VIRUSES

Where Did Viruses Come From?

There is much debate among virologists about this question. Three main hypotheses have been articulated:

1. The progressive (or escape) hypothesis: It states that viruses arose from genetic elements that gained the
ability to move between cells
2. The regressive (or reduction) hypothesis: It asserts that viruses are remnants of cellular organisms
3. The virus-first hypothesis: This states that viruses predate or coevolved with their current cellular hosts

The Progressive Hypothesis

According to this hypothesis, viruses originated through a progressive process. Mobile genetic elements, pieces
of genetic material capable of moving within a genome, gained the ability to exit one cell and enter another.

The Regressive Hypothesis

In contrast to the progressive process just described, viruses may have originated via a regressive or reductive
process. Microbiologists generally agree that certain bacteria that are obligate intracellular parasites,
like Chlamydia and Rickettsia species, evolved from free-living ancestors. Indeed, genomic studies indicate that
the mitochondria of eukaryotic cells and Rickettsia prowazekii may share a common, free-living ancestor. It
follows, then, that existing viruses may have evolved from more complex, possibly free-living organisms that
lost genetic information over time as they adopted a parasitic approach to replication.

The Virus-First Hypothesis

The progressive and regressive hypotheses both assume that cells existed before viruses. What if viruses existed
first? Recently, several investigators proposed that viruses may have been the first replicating entities. These
scientists postulated that viruses existed in a pre-cellular world as self-replicating units. Over time these units,
they argue, became more organized and more complex. Eventually, enzymes for synthesising membranes and
cell walls evolved, resulting in the formation of cells. Viruses, then, may have existed before bacteria, archaea,
or eukaryotes.

No Single Hypothesis May Be Correct

Where viruses came from is a complex question to answer. Perhaps today's viruses arose multiple times via
multiple mechanisms. Perhaps all viruses arose via a mechanism yet to be uncovered. Today's basic research in
fields like microbiology, genomics, and structural biology may provide us with answers to this fundamental
question.
Contemplating the origins of life fascinates both scientists and the general public. Understanding the
evolutionary history of viruses may shed some light on this interesting topic. To date, no clear explanation for
the origin(s) of viruses exists. Viruses may have arisen from mobile genetic elements that gained the ability to
move between cells. They may be descendants of previously free-living organisms that adapted a parasitic
replication strategy. Perhaps viruses existed before, and led to the evolution of cellular life. Continuing studies
may provide us with clearer answers. Or future studies may reveal that the answer is even more obscured than it
now appears.

The concept of virus

Edward Jenner (1798) introduced the term virus in microbiology. Virus in Greek means poison. Edward Jenner
noticed that milk maids who were infected with cowpox develop immunity against smallpox. He inoculated a
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boy with the vesicle fluid taken from the hand of an infected milk maid. The boy developed sustained immunity
against smallpox. Edward Jenner assumed that the vesicle fluid that has been taken from the hand of the milk
maid contained a poison (virus), that was responsible for immunity.

General characteristics of viruses

1. Viruses are smaller than bacteria, they range in size between 20-300 nanometer (nm).

2. Viruses contain only one type of nucleic acid, either DNA or RNA, but never both.
3. Viruses consist of nucleic acid surrounded by a protein coat. Some viruses have additional lipoprotein
envelope.
4. Viruses lack cellular organelles, such as mitochondria and ribosomes.
5. Viruses are obligate cellular parasites. They replicate only inside living cells.
6. Viruses replicate through replication of their nucleic acid and synthesis of the viral protein.
7. Viruses do not multiply in chemically defined media.
8. Viruses do not undergo binary fission.

CLASSIFICATION OF VIRUSES

Taxonomy A scheme of classification, especially a hierarchical classification, in which

things are organized into groups

Classification The arrangement of living things in taxonomic groups according to their

observed similarities

Nomenclature Assigning names to things

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How can viruses be classified?

a) On the Basis of Genetic Material Present

b) On the basis of the presence of a number of strands
c) On the Basis of Presence of Envelope
d) Virus Classification by Capsid Structure
e) On the Basis of Shapes of the Viruses
f) Classification of Virus on the Basis of Structure
g) On the Basis of the Type of Host
h) Classification of Virus on the Basis of Mode of Transmission
i) Classification of Virus on the Basis of Replication Properties and Site of Replication
j) Baltimore Classification of Viruses

How are viruses named?

The naming of viruses has so far been based on several properties including:
- the disease they cause e.g poliovirus, rabies virus
- the type of host/disease e.g murine leukemia virus
- geographic locations e.g Sendai virus, Coxsackie virus
- their discoverers e.g Epstein-Barr virus (Anthony Epstein, Yvonne Barr, Bert Achong)
- how they were originally thought to be contracted e.g dengue virus (“evil spirit”), influenza virus (the
“influence” of bad air)
- combinations of the above e.g Rous Sarcoma virus
Coronavirus?????

Initially viruses were classified according to the hosts they invaded and by the diseases they caused. As more
was learned about viruses, the early concept of “one virus, one disease” used in classification was found to be
invalid for many viruses. Today viruses are classified by chemical and physical characteristics such as the type
and arrangement of their nucleic acids, their shape, the symmetry of the protein coat that surrounds the nucleic
acid, and the presence or absence of a membrane covering (called an envelope), enzymes, tail structures, or
lipids.

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Currently there are two main schemes used for the classification of viruses: The Baltimore classification system,
which places viruses into one of seven groups. Accompanying this broad method of classification are specific
naming conventions and further classification guidelines set out by the International Committee on Taxonomy
of Viruses (ICTV).

The Baltimore Classification of viruses

The most commonly used system of virus classification was developed by Nobel Prize-winning biologist David
Baltimore in the early 1970s.
It places viruses into one of seven groups depending on:
1. their nucleic acid (DNA or RNA)
2. their strandedness (single-stranded or double-stranded)

3. sense (by convention the top strand of coding DNA written in the 5' - 3' direction is + sense. mRNA
sequence is also + sense)

4. their method of replication (the replication strategy of the virus depends on the nature of its genome)

These groups are designated by Roman numerals (I -VII). Viruses can be placed in one of the seven following
groups:

 I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses)

 II: ssDNA viruses (+ strand or "sense") DNA (e.g. Parvoviruses)
 III: dsRNA viruses (e.g. Reoviruses)
 IV: (+)ssRNA viruses (+ strand or sense) RNA (e.g. Picornaviruses, Togaviruses)
 V: (−)ssRNA viruses (− strand or antisense) RNA (e.g. Orthomyxoviruses, Rhabdoviruses)
 VI: ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses)
 VII: dsDNA-RT viruses (e.g. Hepadnaviruses)

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Group I: Double-stranded DNA viruses
These types of viruses must enter the host nucleus before it is able to replicate. Furthermore, these viruses
require host cell polymerases to replicate the viral genome. Proper infection and production of progeny requires
that the cell be in replication, as it is during replication that the cell's polymerases are active. The virus may
induce the cell to forcefully undergo cell division, which may lead to transformation of the cell and, ultimately,
cancer. Examples include Herpesviridae, Adenoviridae, and Papovaviridae. One well-studied example in which
a class 1 virus is not replicating within the nucleus is the Poxvirus family, a highly pathogenic virus that infects
vertebrates and includes the smallpox virus. The mRNA is transcribed in the normal way from viral DNA using
the host transcriptase enzymes.
Group II: Single-stranded DNA viruses – positive sense
Viruses in this category include viruses in the family Parvoviridae. Most of them have circular genomes (the
parvoviruses are the only known exception). Eukaryote-infecting viruses replicate mostly within the nucleus -
usually via a ‘rolling circle’ mechanism, forming double-stranded DNA intermediate in the process.
Group III: Double-stranded RNA viruses
As with most RNA viruses, this class replicates in the cytoplasm, not having to use the host replication
polymerases like the DNA viruses. This family is also not as well-studied as the rest and includes 2 major
families, the Reoviridae and Birnaviridae. Replication is monocistronic and includes individual, segmented
genomes, meaning that each of the genes codes for only one protein, unlike other viruses that exhibit more
complex translation.
Group IV: Single-stranded RNA viruses - positive-sense
The positive-sense RNA viruses and indeed all RNA defined as positive-sense can be directly accessed by host
ribosomes to immediately form proteins. These can be divided into two groups, both of which reproduce in the
cytoplasm:
 Viruses with polycistronic mRNA where the genome RNA forms the mRNA and is translated into a
polyprotein product that is subsequently cleaved to form the mature proteins. This means that the gene
can utilize a few methods in which to produce proteins from the same strand of RNA, all in the sake of
reducing the size of its gene.
 Viruses with complex transcription, for which subgenomic (smaller sections of the original transcribed
template stand) mRNAs, ribosomal frameshifting, and proteolytic processing of polyproteins may be
used. All of which are different mechanisms with which to produce proteins from the same strand of
RNA.

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Examples of this class include the families Astroviridae, Caliciviridae, Coronaviridae, Flaviviridae,
Picornaviridae, Arteriviridae, and Togaviridae.

Group V: Single-stranded RNA viruses - negative-sense

The negative-sense RNA viruses and indeed all genes defined as negative-sense cannot be directly accessed by
host ribosomes to immediately form proteins. Instead, they must be transcribed by viral polymerases into a
"readable" form, which is the positive-sense reciprocal. These can also be divided into two groups:
 Viruses containing nonsegmented genomes for which the first step in replication is transcription from
the (-)-stranded genome by the viral RNA-dependent RNA polymerase to yield monocistronic mRNAs
that code for the various viral proteins. A positive-sense genome copy is then produced that serves as
template for production of the (-)-strand genome. Replication is within the cytoplasm.
 Viruses with segmented genomes for which replication occurs in the nucleus and for which the viral
RNA-dependent RNA polymerase produces monocistronic mRNAs from each genome segment. The
largest difference between the two is the location of replication.
Examples in this class include the families Arenaviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae,
Filoviridae, and Rhabdoviridae (the latter which includes rabies).

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Group VI: Positive-sense single-stranded RNA viruses that replicate through a DNA intermediate
A well-studied family of this class of viruses include the retroviruses. One defining feature is the use of reverse
transcriptase to convert the positive-sense RNA into DNA. Instead of using the RNA for templates of proteins,
they use DNA to create the templates, which is spliced into the host genome using integrase. Replication can
then commence with the help of the host cell's polymerases.
Group VII: Double-stranded DNA viruses that replicate through a single-stranded RNA intermediate
This small group of viruses, exemplified by the Hepatitis B virus (which is in the Hepadnaviridae family), have
a double-stranded, gapped genome that is subsequently filled in to form a covalently closed circular DNA
(cccDNA) that serves as a template for production of viral mRNAs and a subgenomic RNA. The pregenome
RNA serves as template for the viral reverse transcriptase for production of the DNA genome.

Schematic representation of virus genome replication

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most of the nucleic acid strands are labelled (+) or (−). This labelling is relative to the virus mRNA, which is
always designated (+). A nucleic acid strand that has the same sequence as mRNA is labeled (+) and a nucleic
acid strand that has the sequence complementary to the mRNA is labelled (−).

The Committee on Taxonomy of Viruses (ICTV) classification of viruses

The International Committee on Taxonomy of Viruses (ICTV) is a committee of the Virology Division of the
International Union of Microbiological Societies. The ICTV is not responsible for classification and
nomenclature of virus taxa below the rank of species. The classification and naming of serotypes, genotypes,
strains, variants and isolates of virus species is the responsibility of acknowledged international specialist
groups.

Taxa will be established only when representative member viruses are sufficiently well characterized and
described in the published literature so as to allow them to be identified unambiguously and the taxon to be
distinguished from other similar taxa.

Rules about naming Taxa

Names proposed for taxa are "valid names" if they conform to the Rules set out in the Code and they pertain to
established taxa. Valid names are "accepted names" if they are recorded as approved International Names in the
ICTV Report or have subsequently become "accepted names" by an ICTV vote of approval for a taxonomic
proposal.

The universal system for classifying viruses, and a unified taxonomy, has been established by the International
Committee on Taxonomy of Viruses (ICTV) since 1966. The system makes use of a series of ranked taxa,
starting at the level of Order and continues as follows, with the taxon suffixes given in brackets:
Order (-virales) being the highest currently recognised.
then Family (-viridae)
Subfamily (-virinae)
Genus (-virus)
Species ( eg: Tobacco mosaic virus)
Species names generally take the form of [Disease] virus

MORPHOLOGY OF VIRUSES

Viruses have an amazing variety of shapes and sizes. They are very small and are measured in nanometers,
which is one-billionth of a meter. Viruses can range in the size between 20 to 750nm, which is 45,000 times
smaller than the width of a human hair. The majority of viruses cannot be seen with a light microscope because
the resolution of a light microscope is limited to about 200nm, so a scanning electron microscope is required to
view most viruses.
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The basic structure of a virus is made up of a genetic information molecule and a protein layer that protects that
information molecule. The arrangement of the protein layer and the genetic information come in a variety of
presentations. All viruses contain:
1. A nucleic acid genome
2. A protein coat (called capsid) that covers the genome.
Both structures are called the nucleocapsid. In addition, many animal viruses contain
3. A lipid envelope.
When a single virus is in its complete form and has reached full infectivity outside of the cell, it is known as a
virion.

A virus structure can be one of the following: icosahedral, enveloped, complex or helical.

Icosahedral
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These viruses appear spherical in shape, but a closer look actually reveals they are icosahedral. The icosahedron
is made up of equilateral triangles fused together in a spherical shape. This is the most optimal way of forming a
closed shell using identical protein sub-units. The genetic material is fully enclosed inside of the capsid. Viruses
with icosahedral structures are released into the environment when the cell dies, breaks down and lyses, thus
releasing the virions.
Examples of viruses with an icosahedral structure are the poliovirus, rhinovirus, and adenovirus.

Envelope
This virus structure is a conventional icosahedral or helical structure that is surrounded by a lipid bilayer
membrane, meaning the virus is encased or enveloped. The envelope of the virus is formed when the virus is
exiting the cell via budding, and the infectivity of these viruses is mostly dependent on the envelope. The most
well known examples of enveloped viruses are the
influenza virus, Hepatitis C and HIV.

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Enveloped icosahedral virus

Envelope helical virus

Complex

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These virus structures have a combination of icosahedral and helical shape and may have a complex outer wall
or head-tail morphology. The head-tail morphology structure is unique to viruses that only infect bacteria and
are known as bacteriophages. The head of the virus has an icosahedral shape with a helical shaped tail. The
bacteriophage uses its tail to attach to the bacterium, creates a hole in the cell wall, and then inserts its DNA
into the cell using the tail as a
channel. The Poxvirus is one of the largest viruses in size and has a complex structure with a unique outer wall
and capsid. One of the most famous types of poxviruses is the variola virus which causes smallpox.

Helical
This virus structure has a capsid with a central cavity or hollow tube that is made by proteins arranged in a
circular fashion, creating a disc like shape. The disc shapes are attached helically
creating a tube with room for the nucleic acid in the middle. All filamentous viruses are helical in shape. They
are usually 15-19nm wide and range in length from 300 to 500nm depending on the genome size. An example
of a virus with a helical symmetry is the tobacco mosaic virus.

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 REPLICATION OF VIRUSES

1. Adsorption (attachment): Viruses must recognize and bind to specific cellular receptors on the surface
of the infected cell via particular glycoproteins. Attachment is mediated by cell-surface molecule(s) and
viral spike proteins. For example HIV gp120 is specific for CD4. CD4 is principally found on helper T
cells. Attachment occurs by noncovalent interactions.

2. Penetration (entry): Enveloped viruses that have the ability to form syncytia ( multi-nucleated giant
cells ) enter the cell through fusion of the viral envelope with cell plasma membrane( eg. herpes
viruses ).

The remaining enveloped viruses enter the cell through endocytosis.

Unenveloped viruses enter the cell either by endocytosis ( endosome lyses as with adenoviruses) or by
forming a pore in the membrane of the cell. The viral RNA is then released inside the cell
(picornaviruses).

Endocytosis involves invagination of the cell membrane to form vesicles in the cell cytoplasm. Infected viruses
are then engulfed inside these vesicles. Each vesicle fuses with a lysosome to form lysosomal vesicle. The viral
envelope fuses with lysosomal membrane and the viral nucleocapsid is expelled into the cytoplasm.

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In either case, the capsid, containing the nucleic acid and viral enzymes, is released into the cytoplasm

3. Targeting to site of viral replication.

Most DNA viruses replicate in the nucleus
Most RNA viruses replicate in the cytoplasm
Some viruses integrate their dsDNA into the host cell’s genome (i.e., chromosomes)
Some viruses copy their RNA into dsDNA, which is then integrated into the host cell’s genome
4. Uncoating: Release of the viral genome from its protective capsid to enable the viral nucleic acid to
replicate.
The capsid is composed of protein subunits
The nucleic acid dissociates from the subunits
This causes the capsid to disintegrate, liberating the nucleic acid.
5. Nucleic acid replication and protein synthesis.
RNA viruses
Some RNA virus genomes act as a mRNA (”plus-strand” viruses)

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 All others (minus-strand viruses) possess a prepackaged, virus-encoded RNA-dependent
RNA polymerase
DNA viruses encode RNA polymerases
Many viruses have polycistronic mRNAs
Viral polypeptides are synthesized by the cell’s translational machinery

6. Maturation and assembly:

Cleavage of polycistronic polypeptides into subunits

HIV gp160 polypeptide is cleaved into its gp120 and gp41 mature polypeptides
This step is inhibited by the HIV protease inhibitors taken by HIV+ patients
Nucleic acids and capsid proteins spontaneously polymerize into nucleocapsid

7. Release.
Some viruses rely upon cell lysis for release into the extracellular environment
Other viruses rely upon budding, whereby they exit from the cell, taking part of its membrane
(viral envelope)
Budding occurs at the plasma membrane, ER or Golgi, depending on the viral species
If the rate of budding exceeds the rate of membrane synthesis, then the cell will die

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Assignment - MS Word
FUNGI
(modalities)
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- MORPHOLOGY

- PHYSIOLOGY

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