MEDICAL VIROLOGY

Faiza Rashid (Lecturer)

Microbiology (4th Semester)
COBAM
 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 nucleic acid.
This is composed of repeating protein 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 human pathogen
example. It requires the presence of hepatitis B virus to complete its replication
cycle.
• C. 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 infectious protein molecules
that contain no definable nucleic acid and are responsible for the
transmissible and familial encephalopathies. A prion is a type of
protein that can trigger normal proteins in the brain to fold abnormally.
Prion diseases can affect both humans and animals and are sometimes
spread to humans by infected meat products. The most common form
of prion disease that affects humans is Creutzfeldt-Jakob disease (CJD).
 Discovery
• Viruses were first discovered after the development of a porcelain filter—
the Chamberland-Pasteur filter—that could remove all bacteria visible in the
microscope from any liquid sample.
• In 1886, Adolph Meyer demonstrated that a disease of tobacco plants—
tobacco mosaic disease—could be transferred from a diseased plant to a
healthy one via liquid plant extracts.
• In 1892, Dmitri Ivanowski showed that this disease could be transmitted in
this way even after the Chamberland-Pasteur filter had removed all viable
bacteria from the extract. Still, it was many years before it was proved that
these “filterable” infectious agents were not simply very small bacteria but
were a new type of very small, disease-causing particle.
 Viruses
• Viruses are non-cellular, microscopic infectious agents that can only replicate inside a
host cell. From a biological perspective, viruses cannot be classified either a living
organism or non-living. This is due to the fact that they possess certain defining
characteristic features of living organisms and non-living entities.
• A virus is a non-cellular, infectious entity made up of genetic material and protein that
can invade and reproduce only within the living cells of bacteria, plants and animals.
• A virus cannot replicate itself outside the host cell. This is because viruses lack the
required cellular machinery. Therefore, it enters and attaches itself to a specific host cell,
injects its genetic material, reproduces by using the host genetic material and finally the
host cell splits open, releasing the new viruses.
• Viruses can also be crystallized, which no other living organisms can do. It is these
factors that lead to viruses being classified in the grey area – between the living and non-
living.
 Viral Morphology
• Viruses are noncellular, meaning they are biological entities that do not have a cellular
structure.
• They therefore lack most of the components of cells, such as organelles, ribosomes, and the
plasma membrane.
• Viruses are tiny and smaller in its size, ranging between 30-50 nm. They usually lack a cell
wall but are surrounded by a protective protein coating called the capsid.
• A virion consists of a nucleic acid core, an outer protein coating or capsid, and sometimes an
outer envelope made of protein and phospholipid membranes derived from the host cell.
• Viruses may also contain additional proteins, such as enzymes, within the capsid or attached to
the viral genome.
• Viruses come in many shapes and sizes, but these features are consistent for each viral family.
• The viral genome is packed in a capsulated symmetric protein. The protein associated with
nucleic acid (also known as nucleoprotein) produces the nucleocapsid with the genome.The
proteins of the capsid are encoded in the viral genome, and are called capsomeres. Some viral
capsids are simple whereas others are quite complex in structure
 Classification
• Modern classification is based on the following three characteristics:

A. Type of viral nucleic acid (RNA or DNA, single-stranded or

doublestranded) and its replication strategy.

B. Capsid symmetry (icosahedral or helical).

C. Presence or absence of lipid envelope.

 Classification based on the presence of
nucleic acid
• Unlike nearly all living organisms that use DNA as their genetic material, viruses may use either DNA or RNA.
Viral genomes tend to be small, containing only those genes that encode proteins which the virus cannot get
from the host cell. This genetic material may be single- or double-stranded. It may also be linear or circular.
• While most viruses contain a single nucleic acid, others have genomes divided into several segments. The RNA
genome of the influenza virus is segmented, which contributes to its variability and continuous evolution, and
explains why it is difficult to develop a vaccine against it.
• DNA virus :The virus, having DNA as its genetic material. There are two different types of DNA virus
• Single-stranded (ss) DNA virus: e.g. Picornaviruses, Parvovirus, etc.
• Double-stranded (ds) DNA virus: e.g. Adenovirus, Herpes virus, etc.
• RNA virus: The virus, having RNA as its genetic material. There are two different types of RNA virus
• Double-stranded (ds) RNA virus: e.g. Reovirus, etc.
• Single-stranded (ss) RNA virus. It is further classified into two Positive sense RNA (+RNA) and negative sense
RNA (-RNA). Poliovirus, Hepatitis A, Rabies virus, Influenza virus are examples of single-stranded RNA virus.
 Classification based on the presence
of nucleic acid
• In DNA viruses, the viral DNA directs the host cell’s replication proteins to synthesize new
copies of the viral genome and to transcribe and translate that genome into viral proteins.
ØHuman diseases caused by DNA viruses include chickenpox, hepatitis B, and adenoviruses.
Sexually transmitted DNA viruses include the herpes virus and the human papilloma virus
(HPV), which has been associated with cervical cancer and genital warts.

• RNA viruses contain only RNA as their genetic material. To replicate their genomes in the
host cell, the RNA viruses must encode their own enzymes that can replicate RNA into RNA
or, in the retroviruses, into DNA. These RNA polymerase enzymes are more likely to make
copying errors than DNA polymerases, and therefore often make mistakes during
transcription. For this reason, mutations in RNA viruses occur more frequently than in DNA
viruses. This causes them to change and adapt more rapidly to their host.
ØHuman diseases caused by RNA viruses include influenza, hepatitis C, measles, and rabies.
The HIV virus, which is sexually transmitted, is an RNA retrovirus.
Classification based on the
structure or symmetry
• Complex virus. E.g Poxvirus

• Radial symmetry virus. E.g.Bacteriophage

• Cubical or icosahedral symmetry shaped virus. E.g. Reovirus,

Picornavirus

• Rod or Spiral shaped or helical symmetry virus.E.g. Paramyxovirus,

orthomyxovirus
Classification based on the replication
properties and site of replication
• Here, viruses invade into the host cell, where it replicates and assembly within
the cell organelles.
ØReplication within the cytoplasm of the host cell. E.g. All RNA viruses except
the Influenza virus.
ØReplication within the nucleus and the cytoplasm of the host cell. E.g. Influenza
virus, Poxvirus, etc.
ØReplication within the nucleus of the host cell. All DNA viruses except Pox
virus.
ØReplication of the virus through the double-stranded DNA intermediate. E.g. All
DNA viruses, Retrovirus and some tumour causing RNA virus.
ØReplication of the virus through a single-stranded RNA intermediate. E.g. All
RNA viruses except Reovirus and tumour-causing RNA viruses.
Classification based on the host range
• Based on the type of host, there are four different types of viruses:
• Animal viruses
• These viruses infect by invading the cells of animals, including humans. Prominent examples of animal viruses
include the influenza virus, mumps virus, rabies virus, poliovirus, Herpes virus, etc.
• Plant viruses
• These viruses infect plants by invading the plant cells. Well-known examples of plant virus include the potato
virus, tobacco mosaic virus, beet yellow virus, and turnip yellow virus, cauliflower mosaic virus, etc.
• Bacteriophage
• The virus which infects bacterial cells is known as bacteriophage. There are many varieties of bacteriophages,
such as DNA virus, MV-11, λ phage, T4 bacteriophage (infects E.Coli) etc.
• Insect virus
• The virus which infects insects is known as Insect virus, also called the viral pathogen of insects. These viruses
are considered as a powerful biocontrol agent in the landscape of modern agriculture. Ascovirus virions and
Entomopox virus, are best examples for insect virus.
Classification based on the mode of
transmission
• Airborne infections – Transmission of the virus through the air into the
respiratory tract. E.g. Swine flu, and Rhinovirus.
• Fecal oral route – Transmission of the virus through the contaminated water
or food. E.g. Hepatitis A virus, Poliovirus, Rotavirus.
• Sexually transmitted diseases – Transmission of the virus through sexual
contacts with the infected person. E.g. Retrovirus, human papillomavirus, etc.
• Transfusion-transmitted infections- Transmission of the virus through the
blood transfusion. E.g. Hepatitis B virus, Human Immunodeficiency Virus, etc.
• Zoonoses -Transmission of the virus through the biting of infected animals,
birds, and insects to human. E.g. Rabies virus, Alpha virus, Flavivirus, Ebola
virus, etc.
 Pathogenesis of Viral Diseases
• A particular virus with the human host is dependent on both
pathogen and host factors. 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.
 Pathogenesis of Viral Diseases
• A generalized schema of viral infection leading to disease in the human host is as follows:
1. Depending upon the agent, the virus enters through the skin, mucous membranes,
respiratory tract, gastrointestinal tract, via a transfusion or transplanted organ or via maternal-
fetal transmission.
2. There is local replication at the site of the inoculation. Certain agents exhibit pathology at
the skin or mucous membrane surface – e.g., herpes simplex virus, human papillomavirus.
3. For some neurotropic viruses there may be spread along peripheral nerve routes to ganglia
(e.g., herpes simplex virus) or the central nervous system (e.g., rabies virus). For other
neurotropic agents, the central nervous system is seeded following viremia.
4. For many agents, there is replication in regional lymph nodes with subsequent viremia and
spread to target organs. Some viruses travel in the bloodstream free in plasma (e.g.,
picornaviruses); others are cell associated (e.g.,cytomegalovirus).
5. Replication in target organs may lead to local damage and further rounds of viremia.
6. Non-specific and specific host immune responses come into play to try to control and
downregulate the viral replicative process.
Immune Responses to Viral Infections
1.Non-specific immunity refers to those elements of the immune system that can
clear virus or virus infected cells immediately upon or shortly after viral exposure
and which are not dependent upon immunologic memory. Non-specific immunity
may include:
ØPhagocytic cells (neutrophils and monocyte/macrophages).
ØCytokines (e.g., interferons) and chemokines.
ØNatural killer cells.
ØPoorly defined antiviral factors that may exist in blood or body fluids.
2. Specific immunity refers to antigen specific B and T cell responses that lead to
the development of antibodies, cytotoxic T cells and antibody dependent
cellular cytotoxicity.
3. In some instances, an intense immunologic reaction to a viral agent can result
in immunopathology and a serious clinical syndrome. A prime example is dengue
hemorrhagic fever which is likely due to antibody dependent enhancement and T
cell activation on re-exposure to dengue virus.
Mechanisms of Viral Persistence
• 1.Viruses may cause chronic, persistent infection with continuous viral replication in the face
of an immune response. Examples include HIV, hepatitis B virus and hepatitis C virus.
• 2.Some viruses may demonstrate persistent infection in immune compromised hosts. These
include the herpesviruses, human papillomavirus and rubella virus.
• 3. Some viruses are able to cause latent infection. Latency is characterized by a quiescent or
minimally transcriptionally active viral genome with periods of reactivation. Latent viruses
include the herpesviruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus,
varicella-zoster virus), human papillomavirus, human retroviruses.
• 4. Sites of persistence include the nervous system (herpes simplex virus, varicella zoster virus,
measles virus, poliovirus, JC virus), the liver (hepatitis B virus, hepatitis C virus), and
leukocytes (HIV, cytomegalovirus, Epstein-Barr virus).
• 5. Oncogenesis : Several viruses are associated with human cancers. These include:
Epstein-Barr virus with lymphoma, nasopharyngeal carcinoma and leiomyosarcoma;
herpesvirus with B-cell lymphoma; hepatitis B and C viruses with hepatocellular carcinoma;
and human papillomavirus with cervical cancer. Mechanisms of oncogenesis can include
transformation and binding of tumor suppressor proteins
Diagnosis of Viral Infections
• The diagnosis of viral infections relies first on the recognition of a distinct clinical syndrome ) or a
consideration of the viral infection in the differential diagnosis of a presenting syndrome.
• The second consideration is the knowledge of the appropriate specimens to send to the laboratory
(blood, body fluids, lesion scraping, tissue) to diagnose a particular infection.
• A variety of methods exist to diagnose viral infections with the recent trend being toward molecular
diagnostics. These methods include:
• 1. Isolation of virus in tissue culture, animals, embryonated eggs. Most diagnostic laboratories only
use tissue culture for virus isolation.
• 2. Antigen detection in body fluids or blood or lesion scrapings.
• 3. PCR amplification and/or nucleic acid probes to detect viral nucleic acid in body fluids or tissues.
• 4. Antibody detection. IgM antibody detection can assist with acute diagnosis. Four-fold rises in IgG
specific antibody.
• 5. Examination of tissue samples by light microscopy.
• 6. Examination of body fluids or tissues by electron microscopy.
Prevention and Therapy
• Vaccines for the prevention of life threatening viral infections are one of the
most significant advances in human health. The eradication of smallpox is the
hallmark example of the effectiveness of a viral vaccine.
• Immune globulin can prevent or ameliorate clinical disease due to certain viral
agents. Examples include varicella-zoster immune globulin for exposure in
immune compromised hosts.
• Screening of blood for prevention of transmission of HIV, hepatitis B, hepatitis
C and in certain transplant situations, cytomegalovirus.
• Safe sexual practices for the prevention of HIV, hepatitis B and human
papillomavirus infections.
• Advances in specific antiviral therapy over the past 30 years have been marked.
Effective therapy exists for herpes simplex virus, varicella-zoster virus,
cytomegalovirus, HIV, influenza virus, respiratory syncytial virus, hepatitis B
and hepatitis C.