INTRODUCTION TO VIROLOGY CONCEPTS

1. INTRODUCTION TO VIROLOGY

2. Background/Discovery
The concept behind modern virology can be traced back to Adolf
Mayer, Dimitri Ivanofsky and Martinus Beijerinck who,
independently in the late 1880’s, discovered what was later to be
called tobacco mosaic virus (TMV).
Their discoveries led to the descriptions of filterable agents, too
small to be seen with the light microscope, that could be grown in
living cells and cause disease.
The first filterable agent from animals, foot and mouth disease
virus, was described by Loeffler and Frosch in 1898 and the first
human filterable agent discovered was yellow fever virus, discovered
by Walter Reed in 1901.
The term ‘virus’ derives from the Latin for slimy liquid or poison
and was gradually introduced during this period to replace the term
‘filterable agents’.

3. •The first virus to be visualized by x-ray crystallography and electron
microscopy was TMV, reported in 1941 and 1939, respectively.
•These advances introduced the notion that viruses were structurally
composed of repeating subunits.
•
•Frederick Twort and Felix d’Herelle, working independently, are
credited with the discovery of viruses which could infect and lyse
bacteria in 1915.
•D’Herelle introduced the term ‘bacteriophages’ for these agents and
also described the concepts of virus adsorption to its target, cell lysis
and release of infectious particles.
•Over the next 35-40 years, work with phages led to numerous
discoveries including how the introduction of DNA into a target cell
could reproduce itself and the regulation of cellular macromolecular
synthesis directed by viruses.
•In essence, the field of molecular biology was opened up during
this period.

4. •Advances in animal virology were noted throughout the
20th century but the major breakthrough came through
the development of tissue culture systems that led, for
example, to the isolation of poliovirus by Enders et al. in
1949.
•This markedly facilitated detailed study of this agent and,
most importantly, the development of poliovirus vaccines.
•The ensuing 50 years have seen diagnostic virology
mature as a field with the discovery of new agents and
diseases and the parallel determination of the importance
of viruses in our understanding of molecular biology and
cancer.

5. A. As with other infectious agents which cause human disease, the
outcome of the interaction of a particular virus with the human host is
dependent on both pathogen and host factors. Viral strains within a
genus may have differential cell tropisms, replication capacities and
cytopathogenic effects. As an example, strains of HIV may preferentially
target monocyte/macrophages or T-lymphocytes, may use different co-
receptors (e.g., the chemokine receptors, CCR5 or CXCR4) on the cell
surface, may replicate to different levels and may induce different
degrees of cell killing. These traits have direct clinical correlates for HIV
infected persons with respect to the rates of CD4 cell decline and
progression to clinical AIDS. On the host side, the nature of the
exposure and the host immune status are probably the two most
important determinants of outcome.
Thus, the key elements of the virushost interaction are:
1. Viral strain.
2. Inoculum size.
3. Route of exposure.
4. Susceptibility of host (i.e., is there pre-existent immunity from past
exposure or vaccination?).
5. Immune status and age of host.

6. Definitions
A. Virus particle or virion.
An infectious agent composed of nucleic acid (RNA or DNA), a protein
shell (capsid) and, in some cases, a lipid envelope.
Virions have full capacity for replication when a susceptible target cell is
encountered.
1.Capsid and capsomeres. The protein coat that surrounds the viral
nuclei acid. This is composed of repeating protein 2 subunits called
capsomeres.
Generally, capsids have either helical or icosahedral symmetry.
2. Nucleocapsid. The complete protein-nucleic acid complex.
B. Satellite or Defective Viruses.
Viruses which require a second virus (helper virus) for replication.
Hepatitis delta virus is the major humanpathogen example.
It requires the presence of hepatitis B virus to complete its replication
cycle.

7. OR
Virus "poisonous substance," from Latin virus "poison
A virus is a chain of nucleic acids (DNA or RNA) which lives in
a host cell, uses parts of the cellular machinery to reproduce, and
releases the replicated nucleic acid chains to infect more cells.
A virus is often housed in a protein coat or protein envelope, a
protective covering which allows the virus to survive between hosts.

8. Terminology:
Virion = virus particle
Capsid = protein shell which surrounds and protects the genome. It is built up of
multiple (identical) protein sub-units called capsomers. Capsids are
either icosahedral or tubular in shape
Nucleocapsid = genome plus capsid
Envelope = lipid membrane which surrounds some viruses. It is derived from the
plasma membrane of the host cell
Peplomers = proteins found in the envelope of the virion. They are usually
glycosylated and are thus more commonly known as glycoproteins
Viroids. Viroids are the smallest known autonomously replicating molecules. They
consist of single-stranded, circular RNA, 240-375 residues in length and are plant
pathogens.
D. Prions. Prions are not viruses but are often discussed within this microbiologic category.
Prions are infectious protein molecules that contain no definable nucleic acid and are
responsible for the transmissible and familial spongiform encephalopathies: The
pathogenic prion protein, PrPSc, is formed from a normal human protein, PrPC , through
post-translational processing.

9. Virus Structure
A virus can take on a variety of different structures.
The smallest virus is only 17 nanometers, barely longer than an
average sized protein.
The largest virus is nearly a thousand times that size, at 1,500
nanometers.
This is really small. A human hair is approximately 20,000
nanometers across.
This means that most virus particles are well beyond the capability
of a normal light microscope. Below is a scanning electron
microscope (SEM) image of the Ebola virus.
The exact structure of a virus is dependent upon
which species serves as its host.
A virus which replicates in mammalian cells will have a protein coat
which enables it to attach to and infiltrate mammalian cells.
The shape, structure, and function of these proteins changes
depending on the species of virus. A typical virus can be seen below.

10. Viral Tegument

11.  The above virus shows the typical structure a virus takes, a viral genome
surrounded by a shield of proteins.
 The various envelope proteins will enable the virus to interact with the host cell
it finds. Part of the protein coat will then open, puncture through the cell
membrane, and deposit the viral genome within the cell.
 The protein coat can then be discarded, as the viral genome will now replicate
within the host cell.
 The replicated virus molecules will be packaged within their own protein coats,
and be released into the environment to find another host.
 While many virus particles take a simple shape like the one above, some are
much more complicated.

12. III. Classification
Viral classification has been confusing and oft-changing over the
years. In the past, viruses were often classified by host, target organ
or vector and these are still used vernacularly (e.g., the hepatitis
viruses).
Modern classification is based on the following three characteristics:
A. Type of viral nucleic acid (RNA or DNA, single-stranded or
double stranded) and its replication strategy.
B. Capsid symmetry (icosahedral or helical).
C. Presence or absence of lipid envelope.

14.  The above image shows a phage, a type of virus which specializes
on bacterial cells.
 The protein coat of a phage is much more complex, and has a
variety of specialized parts.
 The head portion contains the viral genome.
 The collar, sheath, base plate, and tail fibers are part of an
intricate system to attach to and inject the genome into a
bacterial cell.
 The tail fibers grasp the bacterial cell, pulling the base plate up to
the cell wall or membrane.
 The sheath and collar compress, puncture the cell, and deposit
the DNA into the bacterial cell.

15. Size
 Viruses are usually much smaller than bacteria with the vast
majority being submicroscopic.
 While most viruses range in size from 5 to 300 nanometers (nm) ,
in recent years a number of giant viruses, including Mimiviruses
and Pandoraviruses with a diameter of 0.4 micrometers (µm) ,
have been identified.
 For a comparison of the size of a virus, a bacterium, and a human
cell, scroll down to how big is... on the Cell Size and Scale
Resource at the University of Utah webpage
 (see Figure 1A, Figure 1B, and Figure 1C),

16. Figure 1A: Sizes and Shapes of Viruses (Animal RNA Viruses

17. Figure 1B: Sizes and Shapes of Viruses (Animal DNA Viruses)

18. Figure 1C: Sizes and Shapes of Viruses (Bacteriophages)

19. Figure 2: Viral Structure (Helical Virus). (B) Viral Structure (Polyhedral Virus), (C) Viral
Structure (Enveloped Helical Virus), D: Viral Structure (Enveloped Polyhedral Virus), (F)
Viral Structure (Binal) Illustration of a T-even bacteriophage consisting of a head,
sheath, and tail.

20. Is a Virus Living?
This is a complicated question. A cell is considered to be living
because it contains all the necessary components to replicate its
DNA, grow, and divide into new cells. This is the process all life
takes, where it is a single-celled organism or a multi-cellular
organism. Some people do not consider a virus living because a virus
does not contain all of the mechanisms necessary to replicate itself.
They would say that a virus, without a host cell, cannot replicate on
its own and is therefore not alive.
Yet, by the definition of life laid out before, it seems that when a
virus is inside of a host cell it does have all the machinery it needs to
survive. The protein coat it exists in outside of a cell is the equivalent
of a bacterial spore, a small capsule bacteria form around themselves
to survive harsh conditions. Scientists who support a virus being a
living organisms note the similarity between a virus in a protein coat
and a bacterial spore. Neither organism is active within their
protective coat, they only become active when they reach favorable
conditions.

21. Virus Classification

22. Classification of virus
1. On the Basis of Genetic Material Present
2. On the basis of the presence of a number of strands
3. On the Basis of Presence of Envelope
4. Virus Classification by Capsid Structure
5. On the Basis of Shapes of the Viruses
6. Classification of Virus on the Basis of Structure
7. On the Basis of the Type of Host
8. Classification of Virus on the Basis of Mode of
Transmission
9. Classification of Virus on the Basis of Replication
Properties and Site of Replication
10. Baltimore Classification

23. Classification of virus
 Viruses are small obligate intracellular parasites, which by definition contain
either a RNA or DNA genome surrounded by a protective, virus-coded protein
coat.
 Viruses range from the structurally simple and small parvoviruses and
picornaviruses to the large and complex poxviruses and herpesviruses.
 Viruses are classified on the basis of morphology, chemical composition, and
mode of replication.
 The viruses that infect humans are currently grouped into 21 families,
reflecting only a small part of the spectrum of the multitude of different
viruses whose host ranges extend from vertebrates to protozoa and from plants
and fungi to bacteria.

24. 1. On the Basis of Genetic Material Present
Viruses are small, nonliving parasites, which cannot replicate
outside of a host cell.
A virus consists of genetic information — either DNA or RNA —
coated by a protein.
Accordingly, they are classified as DNA viruses and RNA viruses.
The nucleic acid may be single or double stranded, circular or
linear, segmented or unsegmented

25. DNA viruses
As their name implies, DNA viruses use DNA as their genetic material.
Some common examples of DNA viruses are parvovirus, papillomavirus, and
herpesvirus.
DNA viruses can affect both humans and animals and can range from causing
benign symptoms to posing very serious health.
RNA viruses
The virus that possesses RNA as genetic material are called RNA viruses.
Rotavirus, polio virus, yellow fever virus, dengue virus, hepatitis C
virus, measles virus, rabies virus, influenza virus and Ebola virus are examples
of RNA virus.
DNA-RNA viruses
The RNA tumor viruses called Leukoviruses and Rous’s viruses unusually
contain both DNA and RNA as genetic material

26. 2. On the basis of the presence of a number of strands
Double-stranded DNA
It is found in pox viruses, the bacteriophages T2, T4, T6, T3,
T7 and Lamda, herpes viruses, adenoviruses etc.
Single-stranded DNA
It is found in bacteriophagesφ, X, 74 bacteriophages.
Double-stranded RNA
It has been found within viral capsid in the reoviruses of animals
and in the wound tumour virus and rice dwarf viruses of plants.
Single-stranded RNA
It is found in most of the RNA viruses eg: tobacco mosaic virus,
influenza virus, poliomyelitis, bacteriophage MS-2, Avian leukemia
virus.

27. 3. On the Basis of Presence of Envelope
The envelope is a lipid-containing membrane that surrounds some
virus particles. It is acquired during viral maturation by a budding
process through a cellular membrane
Virus encoded glycoproteins are exposed on the surface of the
envelope. These projections are called peplomers.
Enveloped Virus
DNA viruses: Herpesviruses, Poxviruses, Hepadnaviruses
RNA viruses: Flavivirus, Toga virus, Coronavirus, Hepatitis D,
Orthomyxovirus, Paramyxovirus, Rhabdovirus, Bunyavirus,
Filovirus
Retroviruses
Non-Enveloped Virus
DNA viruses- parvovirus, adenovirus and papovavirus.
RNA viruses- Picornavirus, Hepatitis A virus and Hepatitis E virus.

28. 4. Virus Classification by Capsid Structure
1. Naked icosahedral: Hepatitis A virus, polioviruses
2. Enveloped icosahedral: Epstein-Barr virus, herpes simplex
virus, rubella virus, yellow fever virus, HIV-1
3. Enveloped helical: Influenza viruses, mumps virus, measles
virus, rabies virus
4. Naked helical: Tobacco mosaic virus
5. Complex with many proteins: some have combinations of
icosahedral and helical capsid structures. Herpesviruses,
smallpox virus, hepatitis B virus, T4 bacteriophage.

30. 5. On the Basis of Shapes of the Viruses
Most of the animal viruses are roughly spherical with some
exceptions.
1. Rabies virus: Bullet shaped
2. Ebola virus: Filamentous shaped
3. Poxvirus: Brick shaped
4. Adenovirus: Space vehicle shaped

31. 6. Classification of Virus on the Basis of Structure
Cubical virus: They are also known as icosahedral symmetry virus
Eg. Reo virus, Picorna virus.
Spiral virus: They are also known as helical symmetry virus
Eg. Paramyxovirus, orthomyxovirus.
Radial symmetry virus: eg. Bacteriophage.
Complex virus: eg. Pox virus

32. 7. On the Basis of the Type of Host
The virus can be classified on the basis of the type of host.
They are:
1. Animal viruses
2. Plant viruses
3. Bacteriophage

33. Animal Viruses
 The viruses which infect and live inside the animal cell including
man are called animal viruses.
 Eg; influenza virus, rabies virus, mumps virus, poliovirus etc.
Their genetic material is RNA or DNA.
Plant Viruses
• The viruses that infect plants are called plant viruses. Their
genetic material is RNA which remains enclosed in the protein
coat.
• Some plant viruses are tobacco mosaic virus, potato virus, beet
yellow virus and turnip yellow virus etc.
Bacteriophages
 Viruses which infect bacterial cells are known as bacteriophage or
bacteria eaters.
 They contain DNA as genetic material. There are many varieties
of bacteriophages.
 Usually, each kind of bacteriophage will attack only one species or
only one strain of bacteria.

34. 8. Classification of Virus on the Basis of Mode of Transmission
Virus transmitted through respiratory route:
Eg, Swine flu, Rhino virus
Virus transmitted through faeco-oral route:
Eg. Hepatitis A virus, Polio virus, Rota virus
Virus transmitted through sexual contacts:
Eg. Retro virus
Virus transmitted through blood transfusion:
Eg. Hepatitis B virus, HIV
Zoonotic virus:
Virus transmitted through biting of infected animals;
Eg. Rabies virus, Alpha virus, Flavi virus

35. 9. Classification of Virus on the Basis of Replication Properties
and Site of Replication
Replication and assembly in cytoplasm of host:
All RNA virus replicate and assemble in cytoplasm of host cell
except Influenza virus
Replication in nucleus and assembly in cytoplasm of host:
Influenza virus, Pox virus
Replication and assembly in nucleus of host:
All DNA viruses replicate and assemble in nucleus of host cell except
Pox virus.
Virus replication through ds DNA intermediate:
All DNA virus, Retro virus and some tumor causing RNA
virus replicates through ds DNA as intermediates.
Virus replication through ss RNA intermediate:
All RNA virus except Reo virus and tumor causing RNA viruses.

36. 10 .Baltimore Classification
 The most commonly used system of virus classification
was developed by Nobel Prize-winning biologist David
Baltimore in the early 1970s.
 In addition to the differences in morphology and
genetics mentioned above, the Baltimore classification
scheme groups viruses according to how the mRNA is
produced during the replicative cycle of the virus.

40. Group I
 viruses contain double-stranded DNA (dsDNA) as their genome.
Their mRNA is produced by transcription in much the same way
as with cellular DNA.
Group II
 viruses have single-stranded DNA (ssDNA) as their genome. They
convert their single-stranded genomes into a dsDNA intermediate
before transcription to mRNA can occur.
Group III
 viruses use dsRNA as their genome. The strands separate, and one
of them is used as a template for the generation of mRNA using
the RNA-dependent RNA polymerase encoded by the virus.

41. Group IV
 This group viruses have ssRNA as their genome with a positive
polarity. Positive polarity means that the genomic RNA can serve
directly as mRNA.
 Intermediates of dsRNA, called replicative intermediates, are
made in the process of copying the genomic RNA.
 Multiple, full-length RNA strands of negative polarity
(complementary to the positive-stranded genomic RNA) are
formed from these intermediates, which may then serve as
templates for the production of RNA with positive polarity,
including both full-length genomic RNA and shorter viral
mRNAs.

42. Group V
 viruses contain ssRNA genomes with a negative polarity,
meaning that their sequence is complementary to the mRNA. As
with Group IV viruses, dsRNA intermediates are used to make
copies of the genome and produce mRNA.
 In this case, the negative-stranded genome can be converted
directly to mRNA.
 Additionally, full-length positive RNA strands are made to serve
as templates for the production of the negative-stranded
genome.

43. Group VI
 viruses have diploid (two copies) ssRNA genomes that must be
converted, using the enzyme reverse transcriptase, to dsDNA; the
dsDNA is then transported to the nucleus of the host cell and
inserted into the host genome.
 Then, mRNA can be produced by transcription of the viral DNA
that was integrated into the host genome.
Group VII
 viruses have partial dsDNA genomes and make ssRNA
intermediates that act as mRNA, but are also converted back into
dsDNA genomes by reverse transcriptase, necessary for genome
replication.

44. THANK YOU