromosome consists of approx. 4 million nucleotides)

Capsid and Envelope

• The NA is protected by a protein coat called capsid

• Accounts for most of the mass of a virus• Each capsid composed of protein subunits called

capsomers• The arrangements of capsomers is characteristic

of a particular type of virus• In some viruses, the capsid is covered by an

envelope

• Envelope consists of some combination of lipids, proteins, and carbohydrates

• In some viruses, the viral envolepe is derived from a layer of the host cell’s plasma membrane

• Depending on the virus, envelopes may or may not be covered by spikes

• Spikes are carbohydrate-protein complexes that project from the surface of the envelope

• Some virus attach to the host cell by means of spikes

• Spikes are a reliable characteristic of some virus, can be used for identification

• Spikes enable some virus, like the influenza virus and Newcatle disease virus (NDV) to clump red blood cells

• Viruses that do not have an envelope are known as nonenveloped or naked viruses

• Their NA are protected from nuclease enzymes by their capsid

• Capsid also promotes the virus’s attachment

Diagram of Influenza virus

• When the host has been infected by a virus, the host immune system is stimulated to produce antibodies

• Abs are proteins that react with the surface proteins of the virus

• This interaction should inactivate the virus and stop the infection

• However, some virus can escape antibodies because regions of the genes that code for these viruses’ surface proteins are susceptible to mutations

• Influenza virus frequently undergoes such changes in its spikes

GENERAL MORPHOLOGY

• Viruses may be classified into several different morphological types based on the basis of their capsid architecture

• The structure of these capsids has been revealed by EM and a technique called X-ray crystallography

• These morphological types are:– Helical viruses– Polyhedral viruses– Enveloped viruses– Complexed virus

Helical Viruses

, H V resembles long rods that may be rigid or flexible

The viral NA is found within a hollow, cylindrical capsid that has a helical structure

The virus that cause rabies and Ebola hemorrhagic fever are helical viruses

Polyhedral Viruses

Many animal, plant, and bacterial viruses are polyhedral, or many-sided, viruses

The capsid of most polyhedral viruses is in the shape of an icosahedron, a regular polyhedron with 20 triangular faces and 12 corners

The capsomers of each face form an aquilateral triangle.

Example of this is the adenovirus & poliovirus

Enveloped virus

The capsid is covered by an envelopeEnveloped viruses are roughly sphericalWhen helical or polyhedral viruses are enclosed by enveloped, they are called enveloped helical or enveloped polyhedral virusesExample is the influenza virus

Complex Viruses

• Some viruses, particularly bacterial viruses, have complicated structure and are called complex viruses

• Some bacteriophage have capsids to which additional structures are attached

• In this figure, notice that the capsid (head) is polyhedral and the tail sheath is helical

• The head contains the NA• Notice also other additional structures: the tail

sheath, tail fiber, plate, and pin

Bacteriophage

Summary of morphological types

Taxonomy of Viruses

• Help to organize and undestand newly discovered organisms

• The oldest classification was based on symptomatology (convenient but not scientifically acceptable as the same virus could cause > 1 disease)

• Virologist started to address th problem since 1966• The International Committee on Taxonomy of

Viruses (ICTV) was formed since then

• Viruses has been grouping into families based on:– (1) nucleic acid type– (2)strategy for replication– (3) morphology or the structure of the virion.

• Virus orders are designated by the suffix -virales. In orders, phylogenetically-related families are grouped together.

• Only two orders containing viruses of animals have been defined so far.

• These are the Mononegavirales comprising the families Paramyxoviridae, Rhabdoviridae, Bornaviridae and Filoviridae and the Nidovirales comprising the families Coronaviridae and Arteriviridae.

• The suffix -virinae denotes a subfamily. Viral genera are designated by the suffix -virus

• Of more than 50 families currently recognized, about 22 contain viruses of veterinary importance

• More than 230 genera are recognized

Species of viruses• The species taxon is regarded as the most important

level in the classification of viruses.• A viral species is a group of viruses sharing the same

genetic information and echological niche (host range)• Specific epithets for viruses are not used• Viral species are dessignated by descriptive common

names, such as Human immunodeficiency virus (HIV), with subspecies (if any) designated by a number (HIV-1)