VIRUSES

A virus is an infective agent that typically consists of a nucleic acid molecule in a protein
coat, is too small to be seen by light microscopy, and is able to multiply only within the living
cells of a host. They usually range in size from 16 to over 300 nm. The term or word virus
means poison and was originally used to describe pathogenic agents about which very little is
known. Following the discovery that contain pathogenic agents can pass through bacterial
filters by Ivanovsky in 1892. The word virus was applied to these agents and they were
referred to as filtrable viruses. Viruses are found in almost every ecosystem on Earth and are
the most abundant biological entity. Viruses infect all life forms-plants, animals and
microorganisms (including bacteria and archaea).

Viruses are described as not true cells because it combines some properties or characteristics
of living things with some of non-living things or matter. Some biologists have described it as
a transitional state between living and non-living matter-a cell precursor.

The characteristics that viruses possess include:

1. Viruses can multiply

2. Viruses contain specific nucleic acid (DNA or RNA)

3. The viral nucleic acid undergoes mutation and genetic recombination

The non-living matter or non-cell-like characteristics include:

 Viruses do not grow and are incapable of metabolism

 Viruses cannot multiply outside a living cell

 Viruses behave like standard chemicals. That is, they can be isolated, purified, and
crystallized and yet retain its biological properties.

STRUCTURE OF VIRUS

The virus is a nucleo-protein particle. That is, it is made up of two components, namely
nucleic acid and protein. The nucleic acid which may be DNA or RNA, is the hereditary
material and is found in the core. The core is surrounded by a protein coat called capsid.
Thus, a virus particle can be described as nucleocapsid. The nucleocapsid can either be naked
or enclosed by a membrane. A virus particle is also known as a virion. Tobacco mosaic virus,
papilloma virus and adenoviruses are examples of naked viruses. Influenza virus, herpes virus
and human immunodeficiency virus (HIV) are examples of enveloped viruses.

The Capsid: The capsid is made up of subunits called capsomeres. In most cases the
capsomeres are symmetrical. The symmetrical groups are:

- Cubic symmetry group

- Helical or screw-axis symmetry group

- Combined or complex symmetry groups

1. Cubic Symmetry: Cubic in this sense means a solid surrounded by a number of equal
faces. Most viruses that appear spherical are actually polyhedral. The preferred
polyhedral form is Icosahedron (20 faces-20 equilateral triangles and 12 vertices).

Fig: Adenovirus (with 10 faces of the back)

Adenovirus is a naked virus with cubic symmetry and is DNA virus. It is 700-750 Å
in diameter. The core nucleic acid is DNA with a molecular weight of 10×106
daltons(Da). Herpes virus is an example of cubic symmetry.

2. Helical or Screw-axis Symmetry: Tobacco mosaic virus (TMV) is a naked virus

with helical symmetry. Superficially, it appears as a rod, but the cylinder is threaded
atomically like a helix. The dimensions of TMV are 3000Å in length and 170Å in
width or diameter. It has an RNA nucleic acid of 2.2 x 106 daltons molecular weight.
It has 2100 to 2130 capsomeres per particle. Each capsomere is a polypeptide chain
consisting of 158 or 168 amino acids.

Influenza virus is an example of enveloped virus with helical structure.

 Fig: Tobacco mosaic virus

3. Complex or Combined Symmetry: Those viruses possess a structure which is

neither purely helical nor purely icosahedral, and they may possess extra structures
such as protein tail or a complex outer wall. Some bacteriophages have a complex
structure consisting of an icosahedral head bound to a helical tail. They may have a
hexagonal base plate with protruding protein tail fibers attached to it. Such structures
act like molecular syringes attaching to the bacterial host and then injecting the viral
genome into the cell.

Fig: Bacteriophage
Satellite Viruses

Satellite viruses or virusoids are small RNA or DNA molecules that code for one or two
proteins with which they are associated. Their replication and spread is dependent on another
virus being present in the same host cell as them. Virusoids are usually found together with
plant viruses. In humans hepatitis D is a virusoid that requires Hepatitis B in the same cell
with it to be able to proliferate.

Viroids are plant pathogens that consist of a circular RNA that does not code for proteins and
exhibits a complex two-dimensional structure. These infectious RNA molecules during
replication by RNA polymerase give rise to transitory secondary structures called
hammerhead because of their forms. They have RNase activity and autocatalytically cleave
the concatemeric RNA strands that result after replication. Ribozymes, small RNA species
with sequence-specific RNase activity are derived from the hammerhead-like RNA
structures.

Mimi viruses are a family of large DNA viruses which were discovered in 2004 in the
amoeba Acanthamoeba polyphaga by Didier Raoult. They are as large as bacteria hence the
name Mimivirus short for an abbreviation for Mimicking viruses. Another group of viruses
that are large than Mimiviruses have also been discovered in amoeba. They are referred to as
Mamaviruses.

These Mamaviruses can, themselves, be infected by smaller viruses called Virophages. They
are also referred to as Sputnik viruses. Virophages can only multiply in amoeba if the amoeba
is concurrently infected with a Mamavirus. The Virophage not only uses the Mamavirus as a
helper virus to replicate, but also inhibits the Mamavirus from replication or multiplication.

EFFECT OF VIRAL REPLICATION ON HOST CELL

When viruses replicate in a host cell, they integrate their genome into that of the host cell and
use the host cell machinery to produce copies of itself. These copies then leave the host cell
to infect other nearby cells. Once they leave the host cell, any of the following happens to the
host cell, depending on the type of virus:

 The host cell is destroyed and dies (lytic viruses)

 The host cell survives, becomes chronically infected and continuously produces small
numbers of the virus

 The cell survives and the viral genome remains in a latent state without producing
infectious particles (lysogeny)

 The host cell is immortalized, thus gaining the capability of unlimited cell division, a
process that can be associated with malignant transformation into a tumour cell.
CLASSIFICATION OF VIRUSES

Classification seeks to describe the diversity of viruses by naming and grouping them on the
basis of similarities. Lwoff et al. (1962) were the first to develop a means of virus
classification based on Linnaean Hierarchical system. Current virus classification is done by
the International Committee for Taxonomy of Viruses. Below are some of the criteria for
classification:

1. The nature of the genome (DNA or RNA) and the form in which it is present, that is,
is it Single or double stranded, in positive or negative sense, linear or circular,
segmented or continuous. Also, the arrangement of the genes or the nucleic acid is
important for the definition of individual species.

2. The symmetry form of the capsid.

3. The presence or absence of an envelope

4. The size of the virion.

5. The site of viral replication within the cell (cytoplasm or nucleus).

The further subdivision into genus and virus group is largely based on serological criteria and
the similarity of genome sequences.

BACTERIOPHAGES

The word Bacteriophage consists of two words - bacteria and phage. The word phage in Latin
means to devour. Hence Bacteriophage means a virus that devours or kills bacteria.
Bacteriophages are ubiquitous viruses found whenever bacteria exist. It is estimated that 10 31
bacteriophages are on planet Earth.

Bacteriophage or Simply phage, is any group of viruses that infect bacteria. Bacteriophages
also infect the single-celled prokaryotic organisms known as archaea. Bacteriophages are
composed of proteins that encapsulate a DNA or RNA genome and may have structures that
are simple or elaborate.

There are three basic structured forms of phages: an icosahedral head with a tail, an
icosahedral head without a tail, and a filamentous form. Phages are classified based on
morphology and nucleic acid content. They are classified in a number of virus families and
include Inoviridae, Microviridae, Rudiviridae, Tectiviridae, etc.

Phages replicate mainly by either lytic or lysogenic means. Other modes of replication are
also encountered. It is important to note that those phages are specific in bacteriophage
activity. That is, not all phages infect all bacteria. Specific phages infect specific bacteria. A
phage must attach to specific sites on the cell wall of bacteria.
USES OF BACTERIOPHAGE

1. To treat antimicrobial infections, especially those caused by multi-drug resistant

isolates or bacteria

2. To prevent food spoilage

3. To produce therapeutic antibodies to treat diseases

4. Phage is used in diagnosis. For example, the TB test for tuberculosis used
bacteriophage to detect tuberculosis bacteria

5. For epidemiological surveillance and to determine bacteria strain

6. For counteracting exotoxins and toxins

7. To prevent plants and vegetables from decay and spread bacterial disease

8. As biocides for antimicrobial surfaces, e.g., hospitals, and as pre-treatment for

catheters and medical devices before use in clinical settings

9. Antimicrobial drug discovery

10. Use in basic research

INFECTION

The term infection is defined as the successful establishment and growth of microorganisms
in the tissues of the host. From the definition of infection, it follows that microorganisms will
first invade the host. The host has local defenses to prevent bacterial or microbial invasion
and maybe stop infection. It is only when the microorganism is able to overcome the host
defenses and multiply in the host tissues that infection takes place. However, certain factors
in the microorganism will determine whether a microorganism can initiate infection. Before
we go further, let’s define certain terminologies used in infectious diseases.

 Avirulent - refers to microorganisms that lack the ability to cause disease.

 Colonization - refers to the establishment of microbial growth on a surface (usually

host).

 Disease - refers to a noticeable impairment of body function.

 Infectious disease - refers to any condition in which there is a noticeable impairment

of body function caused by microorganisms.

 Pathogen - refers to any disease-causing microorganism.

  Pathogenicity - refers to the ability to cause disease.

 Pathogenesis - refers to the origin and development of disease.

 Virulence - refers to the enhanced disease-producing capabilities of microorganisms.

CAUSES OF INFECTIOUS DISEASES

In the 19th century, it was difficult to prove that microorganisms were the cause of infections.
It was Robert Koch (1876) who reported his observations with anthrax (caused by Bacillus
anthracis) that showed that microorganisms were responsible for infections. His observations
form the basis of what is referred to as Koch’s postulate or germ theory of disease. Koch’s
postulate is simply:

 That the causative microbe is found in the body in all cases of the disease.

 That the microbe can be isolated in series of pure cultures in vitro.

 That inoculation of the pure culture into susceptible experimental animals will
reproduce the disease.

 The microbe will be re-isolated in pure cultures from the experimental animal.

If carefully obeyed and followed, these simple rules provide a logical basis for concluding
that an organism produces a given disease. However, there are conditions where all four rules
cannot be observed. That is, some microorganisms do not meet the above criteria to show or
confirm that a microorganism caused a disease. For example, Mycobacterium leprae, the
aetiological agent of leprosy, cannot be grown or cultivated in vitro. Another example is
Neisseria gonorrhoeae, the aetiological agent of gonorrhea, does not produce disease in
animals. Also, apparently healthy individuals may be carriers of pathogenic microorganisms.
A carrier is a person who harbors the microorganism that can cause a particular disease
without experiencing symptoms of infection and who can transmit the microorganism to
others.

Microbial genetics has led to the study of non-pathogenic and pathogenic bacteria, but absent
in non-pathogenic bacteria. The molecular Koch’s postulate is referred to as molecular
Koch’s postulate. The molecular Koch’s postulate states that:

 The phenotype or property under investigation should be associated with a pathogen’s

virulence.

 Inactivation of the gene(s) associated with the virulence should result in a measurable
decrease in virulence.

 Introduction of a cloned virulence gene into a non-pathogenic strain should convert

the strain to a pathogenic strain.
If these criteria are met, it can be concluded that the gene is essential for virulence.

STEPS IN INFECTIOUS PROCESS

A microorganism that can cause infection should be able to complete the following steps:

1. Attachment and/or entry into the host.

2. Local or general spread in the body.

3. Multiply.

4. Evade host defenses.

5. Cause damage to the host (not necessary, but often occurs).

6. Exit the host.

7. Able to survive outside the host.

As mentioned earlier, certain factors on both microorganisms and host will determine if a
microorganism can cause infection. Microbial factors include:

 Specificity: Some microorganisms are only able to cause infection in certain hosts.
For example, Neisseria gonorrhoeae only causes infection in man and consist of a few
organisms that can cause infection in animals. However, there are few organisms that
can cause infection in both humans and animals (Bacillus anthracis).

Types of Microorganisms

Some microorganisms are referred to as true pathogens while others are non-pathogenic or
opportunistic pathogens. True pathogens possess properties that enable them to overcome the
host defenses and infect the host. Those characteristics include transmissibility, adherence to
host cells, invasion of host cells and tissues, toxigenicity, and ability to evade the host
immune system.

1. Opportunistic pathogens: These are commensal microorganisms which constitute

the normal flora of the host and do not normally cause disease in the host because of
their inability to overcome the host defenses. Hence, they may be regarded as non-
pathogenic. However, these organisms may become pathogenic if they leave their
natural habitat and gain access to other parts of the body. For example, Escherichia
coli is a normal flora of the gut, but is a pathogen in the urinary tract. Also, conditions
that render the host immunocompromised or immunosuppressed (such as another
disease condition or taking certain drugs) allows these microorganisms to become
pathogenic. For example, AIDS, immunosuppressive therapy as in cancer cases, etc.
Opportunistic infections can also arise by taking antibiotics that eliminate normal
 flora (bacteria) but allows other microorganisms (fungi) to overgrow and cause
infection.

2. Adherence: The invading pathogen must be able to adhere to the host tissue or cells
or tissues otherwise, it will be swept away by mucus or other fluids that bathe the
cells or tissues. Pili (fimbriae) are organelles used by bacteria for attachment.

3. Virulence: Following adhesion is virulence of microorganisms. Virulence is a

complex property which depends, among other factors, on invasiveness and
toxigenicity. Invasiveness is the ability of microorganisms to penetrate the tissues,
overcome host defenses, multiply and disseminate widely. Toxigenicity is the ability
of a microorganism to produce toxins that contribute to the development of disease.
Bacterial toxins are generally classified as exotoxins and endotoxins.

“Virulence may also depend on the number of organisms as well as the phase of
growth”. Generally, large numbers of microorganisms deposited in tissues are more
likely to establish an infection than a few numbers. However, there are few
exceptions, for example, enteropathogenic Escherichia coli requires 10-100 colony-
forming units to cause infection. Bacteria in the log or exponential phase of growth
are more likely to cause infection than those in the stationary phase.

Host Association (type of association):

This entails the association between microorganisms and the host and the environment they
make to the host.

1. Saprophytism: These are free-living microorganisms which obtain their food and
nutrients from dead and decaying animal and plant tissue as well as soil and water.
They do not require living host and only in rare cases do they cause disease.

2. Parasitism: These organisms adapt their life on or in the bodies of higher organisms.
The association may take any of the following forms:

3. Commensalism: Ability to live on the external or internal surfaces of the body

without causing disease. Commensal organisms form the normal flora in man. Some
commensal organisms can become pathogenic (opportunistic pathogens).

4. Mutualism: Both the microorganism and the host benefit from the association.

5. Parasitism: The microorganism benefits at the expense of the host. This may cause
disease in the host.

6. Parasitism: Organisms that obtain food or nutrients and shelter from the host (or
another organism). Pathogenic microorganisms are found in this group (true
pathogens).

7. Symbiosis: Relationship between two or more organisms in which the participants are
of mutual benefit to one another.
Host factors: Various factors affecting an individual or a community contribute to the
occurrence of infection. The very young and elderly are more susceptible to infection as well
as the malnourished. Gender also plays a major role in infection as some organisms are more
likely to cause infection with a specific role for example, urinary tract infection caused by
Escherichia coli is more prevalent in females than males. The portal of entry and the body
environment plays a major role. For example, organisms that are acid sensitive are less likely
to cause infection in acidic parts of the body. That is to say that the organism should meet
with suitable conditions in the tissues to establish an infection. Some of these conditions
include nutritional factors, pH, temperature, oxidation-reduction potential, etc.

Other host factors include metabolic disorders such as diabetes mellitus, consequence of
surgery, antecedent disease that lowers resistance to infection. Use of broad-spectrum
antibiotics with consequent elimination or suppression of normal flora, use of sutures,
indwelling bladder catheters, tracheostomy tubes, and cardiovascular prostheses,
considerably increase the risk of infection.

Among community factors that may affect host resistance are the complex components of
poverty (overcrowding, inadequate food, clothing, and housing, poor personal hygiene,
immigration, and population movements including those in tourist camps; drug addiction and
alcoholism, and large-scale disasters (earthquakes, hurricanes, floods, etc.).

RESISTANCE TO INFECTION

For an infection to occur, the pathogen must overcome the host defense. The host defense is
what the host has to resist infection. Humans have two defenses against microbial invasion,
namely: innate (non-specific) or natural immunity and adaptive (specific) or acquired
immunity.

The innate or natural immunity is termed non-specific because they are active against a
variety of microorganisms, and they include the following:

 Physical barriers

 Antimicrobial activity of the normal commensal flora

 Microbicidal substances present in body fluid and secretions

 Microbicidal substances liberated from host cells and tissues damaged during the
infective process

 Phagocytosis by macrophages (polymorphonuclear leucocytes) and macrophages

(fixed reticulo-endothelial system and wandering monocytes)
Innate immunity can be defined as immunity that is not affected by prior contact with the
etiological agent. In other words, innate immunity operates constantly to prevent
establishment of infection against all of the specific defenses.

Acquired immunity is the last line of defense against invading microbes. The response is
termed specific because it is directed against the invading agent only. In other words, it is
directed against the microbe that caused the infection.

The adaptive immune system is composed of two major components:

 Humoral immunity

 Cellular immunity

Humoral immunity is mediated by B-lymphocytes and is characterized by the production of

antibodies. Antibodies are proteins that bind to specific antigens on the surface of the
pathogen. This binding can lead to the destruction of the pathogen or can make it easier for
other cells of the immune system to destroy it.

Cellular immunity is mediated by T-lymphocytes. T-lymphocytes can kill infected cells

directly or can release cytokines that help to activate other cells of the immune system.

Specific immune response has the following fundamental features

1- The response is highly specific

2- The response has memory in that once the host has responded to a specific antigen, a
subsequent exposure to the same antigen is more rapid and effective, thereby quickly
eliminating that antigen

3- The response involves two sets of lymphocytes - the B and T lymphocytes, acting together
with macrophages, and it may be predominantly an antibody (B cell) response or a cellular (T
cell) immune response

NB ==> Individual immunity may be acquired naturally or artificially, and both forms may
be acquired either actively or passively.

1. Active immunity:

 Natural: Occurs when an individual is exposed to a pathogen and develops specific

antibodies in response. This is a slow process, taking days to weeks after the onset of
disease. This is actively acquired immunity since the antibodies are produced by the
host’s cells or tissues.

 Artificial: Can be induced artificially by injecting killed whole bacteria into the body
to elicit antibody production or by injecting a bacterial toxin (toxoid) which produces
 antitoxin which protects the individual on subsequent exposure - for example, the
injection of tetanus toxoid to protect the individual against tetanus.

2. Passive immunity:

In passive immunity, the host has no part in the production of the antibody. Most
infants are resistant to certain specific infections during the first 4 to 6 months of life.
This immunity is due to the antibodies transferred from mother to offspring through
the placenta or through breast milk. This is naturally acquired passive immunity.

On the other hand, a patient suspected of having tetanus is treated with an injection of
tetanus antitoxin. This is called artificial passive immunity.

In the case of actively acquired immunity, the resistance gained is retained by the body for a
long time. Some actively acquired immunity can last for upwards of 10 years. But in the case
of passively acquired immunity, the protection is short-lived. This period is limited to 6
months, and not more than that. This is the time it takes the given antibodies to be eliminated
by the body. Since the body was not trained in producing the antibody, no further antibody
emerges when the ones given passively are eliminated, and so no protection is given to the
host on subsequent exposure to the same pathogen.

SOURCES OF INFECTION

Microorganisms capable of causing disease in humans are derived from various sources:

1. Humans (the most important source)

2. Animals (much less important)

3. Inanimate objects (relatively important)

These sources of infection can be divided into:

 Exogenous Sources: Sources outside the patient, including humans, animals, and
inanimate objects.

 Humans
Endogenous Sources : Sources within or on the patient. Humans
Animals  Patient

Exogenous Inanimate Endogenous  Carrier

e

TRANSMISSION OF INFECTIONS

There are five ways in which infections are transmitted from one person to another:
  Direct contact: (e.g., touching)

 Contact with fomites: (e.g., clothing, household articles)

 Through the air

 Transplacental

 Ingestion

Depending on the site, more than one mechanism of spread may be involved.

ANTIMICROBIAL AGENTS

An antimicrobial agent is defined as any substance, natural, semi-synthetic or synthetic that

kills or inhibits the growth of microorganisms. Antimicrobial agents can be grouped based on
the microorganisms they act primarily against. For example, those that act against bacteria
are referred to as antibacterial agents, those against fungi, antifungal agents, those against
viruses, antiviral agents, and those against parasites, antiparasitic agents.

Some antimicrobial agents are referred to as antibiotics.

An antibiotic is a chemical substance produced by microorganisms of microscopic plants

which has the ability to kill or inhibit the growth of other microorganisms when used at low
concentrations. A chemical substance that performs the same function but is chemically
synthesized (not of microbial origin) is called a chemotherapeutic agent. Disinfectants are
chemicals used to kill or reduce microbial load on inanimate objects. Antiseptics are
chemicals applied topically (skin) to kill microorganisms. If the action of an antimicrobial
agent results in the death of microorganisms, the agent is said to have a cidal activity; while if
it only inhibits the growth of the organism, it is said to have a static activity.