Download College of Medicine Microbiology

College of Medicine
Microbiology
Medical Virology
Viral infection and pathogenesis:
Dr. Jawad Kadhim Tarrad
-------------------------------------------------------------------------------------------Infection is presence and multiplication of pathogenic microbe within
human body, and cause symptoms of infection. The infection differs from
other diseases is that caused by living microbial pathogens.
The disease is impairment of normal state of organism or any of its
components that hinders the performance of vital functions. It is occurring
due to malnutrition, physiologic disorder, inherent defect of body ,climate
and industrial hazard, specific infectious agents, or combination of these.
The disease term include infectious diseases and non-infectious diseases.
The viral pathogenesis refers to ability of viruses to cause infections in
human.
Stages of viral infection:
 Transmission of virus from external source to host body through the
portals of entry.
 Adhere to and /or invade susceptible host tissues.
 Multiply and spread to adjacent cells or to specific cells.
 Evasion of host defense mechanism.
 Damage the host tissues and disease symptoms.
 Progression or resolution of the disease.
 Shedding of virus in some instances.
Main sources of infection:
1. Human: the common sources of infection are patients or carriers. The
carrier is person recovered from disease but harboring virus in his
body. Fomites are inanimate objects of patients that may be
contaminated and serves as source of infection.
2. Animals: The infected animals can be serve either the source
(reservoir) or made transmission (vector)of certain viruses as in
arthropod-borne infection .
3. Food: the foods are most important media for transporting the viruses
to human during consumption of contaminated food, and therefore act
as food-borne infection.
1
4. Water: many viruses may be found in water. The infectious agents
are transmitted to human by consumption of water or when swimming
in it, therefore act as water-borne infection.
Transmission and Portals of entry:
Portals of entry(routes of infection) :
Major:
Minor:
1. Respiratory tract(nose).
1. Eye.
2. Elementary tract(mouth).
2. Anus.
3. Skin, non-intact.
3. Ear canal
4. Genital tract(vagina).
4. Urethral canal.
Modes of transmission:
 Most viral infections are communicable capable of spreading from
person to person. If a disease is highly communicable ,the term
contagious is applied.
 The infectious agent is transmitted from source of infection to human
either by vector (entity living such as insects, ticks and mite), or by
vehicles (entity non-living such as fomites, water, food, air, medical
devices and other inanimate objects).
 The infection is occurring or acquired from hospital, called hospitalacquired infection( nosocomial infection) . The infection obtained
from outside the hospital among human community, called
community-acquired infection. The subsequent infection by same
organism in same patient is called re-infection.
Horizontal transmission :
 Inhalation : the pathogenic agents may be transmitted by inhalation
of respiratory secretions(air droplet nuclei containing infectious
agents) of infected patients, or by inhalation of contaminated dust (air
borne) with virus .
 Ingestion: the infectious agents can be transmitted by consumption
(during eating or drinking) of contaminated water or food.
 Skin : any small break, abrasion, and wound in skin that permit initial
entry. The transmission may occur through direct contact(such as
handshaking, kissing)with infected person , infected animal or during
handling of fomites of patients, or the organism is transmitted
indirectly by vector bite .
2
 Blood transfusion: some pathogenic microorganisms can be
transmitted by blood transfusion. Injection of needles during
intravenous drug use or indwelling catheter, have role in transmission.
 Sexual intercourse: certain pathogenic microorganisms can be
transmitted by sexual contact in homosexual or heterosexual persons.
Vertical transmission:
The pathogen can transmit from infected mother to her fetus;
 across the placenta (prenatal) ,or
 at time of delivery from birth canal (perinatal), or
 during breast feeding(postnatal) .
Adherence of virus to target cell:
The viruses tend to exhibit cell and organ specificities (cell tropism ). The
viral affinity for specific body tissue is dependent on :
1. Presence of specific cellular receptors on cell surface which
interact with virus, and initial infection.
2. Ability of host cell to support viral replication such as Physical
barriers, local temperature, pH, oxygen tension and nutrients are
very important in tissue tropism.
Invasion of host tissues(replication and dissemination):
 The viruses replicate and produce diseases at site of entry or at site
distant from their point of entry. In other word, the viral infections are
either localized on the portal of entry or spread systemically through
the body.
 After primary replicate at site of entry , then the virus spread within
body of the host from local replication to target cells . Mechanism of
viral spread vary, the most common route is via blood stream,
lymphatics or nerves. The presence of virus in blood stream is called
viremia.
Evasion of host defenses:
The viruses when meet the host cell faced several antimicrobial defenses
of host. The viruses have many mechanisms to avoid action of host
defenses:
 Certain viruses encode some proteins act as receptors for immune
mediators such as interferon (IFN) and tumor–necrosis factor (TNF).
When the virus released from virus-infected cell , these proteins bind
to immune mediators and block their ability to interact with receptor
3




on their intended target. Because reducing host defense, the virulence
of virus is enhanced. These virus-encoded proteins that block host
immune mediators are called cytokines decoys.
Certain viruses have multiple antigenic types (multiple serotypes).
The patient can be infected with one serotype , recover , and have
antibodies that protect from infection by that serotype in future ,
however , that person can be infected by other serotypes of virus.
Most viruses have one serotype , but certain have several serotypes
such as rhinovirus which has more than 100 serotypes , this is the
reason why the common cold by this virus is common.
Antigenic variation may occur in certain viruses such influenza virus.
Certain viruses are able to thwart immune defenses for numbers of
reasons such as latent or can infect cell for long period without
adverse effects on cell.
Certain viruses are spread from cell to cell without exposed to
immune system. They don’t form extracellular phase.
Damage of host cell(pathogenesis) :
The time between exposure to virus and onset of disease is called
incubation period, it required to produce sufficient numbers of virus that
lead to cause disease. This period reflects the time needed for the infectious
agents to overcome early defense and grow to a population size.
The mechanisms of viral diseases are various:
1. Most viral diseases are result in host cell death by several
mechanisms:
 Shutoff macromolecules synthesis, or by
 Lyses of the cell membrane by lysozymes during viral replication,
or by
 Induction of programmed cell death (suicide program, apoptosis)
by some viruses (eg: HIV).
2. The pathogenesis may result from immunological attack: for example,
 The hepatitis viruses don’t cause a cytopathic effect in liver cells ,
but the damage of hepatocytes is result of recognition of viral
antigens on hepatocyte surface by cytotoxic T-cell.
 Some viruses stimulate cellular cytokines that play important role in
immunopathogenesis .For example, diarrhea caused by rotavirus, the
rotavirus-infected cells produce cytokines that stimulate the enteric
4
neuron, resulting in excess fluid and electrolytes secretion into the
bowel lumen.
 Damage caused by immune response of host to infection, the
response is often which leading to harmful outcome for host such as
hypersensitivity and autoimmune.
Outcome of infection:
 If the host defenses overcome the virulent virus in first step, the
disease is not occurring.
 If viral pathogens overcome the defenses of infected individual, the
disease resulted and it may progress to cause death of infected host.
 If the host defenses overcome the virulent microbe after infection, this
lead to repair and healing, and recovery from infection.
 If the host defense is failure to eliminate the microbe from the body,
the infection may become chronic(persistent infection), which mean
the microbes may continues to multiple and produce significant
symptoms of disease for long period.
Persistent viral infection:
 Three types of persistent viral infections:
1. Chronic infection: certain patients who have infected with
some viruses continue to produce significant symptoms of
disease and significant amount of virus for long period.
2. Latent infection: certain patients recover from initial infection
and virus production stops. But the patients harboring the virus
in their bodies (remain as carriers) without produce symptoms.
3. Slow virus infections: some infections require to long period
between initial infection and onset of disease, which are usually
measured in years (such as Kuru disease, and HIV).
 The mechanisms that may play a role in persistence of viral infections
include:
1. Integration of provirus into chromosome of host cell without viral
replication, as occur in retroviruses.
2. Spread from cell to cell without extracellular phase , so that is not
exposed to immune response .
3. Occurrence of rapid antigenic variation in some viruses .
4. Location of virus within immunological sheltered e.g. : brain.
5
5. Immune tolerance may occur in some patients, because
neutralizing antibodies are not formed.
6. Some patients suffer from immunosuppression , as in AIDS.
Virus shedding:
The last stage in pathogenesis is the shedding of infectious virus into
environment. The shedding usually occurs from the body surface
involved in viral entry. The shedding occurs at different stages of
disease dependent on particular agent involved.
Predisposing factors of infection:
The infection does not arise in vacuum. It results from interaction of
several factors. The risk factors that involved in the development of
infections include mainly three factors:
 Microbial factors: virulent microbe should be having virulence
factors (such as: adherence factors, invasive factors, factors mediating
avoid host defenses and factors cause damage the tissue of infected
host).
 Host factors: susceptible host is complaining from; defect or suppress
in immune system, disorder in physiologic state and hormones,
pregnancy, stress , malnutrition, age and race, and others.
 Environmental factors: Climate and seasonal variations, activities of
some microbes and vectors are increased.
 Lifestyle, social and behavior changes, economic and hygiene status,
foreign bodies (indwelling devices), housing and crowding, all these
facilitate infection.
6