Section II - Virology By Dr. Kareem Lilo
1. General structure and classification of viruses
General properties 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
7. Viruses do not multiply in chemically defined media.
8. Viruses do not undergo binary fission.
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
complete intact virus particle is able to spread to new host cells; complete intact virus particle.
Table ( 2-1) : Comparison between viruses and bacteria
Section II - Virology By Dr. Kareem Lilo
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
• Negative polarity has a base sequence that is complementary to the mRNA. (Negative strand
The protein shell, or coat, that encloses the nucleic acid genome and
mediates the attachment of the virus to specific receptors on the host
Morphologic units seen in electron microscope. Each capsomere,
consisting of one or several proteins.
Naked viruses are composed of nucleic acid + capsid (nucleocapsid)
Figure 2-1 Naked virus composition
Section II - Virology By Dr. Kareem Lilo
The envelope is a lipoprotein membrane composed of lipid derived from the host cell membrane
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.
Matrix protein mediates the interaction between the capsid proteins and envelope.
The presence of an envelope confers instability on the virus Enveloped viruses NA
The whole virus particle is called virion. (Figure 2-2)
Types of symmetry of virus particles: (Figure 2-3)
Viruses are divided into three groups, based on the morphology of the nucleocapsid and the
Composed of 12 vertices, has 20 faces (each an equilateral triangle) with
the approximate outline of a sphere.
e.g. Virus that cause yellow fever and Poliovirus
Figure 2-2 illustrate the difference between enveloped virus and naked virus
Section II - Virology By Dr. Kareem Lilo
The virus particle is elongated or pleomorphic (not spherical), and the nucleic acid is spiral.
Caposomeres are arranged round the nucleic acid.
The virus particle does not confirm either cubic or helical symmetry
Reaction to physical and chemical agents:
Viral infectivity is generally destroyed by heating at 50-60 C0 for 30
mint., Viruses can be preserved at -90 C0 or
Viruses can be preserved at physiological PH (7.3).
Ether susceptibility can be used to distinguish viruses that possess
an envelope from those that do not.
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.
Figure( 2-3) Types of symmetry of virus particles
Section II - Virology By Dr. Kareem Lilo
Many viruses can be stabilized by salt in concentrations of 1 mol/L.
Ultraviolet, X-ray, and high-energy particles inactivate viruses.
Destroys viral infectivity by reacting with nucleic acid.
Antibacterial antibiotics have no effect on viruses.
1. Virion morphology, including size, shape, type of symmetry,presence or absence of
2. Virus genome properties, including type of nucleic acid (DNA or RNA), size of genome,
strandedness (single or double), whether linear or circular, positive or negative sense
(polarity), segments (number, size).
3. Physicochemical properties of the virion, including PH stability,thermal stability, and
susceptibility to physical and chemical agents,especially ether and detergents.
4. Virus protein properties, including number, size and functional activities of structural
and non-structural proteins, amino acid sequences, and special functional activities
(transcriptase, reverse transcriptase, neuraminidase, fusion activities).
5. Genome organization and replication, including gene order, strategy of replication
(patterns of transcription, translation), and cellular sites (accumulation of proteins,
virion assembly, virion release).
7. Biological properties, including natural host range, mode of transmission, vector
relationships, pathogenicity, tissue tropisms, and pathology.
Universal system of virus taxonomy:
Families – on the basis of virion morphology, genome structure and
Virus family names have the suffix – viridae.
Genera – based on physicochemical or serological differences.
Genus names carry the suffix – virus.
Section II - Virology By Dr. Kareem Lilo
• Parvoviruses: human parvovirus B19
• Papovaviruses: papillomaviruses
• Adenoviruses: 47 types infect humans
• Herpesviruses: human herpesvirus 1-8
• Poxviruses: smallpox; vaccinia
Viral Replication : ( Figure 2-4)
This is the first step in viral replication. Surface proteins of the virus interact with specific
receptors on the target cell surface.
Section II - Virology By Dr. Kareem Lilo
Enveloped with the viruses (e.g., HIV, influenza virus)penetrate cells through fusion of the viral
envelope host cell membrane. Non-enveloped viruses penetrate cells by translocation of the
virion across the host cell membrane or receptor mediated endocytosis .
This process makes the nucleic acid available for transcription to permit multiplication of the
D. Transcription and Translation:
The fact that viruses must use host cellular machinery to replicate and make functional and
Assembly and Release. The process of virion assembly involves bringing together newly formed
viral nucleic acid and the structural proteins to form the nucleocapsid of the virus
This is a necessary step to maintain a viral infection in populations of hosts. Shedding usually
occurs from the body surfaces involved in viral entry. Shedding occurs at different stages of
disease depending on the particular agent involved .
Figure (2-4) steps of viral replication
Section II - Virology By Dr. Kareem Lilo
- Acute (rapid and self-limiting)
- Latent (extreme versions of persistent infections)
- Slow or transforming (complicated types of persistent infections
Viral pathogenesis is the process by which a viral infection leads to disease.
A virus must first attach to and enter cells of one of the body surfaces: skin, respiratory tract,
gastrointestinal tract, urogenital tract, or conjunctiva.
Major exceptions are those viruses that are introduced directly into the bloodstream by needles
(hepatitis B, human immunodeficiency virus [HIV]), by blood transfusions, or by insect
Viruses usually replicate at the primary site of entry. Some, such as common cold viruses and
rotaviruses produce disease at the portal of entry and have no necessity for further systemic
Many viruses produce disease at sites distant from their point of entry. Spread within the host .
Mechanisms of viral spread vary, but the most common route is via the bloodstream or
lymphatics. The presence of virus in the blood is called viremia
• Inhalation ;e.g influenza viruses
• Transplacental, cytomegalovirus ,rubella.
Following infection the virus is transmitted by blood, cells, along nerves and become localized
in certain tissue which it prefer (tropism) e.g. polio, rabies etc.
1. Inhibits host cell DNA, RNA or protein synthesis e.g. Poliovirus.
2. Direct cell killing by damaging host cell membrane e.g. Rhinoviruses.
3. Induce Immune reaction e.g hypersensitivity reaction in respiratory cyncytial viruses.
Section II - Virology By Dr. Kareem Lilo
4. Damage host defiance mechanism e.g. respiratory epithelium predisposes to the
5. Induce cell proliferation & transformation result in neoplasia e.g. HBV, EBV.
Chemotherapy of Viral Infections :
Anti-bacterial drugs such as the penicillin antibiotics have proved very successful since they act
against a bacterial structure, the cell wall that is not present in eukaryotic cells.
In contrast, most anti-viral agents have proved of little use therapeutically since the virus uses
A successful anti-viral drug should:
(i) interfere with a virus-specific function.
(ii) interfere with a cellular function so that the virus cannot replicate. To be
specific, the anti-viral drug must only kill virus-infected cells
symptomatic rabies or hemorrhagic fever.
Antiviral drugs specifically inhibit one or more steps of virus replication without causing
unacceptable side effects. (Figure 2-5)
Because of the close interaction between virus replication and normal cellular metabolism, it was
originally thought too difficult to interrupt the virus replicative cycle without adversely
affecting the host cell metabolism.
Section II - Virology By Dr. Kareem Lilo
The life cycle of a virus comprises several stages such as binding to the cell surface, replication,
protein synthesis etc. and all of these stages may be the target of anti-viral drugs.
The mechanism of action vary among antiviral :
1. Nucleoside and nucleotide Analogs:
The majority of available antiviral agents are nucleoside analogs. They inhibit nucleic acid by
inhibition of polymerases essential for nucleic acid replication. In addition, some analogs can
be incorporated into the nucleic acid and block further synthesis or alter its function .
Example for nucleoside analogs include acyclovir , lamivudine ,ribavirin and zidovudine : AZT
Acyclovir (Zovirax) represents a major breakthrough in the treatment of herpes virus infections.
The main indications for its use are primary genital herpes
Nucleotide analogs differ from nucleoside analogs in having an attached phosphate group, their
ability to persist in cells for long periods of time increases their potency Cidofovir is an
2. Reverse transcriptase inhibitor :
It acts by binding directly to reverse transcriptase and disrupting the enzyme’s catalytic site, for
Saquinavir was the first protease inhibitor to be approved for treatment of HIV infection , which
inhibit viral protease that is required for the last stage of replicative cycle . Inhibition of the
protease yields noninfectious virus particles.
Other types of Antivirus agent
Fuzen Blocks the virus and cellular membrane fusion step involved in entry HIV into cells.
Amantadine and Rimantadine: specifically inhibit Influenza A virus by blocking viral
Section II - Virology By Dr. Kareem Lilo
Interferon are small proteins released by macrophages, lymphocytes, and tissue cells infected
When a tissue cell is infected by a virus it release Interferon, Interferon will diffuse to
surrounded cells. When it binds to a receptor on the surface of these adjacent cell they begun
the production of proteins that prevents the spread of the virus through the body .
Three types of interferon: alpha, beta and gamma:
A vaccine is a biological preparation that provides active acquired immunity to a
particular disease. A vaccine typically contains an agent that resembles a disease-causing
microorganism and is often made from weakened or killed forms of the microbe,
1. Attenuated live viral vaccines
These attenuated viruses can infect and replicate in the recipient and produce a protective
immune response without causing disease. Live attenuated viral vaccines can often confer
(Figure 2-5) Virus replication cycle
Section II - Virology By Dr. Kareem Lilo
lifelong immunity after one immunization series (e.g. : Measles vaccine ,Rubella vaccine Oral
2. Killed (inactivated) viral vaccines
Killed viral vaccines contain either whole virus particles, inactivated by chemical or physical
means, or some component(s) of the virus. They do not generally produce lifelong immunity
following one immunization series (e.g.: Rabies vaccine, Injectable poliomyelitis vaccine
3. Recombinant-produced antigens
Application of a recombinant DNA strategy to develop new vaccines. This approach has made
possible a safe and effective recombinant vaccine against hepatitis B virus, which has
replaced the vaccine derived from the plasma of hepatitis B virus-infected individuals.
Section II - Virology By Dr. Kareem Lilo
Diagnostic Methods in Virology
2. Indirect Examination (Virus Isolation)
1. Antigen Detection immunofluorescence, ELISA etc.
2. Electron Microscopy morphology of virus particles
3. Light Microscopy histological appearance
4. Viral Genome Detection hybridization with specific
nucleic acid probes polymerase chain reaction (PCR)
1.Cell Culture cytopathic effect (CPE)
Methods for Cultivation of Virus: (Figure 2-6)
Generally three methods are employed for the virus cultivation
1. Inoculation of virus into animals
2. Inoculation of virus into embryonated eggs ( Figure 2-7)
Figure 2-6 Method for cultivation of virus
Section II - Virology By Dr. Kareem Lilo
Laminar vertical flow hoods Contains HEPA filter Removes 99.97% of particles of 0.3μM
Figure2-8 laminar vertical flow hoadis
Figure 2-7 Inoculation of virus into embryonated eggs
Section II - Virology By Dr. Kareem Lilo
Cell Cultures are most widely used for virus isolation, there are 3 types of cell cultures:
1. Primary cells - Monkey Kidney
2. Semi-continuous cells - Human embryonic kidney and skin fibroblasts
3. Continuous cells - HeLa, Vero, Hep2, LLC-MK2, MDCK
Primary cell culture are widely acknowledged as the best cell culture systems available since
they support the widest range of viruses. However, they are very expensive and it is often
difficult to obtain a reliable supply. Continuous cells are the most easy to handle but the
range of viruses supported is often limited.
Cell culture Cytopathic Effect :
• Some viruses kill the cells in which they replicate, and infected cells may eventually
detach from the cell culture plate.
• As more cells are infected, the changes become visible and are called cytopathic effects.(
Figure 2-9 cell culture cytopathic effects
Section II - Virology By Dr. Kareem Lilo
Examples of Cytopathic Effects of Viral Infection
• Nuclear shrinking (pyknosis) • Margination and breaking of chromosomes
• Proliferation of nuclear membrane • Rounding up and detachment of cultured cells
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