1. VIRUS-I
Md. Saiful Islam
B.Pharm, M.Pharm (PCP)
North South University
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2. What is a virus ?
• Viruses are submicroscopic, obligate intracellular
parasites
• Morphologically, virus particle is a protein shell, in
which the viral genome is enclosed
• Virus particles are produced from the assembly of
pre-formed components and do not grow or
undergo division
• Viruses lack the genetic information which encodes
apparatus necessary for the generation of metabolic
energy and for protein synthesis

3. The Viruses-
• Can infect every type of cell
• Cannot exist independently from the host cell, so
aren’t considered living things
• However, since they can direct life processes they
are often considered more than lifeless molecules
• Referred to as infectious particles, either active or
inactive
• Obligate intracellular parasites
• Cannot multiply unless they invade a specific host
cell and instruct its genetic and metabolic
machinery to make and release new viruses

6. The Search ?
• Viruses were too small to be seen with the first
microscopes
• The cause of viral infections was unknown for years
• Louis Pasteur first proposed the term virus
• 1890s
– Iwanowski and Beijerinck showed that a disease in
tobacco was caused by a virus
– Loeffler and Frosch discovered an animal virus
that causes foot –and-mouth disease in cattle
• Many years of experimentation showed what we know
today and by the 1950s virology had grown

7. History
• The first and foremost evidence of viruses responsible
for causing human disease came into notice in 1892 when
Iwanowski rightly demonstrated that the cell-free
extracts of the diseased tobacco leaves passed through
the bacteria-proof filters may ultimately cause disease in
the ‘healthy plants’.
• Such cell-free filtrates when cultured upon the bacterial
growth media they eventually exhibited practically little
growth thereby suggesting that the said filtrates contained
the actual disease causing agents that are other than
microorganisms.

8. TMV (Tobacco mosaic virus)
Pitch of
helix 22.8
Å
p=1.4Å (axial rise
per subunit)
m=16.3 (subunits per helix turn)

9. History
• Twort and d’Herrelle (1915) individually showed the
‘glassy phenomenon’ present very much in the
microorganisms when it was observed clearly and
distinctly that the bacterial cells might be adequately
infected with and duly destroyed by the filterable
agents, which in turn caused various serious diseases
both affecting the animal kingdom and the plant
kingdom.
• Later on, these disease producing filterable agents are
known as bacteriophages (i.e., the bacteria-eaters).
• Wendell M Stanley (1935), an American Chemist, first
and foremost isolated the tobacco mosaic virus (genus
Tobamovirus) thereby making it possible to perform the
chemical as well as structural studies on a purified virus.

10. History
• Interestingly, almost within the same time, the invention of
the electron microscope took place which eventually made it
quite possible to visualize the said viruses for the first time.
• Latest molecular biology techniques in the 1980s and 1990s
have remarkably led to the discovery of the new dreadful
human viruses.
• In the year 1989, the world has duly acknowledged the
discovery of Hepatitis C virus, and Pestivirus, which
specifically causes acute pediatric diarrhoea.
• In1993, critically observed the outbreak of a Hantavirus
infection occurring exclusively in the Southwestern USA,
which essentially possesses the potential for new infections
to emerge at any time.
• Hantavirus disease refers to the acute ailment related to
respirator disease and may even prove fatal.

11. The Composition
Common things to all
virus particles:
1. It encloses genomic
nucleic acid
2. It is a polymer,
assembled from one or
few different kinds of
monomers

12. Viral Structure
• Genetic material of a virus is either DNA or RNA, but
never both
• Protein coat is called CAPSID; surrounds the nucleic
acid core
• Capsid is composed of sub-units called CAPSOMERES
• Some viruses may have a lipid envelope around the
outside
• Envelope may or may not be covered with SPIKES

13. The nucleocapsid
• Nucleocapsid is the viral nuleic acid, enclosed in
the protein shell
• In case of simple non-enveloped viruses
nucleocaspsid and virus particle is the same
thing
• In enveloped viruses, lipid bilayer of cellular
origin encloses the nucleocapsid

14. Viral Structure
(Nonenveloped virus)

15. Enveloped Virus

16. Enveloped and non-enveloped viruses
• Non-enveloped virus • Enveloped virus
DNA or RNA genome
Nucleocapsid
Lipid
bilayer
Envelope protein
Matrix protein

18. Functions of the Viral Envelope
• Protects nucleic acids
• Help introduce the viral DNA or RNA into a suitable
host cell
• Stimulate the immune system to produce antibodies
that can protect the host cells against future infections

19. Spikes
• Hemagglutinin spikes
• 500 per virus
• Allows virus to
recognize and attach to
body cells
• Antibodies made to
these spikes
• Neuraminidase spikes
• 100 per virus
• Help virus separate
from infected host cell

20. The genomes
• I: Double-stranded DNA.
Examples: Adenoviruses, Herpesviruses, Papillomaviruses,
Poxiviruses,T4bacteriophage
• II: Single-stranded (+)sense DNA.
Examples: phage M13, chicken anaemia virus, maize streak virus
• III: Double-stranded RNA.
Examples:Reoviruses, Rotavirues
Genome- the sum total of the genetic information
carried by an organism

21. The genomes
• IV: Single-stranded (+)sense RNA
Examples: Hepatitis A and C, Small RNA phages,
common cold viruses, SARS (Severe acute
respiratory syndrome).

22. • V: Single-stranded (-)sense RNA.
Examples: Influenza viruses, Hantaviruses
.
VI: Single-stranded (+)sense RNA with DNA
intermediate in life-cycle (Retroviruses).
Examples: HIV, Avian leukosis virus
VII: Partial double-stranded (gapped) DNA with
RNA intermediate (Hepadnaviruses)
Example: Hepatitis B
The genomes

25. How Viruses are Classified and Named
• Main criteria
– Structure
– Chemical composition
– Similarities in genetic makeup
• International Committee on the Taxonomy of
Viruses, 2000
– 3 orders
– 63 famillies “-viridae”
– 263 genera “-virus”

27. The viral life cycle
•Initation phase:
a) Attachment to the host cell receptor (Ig like receptors,
cellular adhesion molecules, membrane transport proteins,
oligosaccharides, etc)
b) Penetration (endocytosis, fusion)
c) Uncoating
• Most bacteriophages avoid penetration and uncoating
stages by injecting the viral nucleic acid into the cell.
• Plant viruses do not use specific receptors and enter the cell
either through insect vectors or mechanically damaged parts
of plant.
• Some viruses initiate direct cell fusing. In this process
infected cell is fused with uninfected.

28. Initiation phase
Non-
enveloped
virus
Enveloped
virus

29. The viral life cycle
• Replication phase
a) nucleic acid replication
b) mRNA synthesis
c) protein expression
d) assembly
• Release phase
a) exit from cell (lysis, exocytosis, budding)
b) maturation (rearrangement of nucleocapsid, etc)

30. Inenvelopedviruses

31. Satellites: small RNA molecules, absolutely dependent
on presence of another virus
Type A: an RNA molecule of more than 700 nt, which encodes its
own capsid protein
Type B: an RNA molecule of more than 700 nt, which encodes a
non-structural protein
Type C: a linear RNA of less than 700 nt, which does not encode any
proteins
Type D: a circular RNA of less than 700 nt, which does not encode
any proteins
NT: Abbreviation for nucleotide; i.e. the monomeric unit
from which DNA or RNA are built. One can express the
size of a nucleic acid strand in terms of the number of
nucleotides in its chain; hence ‘nt’ can be a measure of
chain length.

32. Satellites
• Satellites often cause different symptoms than
the host virus alone
• Most known satellites are associatet with plants
(satellite tobaco necrosis virus, satellite
panicum mosaic virus, etc)
• Some are dependent on animal viruses – for
example dependoviruses, wich are satellites of
adenoviruses.

33. Different symptoms of infection by Tobacco
necrosis virus without (left) and with co-
infection of Tobacco sattelite necrosis virus

34. Viroids
• Viroids are very small (200-400 nt) rod-like RNA
molecules with a high degree of secondary structure
• Viroids do not encode any proteins and unlike
satellites they are not dependent on the presence of
another virus

35. Viroids
• Infectious RNA
• No protein coat
• Naked pieces of RNA that cause disease
• GOOD NEWS – viroids cause disease only in
plants, at least so far!

36. Examples of plants, infected with various viroids

37. Hepatitis D virus – a chimeric molecule, half
viroid, half satellite
• Viroid like properties
- Rod-like RNA molecule
- Central conserved region
similar to plant viroids
- Rolling circle replication
- Self-cleaving activity
• Satellite like properties
- Encodes a protein, which is
necessary both for
encapsidation and
replication
- Dependent on presence
another virus – HBV
- Genome larger than for
viroids (1640 nt)

38. Prions
• Infectious proteins!
• Naked protein molecules that cause disease and death
in humans
• Two well known prion diseases are SCRAPIE and MAD
COW DISEASE
• Human prion disease is variant Creutzfledt-Jakob
disease
• Disease causes fatal brain encephalitis

39. Virus Replication
1 Virus attachment
and entry
1 2 Uncoating of virion
2
3 Migration of
genome nucleic
acid to nucleus
3
4 Transcription
5 Genome replication
4
5
6 Translation of virus
mRNAs
6
7 Virion assembly
7
8 Release of new
virus particles
8

40. There are many variations on the virus replication and this
diagram illustrates some of the basic features of the cycle.
1. Attachment and entry: viruses recognise specific structures
on the cell surface (referred to as virus receptors), which target
the virus to specific cell types and tissue. This is one of the
primary determinants for which tissues are infected by a
particular virus. The receptor is a normal component of the cell,
which the virus has hijacked for the infection process.
2. Uncoating: The virion breaks open and releases the virus
genome nucleic acid into the host cell cytoplasm. Further
replication may take place in the cytoplasm or the nucleic acid
may migrate to the cell’s nucleus.
3. Transcription: Virus mRNA is produced using either cellular
enzymes or virus-coded enzymes.

41. 4.Genome replication: This stage can take place in either the
cytoplasm or nucleus of the infected cell. Depending on the size of
the virus genome the enzymes involved in genome replication may be
encoded by either the virus itself or the host cell.
5.Translation: This stage uses the host cell machinery - ribosomes
and enzymes etc. Various proteins are synthesised - structural - only
in virion - and non-structural - detected only in the virus-infected cell.
6. Virion Assembly: The newly formed virus proteins and genomic
nucleic acid assemble to produce the new virus particles.
7. Virion release: Various strategies are available for the release of
the progeny virus from the infected cell depending on the particular
virus group. The virus may bud through the cell membrane at which
time it picks up the envelope surrounding the virus particle OR the
virus may simply cause lysis of the cell resulting in cell death and the
release of progeny virus particles.

43. How are viruses categorized?
• Type of nucleic acid
• How they replicate
• Morphology

44. Bacterial Viruses
• Bacteriophage - from Greek phage in “to eat”
• Viruses that ONLY infect most types of
bacteria
• Phages may be the most common entities in
the biosphere
• Two cycles of viral multiplication
1. LYTIC CYCLE
2.LYSOGENIC CYCLE

45. 1.Lytic Cycle
• 1. Attachment- binding sites must match receptor sites on
host cell
• 2. Penetration - viral DNA is injected into bacterial cell
• 3. Biosynthesis
– Genome replication
– Transcription
– Translation
• 4. Assembly (Maturation)
– viral particles are assembled
• 5. Release
– Lysis
Virus uses Host Cells enzymes and machinery

48. Lysogeny: The Silent Virus Infection
• Temperate phages- special DNA phages that
undergo adsorption and penetration but are
not replicated or released immediately
• Instead the viral DNA enters an inactive
prophage stage
• Lysogeny: the cell’s progeny will also have the
temperate phage DNA
• Lysogenic conversion: is a change that is
induced the host phenotype by the presence of
a prophage.

49. 2. Lysogenic Cycle
• 1. Attachment
• 2. Penetration
• 3. Integration
– Viral Genome is integrated into Host Cell Genome
– Virus is “Latent”
– Prophage
• 4. Biosynthesis - Viral Genome is Turned On
– Genome replication
– Transcription
– Translation
• 5. Assembly
• 6. Release
– Lysis

50. Lysogenic Convergence
• 1. Corynebacterium diphtheriae
• 2. Streptococcus pyogenes
– Scarlet Fever
• 3. Clostridium botulinum

51. Lysogenic Cycle

52. Comparison of bacterial virus and animal
virus multiplication
• Bacterial
– Attachment
– Penetration
– Biosynthesis
– Maturation
– Release
• Animal
– Attachment
– Penetration
– Uncoating
– Biosynthesis
– Maturation
– Release

54. Techniques in Cultivating and Identifying Animal
Viruses
• Primary purposes of viral cultivation
– To isolate and identify viruses in clinical specimens
– To prepare viruses for vaccines
– To do detailed research on viral structure, multiplication cycles,
genetics, and effects on host cells
• Using Live Animal Inoculation
– Specially bred strains of white mice, rats, hamsters, guinea pigs, and
rabbits
– Animal is exposed to the virus by injection
• Using Bird Embryos
– Enclosed in an egg- nearly perfect conditions for viral propagation
– Chicken, duck, and turkey are most common
– Egg is injected through the shell using sterile techniques

55. Using Cell (Tissue) Culture Techniques
• Most viruses are propagated in some sort of cell
culture
• The cultures must be developed and maintained
• Animal cell cultures are grown in sterile chambers
with special media
• Cultured cells grow in the form of a monolayer
• Primary or continuous

56. Figure 6.22

57. Virus versus Virion
• Virus is a broad general term for any aspect of the
infectious agent and includes:
• the infectious or inactivated virus particle
• viral nucleic acid and protein in the infected cell
• Virion is the physical particle in the extra-cellular
phase which is able to spread to new host cells;
complete intact virus particle

59. Virus Structure
• consist of a core of nucleic acid surrounded
by a protein coat +/- envelope
• components of virus particle include:
i) nucleic acid - DNA or RNA
- single - or double - stranded
- intact / fragmented;
linear / circular
- encodes very few proteins

60. Virus Structure
ii) proteins:
a) structural - capsid made of capsomeres
- serve as antigens which elicit an
immune response
b) enzymes - differ from host cell
- targets of antiviral therapy
iii) envelope - found in some viruses;
- lipoprotein envelope containing
viral and host cell components
- destroyed by lipid solvents

61. Influenza Virus

62. Smallpox Virus

63. Herpesviridae

64. Outcome of Viral Infections
Virus-host cell interaction may result in:
1. Cell death (lytic) - due to cytopathic effect of virus
2. Cell transformation - cell converted to malignant
or cancerous cell
3. Latent infection (occult) - persistent infection in
quiescent state which may reactive anytime to
produce disease; continuous or intermittent
shedding
4. Cell fusion to form multinucleated cells

65. Persistent Viral Infections
3 types of persistent viral infection (some
overlap):
1. Chronic carrier - eg. Hepatitis B; results
in chronic illness
2. Latent infection - eg. Herpesviridae;
result in symptomatic or asymptomatic
shedding
3. Slow virus infections - due to prolonged
incubation period (eg. Measles virus and
SSPE)