HBT 2338: MEDICAL VIROLOGY

DR. PAUL NJENGA

SCHOOL OF PURE AND APPLIED SCIENCES
KIRINYAGA UNIVERSITY

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 CHAPTER ONE
INTRODUCTION TO MEDICAL VIROLOGY
 Virology is a field within microbiology that encompasses the study of viruses.
 Medical virology deals with the study of medically important viruses and the diseases
they cause or their effect on human beings.
 Viruses are particles consisting of protein and nucleic acid (an RNA or DNA genome).
 Lack both cellular structure and independent metabolic processes. They replicate solely
by exploiting living cells based on the information in the viral genome.
Germ theory of disease - Koch’s postulates
Koch defined four famous criteria, which are now known as Koch’s postulates and still
generally regarded as the proof that an infectious agent is responsible for a specific disease:

Virus diversity
 There is more biological diversity within viruses than in all the rest of the bacterial,
plant & animal kingdoms put together.
 This results from the success of viruses in parasitizing all known groups of living
organisms. Understanding this diversity is the key to comprehending the interactions
of viruses with their hosts.
 At a molecular level, protein-protein, protein-nucleic acid, & protein-lipid interactions
determine the structure of virus particles, the synthesis & expression of virus genomes

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 & the effects of viruses on the host cell.
Viruses are distinct from living organisms
 Viruses differ from other microorganisms in a number of characteristics:
i. They have no cellular structure, consisting only of proteins and nucleic acid (DNA
or RNA)
ii. They have no metabolic systems of their own, but rather depend on the synthetic
mechanism of a living host cell. Viruses exploit normal cellular metabolism by
delivering their own genetic information, i.e., nucleic acid, into the host cell. One
thus might call viruses “vagabond genes”
iii. Viruses infect other organism: bacteria (so-called bacteriophages), plants, animals,
and humans.
Are viruses are alive?
 One view is that inside the host cell, viruses are alive, whereas outside it they are merely
complex assemblages of metabolically inert chemicals.
 Chemical changes may occur in extracellular virus particles, but these are in no sense
the 'growth' of a living organism.
 Viruses are infectious agents with both living and nonliving characteristics.
Living characteristics of viruses:
i. They reproduce at a fantastic rate, but only in living host cells
ii. They can mutate
Nonliving characteristics of viruses:
i. They are acellular, that is, they contain no cytoplasm or cellular organelles;
ii. They carry out no metabolism on their own and must replicate using the host cell's
metabolic machinery.
Sub viral particles
1. Viroids
 They are very small (200-400 nucleotides) circular RNA molecules with a rod-like
secondary structure.
 They have no capsid or envelope & are associated with certain plant diseases.
2. Virusoids
 Are satellite, viroid-like molecules, somewhat larger than viroids (~1,000 nucleotides),
which are dependent on the presence of virus replication for multiplication (hence
'satellite’) - packaged into virus capsids as passengers.
3. Prions- are infectious agents generally believed to consist of a single type of protein
molecule with no nucleic acid component.
General Properties of Viruses
i. Viruses are smaller than bacteria, they range in size between 20-300 nanometer(nm)
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 ii. Viruses contain only one type of nucleic acid, either DNA or RNA, but never both.
iii. Viruses consist of nucleic acid surrounded by a protein coat(capsid). Some viruses have
additional lipoprotein envelope.
iv. Viruses lack cellular organelles, such as mitochondria and ribosomes.
v. Viruses are obligate cellular parasites. They replicate only inside living cells.
vi. Viruses replicate through replication of their nucleic acid and synthesis of the viral
protein.
vii. Viruses do not multiply in chemically defined media.
viii. Viruses do not undergo binary fission.
Comparison between viruses and bacteria:
No property Viruses Bacteria
1 Size 20-300 nm 1000nm
Genome (type of nucleic
2 acid) DNA or RNA but not both DNA and RNA
Envelope present in some
3 Cell wall viruses Cell wall
4 Ribosomes No Ribosomes Ribosomes
Multiplication by binary
5 fission - +
6 Sensitivity to antibiotics - +
Growth only in the living
7 Growth in culture media host cell Grow in chemical culture media
Reproduction of viruses
 Takes place only in living cells.
 The virus supplies;
i. The information in the form of nucleic acids
ii. A few enzymes (In some cases);
 The cell provides;
i. The remaining enzymes,
ii. The protein synthesizing apparatus,
iii. The chemical building blocks,
iv. The energy
v. The structural framework for the synthetic steps
Antibiotics
Viruses are unaffected by antibiotics, but can be inhibited by interferon and certain
chemotherapeutic agents.
The structure of viruses:
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 1. Viral nucleic acid:
 It is genetic materials responsible for virulence
 The viral nucleic acid is located internally and can be either single or double- stranded
RNA or DNA.
 The nucleic acid can be either linear or circular.
 The DNA is always a single molecule, the RNA can exist either as a single molecule
or in several pieces (segmented).
 Some RNA viruses are positive polarity and others are negative polarity.
Positive polarity is defined as an RNA with same base sequence as the mRNA. (positive
strand RNA)
Negative polarity has a base sequence that is complementary to the mRNA.
(Negative strand RNA).
2. Capsid:
 Consist of many small protein units called Capsomeres
 It is the protein shell, or coat, that encloses the nucleic acid genome.
Functions
i. Protection of from environment
ii. Organ of attachment of the virus to specific receptors on the host cell surface in non-
envelope virus (naked virus).
iii. Responsible for viral symmetry
3. Capsomeres
 Morphologic units seen in electron microscope.
 Each capsomere, consisting of one or several proteins.
 Naked viruses are composed of nucleic acid + capsid (nucleocapsid).

4. Viral Envelope:
 The envelope is a lipoprotein membrane composed of lipid derived from the host cell
membrane during release by budding and protein that is virus- specific.
 Furthermore, there are frequently glycoproteins in form of spike-like projections on
the surface, which attach to host cell receptors.
 Envelope sensitive to lipid solvent and detergent
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  Matrix protein mediates the interaction between the capsid proteins and enveloped
 The presence of an envelope confers instability on the virus.
Nucleic acid +capsid + envelope = enveloped Viruses

Viral Structural Patterns (Viral Symmetry)

1. Cubic Symmetry (Icosahedral)

• Have exactly 60 subunits on the surface of an icosahedron
• Have fivefold, threefold and twofold rotational symmetry

2. Helical symmetry
• The virion contains an elongated nucleocapsid
• The capsomeres are arranged round the spiral of nucleic acid
• Most helical viruses are enveloped

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3. Complex symmetry
• Does not conform to cubic or helical symmetry

Reaction to physical and chemical agents:

1.Heat and cold
 Viral infectivity is generally destroyed by heating at 50-60oC for 30 mint., Viruses can
be preserved at -90 oC or -196oC (liquid nitrogen) for longtime.
2.PH
 Viruses can be preserved at physiological pH (7.3).
3.Ether susceptibility:
 Ether susceptibility can be used to distinguish viruses that possess an envelope from those
that do not.
4. Detergents:
 Nonionic detergents solubilize lipid constituents of viral membranes.
 The viral proteins in the envelope are released Anionic detergents also solubilize viral
envelopes, in addition, they disrupt capsids into separated polypeptides.
5. Salts
 Many viruses can be stabilized by salt in concentrations of 1 mol/L. e.g. MgCl2, MgSO4,
Na2SO4.
6. Radiation
 Ultraviolet, X-ray, and high-energy particles inactivate viruses
7. Formaldehyde

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  Destroys viral infectivity by reacting with nucleic acid.
8. Antibiotics
 Antibacterial antibiotics have no effect on viruses.
Classification of viruses
 Names used for viruses should be those approved by the International Committee on
Taxonomy of Viruses (ICTV) and reported on the ICTV Virus Taxonomy website.
Bases of classifying viruses
Classification of viruses
1. Type of Nucleic Acid
 DNA or RNA (Ss /Ds)
 Strategy of replication
2. Size & morphology
 Type of symmetry (Icosahedral, Helical or Complex )
 Number of capsomers
 Presence or absence of envelope
3. Presence of specific enzymes
E.g: - RNA and DNA polymerase
- Neuraminidase
- Reverse transcriptase
4. Host tissue or cell tropism
E.g: Hepatitis viruses, HIV, etc
5.Mode of transmission e.g. Arboviruses
6. Host range E.g. Animal, bacteria, plant
7. Type of disease E.g. encephalitis

Baltimore classification
 The Baltimore classification clusters viruses into families depending on their type of
genome. Unlike LUCA (Last universal common ancestor) for cellular organism, there is
no presumed common ancestor for viruses.
 David Baltimore (nobel Prize 1975) proposed a classification based on the genome present
in virions.

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  Under the Balttimore system, the present virus classification comprises seven trees of life.

Baltimore system of classification

Naming of viruses
 Viruses are named based on;
i. The disease they cause- Eg. Poliovirus, rabies virus
ii. The type of disease- Eg. Murine leukemia virus
iii. Geographical location- Eg. Sendai virus, coxsackie virus
iv. Their discoverer- Eg. Epstein- Barr virus
v. How they were originally thought to be contracted- eg. dengue virus (‘evil spirits’),
influenza virus (the ‘influence’ of bad air)
vi. Combination of the above- eg. Rous Sarcoma virus

Virus infectious cycle (Virus Replications)

It involves the following steps
1. Adsorption or attachment
• Reactive sites on viruses’ surface interact with specific receptors on susceptible host cells
• Receptors on the virus capsid or envelope irreversibly binds to cellular receptors on the
cell member
2. Penetration
• The coat of enveloped viruses fuses with host cell member & release the virus nucleo-
capsid into host cytoplasm
• Other viruses enter into cell by endocytosis
3. Uncoating
• Viral capsid is broken by viral or cellular enzyme;

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 • Viral NA is released;
• Viral NA transported within the host cell
► Transcribed to form new progeny virions
4. Biosynthesis or genomic activation
• m-RNA transcribes from viral DNA or; formed directly from some RNA viruses & codes
for viral proteins
5. Assembly
• Assembly of viral nucleo- capsid may take place in:
a. Nucleus: E.g: Herpes virus, Adeno virus & others
b. Cytoplasm: E.g: Poliovirus
c. At the cell surface E.g: Influenza virus
6. Release
• Release of new intact infectious virions
• May occur by:
 Budding E.g: Enveloped viruses
 Lysis of infected host cells/ tissues

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