MEDICAL MICROBIOLOGY II

Lesson 7

Basic Virology Part II

Pathogenesis of Viral Infections

Pathogenesis - the study of how a disease
starts
Before a virus can cause an infection, it MUST:
Enter the host
Come into contact with susceptible cells
Overcome the host immune system
Replicate
Produce cell injury

Pathogenesis of Viral Infections

1. Entry and primary replication
Viruses enter the host through:
Respiratory tract
GI tract
Skin
Sexual contact

Some viruses replicate and produce disease at

the site of entry

Pathogenesis of Viral Infections

2. Spread of virus in the body
Many viruses migrate from the site of entry via
the bloodstream, lymphatics or nervous
system to reach the organ or tissue for which
they have an affinity
Once reaching these tissues, they find
susceptible cells with specific receptors on the
surfaces

Pathogenesis of Viral Infections

3. Cell damage and disease
After entering the body, the virus may remain
latent without multiplication or cause
widespread tissue damage
If damage result in cell death = cytocidal
If damage causes cell lysis = cytolytic
Damage can also be cellular proliferation or
malignant transformation (e.g. oncogenic
viruses causing malignancies)

Pathogenesis of Viral Infections

Cellular damage or destruction can be due to:
i. Viral nucleic acids which often inhibit protein
and DNA synthesis of the host cell
ii. Large amounts of viral proteins accumulated
in the host cell which exert toxic effects and
distort its structure
iii. There may be a change in permeability of
plasma membrane that may lead to autolysis

Pathogenesis of Viral Infections

iv. Viral antigens may appear on the cell surface,
e.g. haemagglutinin spikes of influenza virus
appear on the host cell surface which make
red cells adhere to them (haemadsorption)
v. Changes in the cytoplasmic membrane by the
respiratory syncytial virus bring about fusion
of adjacent cell membranes resulting in the
formation of big clumps or syncytia

Pathogenesis of Viral Infections

vi. Some viruses, e.g. measles, mumps,
adenoviruses, cytomegaloviruses and
varicella cause damage to the chromosome
of the host cell

Viral Diseases
Common viral disease:
1.
2.
3.
4.
5.
6.

AIDS
Hepatitis B
Hepatitis C
Rubella
Influenza (seasonal)
Herpes simplex virus infection

HIV
It is an RNA virus and belongs to the:
Family: Retroviridae
Subfamily: Lentiviridae

Two types of HIV viruses:

HIV type 1 (HIV-1)
HIV type 2 (HIV-2)

HIV-1 is the predominant type worldwide

HIV Morphology

HIV Morphology

HIV Envelope
Mature HIV virion is spherical in shape and
detaches from the surface of infected cell by a
process called budding
The viral envelope is therefore derived from
the host cell membrane
It is a lipid bilayer and is studded by envelope
glycoproteins, gp120 and gp41
Lining the lipid envelope is a structural protein,
p17 also referred to as the matrix protein

HIV Morphology

HIV budding

HIV
A RNA retrovirus - produces the enzyme
reverse transcriptase inside the host cells
The enzyme transforms viral RNA to DNA
provirus
Provirus is incorporated into the host cell DNA
The host cell then produces new copies of the
virus pass out into tissue fluid, blood and
infect other host cells.
When infected host cells divide, copies of the
provirus are integrated into the DNA of daughter
cells, spreading the disease within the body

HIV
HIV has an affinity for cells that have a protein
receptor called CD4 in their membrane
These cells include T-lymphocytes,
monocytes, macrophages, some Blymphocytes and cells in the GI tract and
neuroglial cells in the brain
T-lymphocytes are the main cells involved
HIV reduces their number, causing
suppression of both antibody-mediated and
cell-mediated immunity consequent
development of widespread opportunistic
infections

Acquired Immune Deficiency syndrome

(AIDS)
Infection is spread by:
1. Unprotected sexual intercourse (vaginal and
anal)
2. Contaminated needles

During treatments of patients

When drug abusers share needles

3. An infected mother to her child

Across the placenta before birth

During childbirth
Possibly by breast milk

Acquired Immune Deficiency syndrome

(AIDS)
NOTE: The presence of antibodies to HIV
indicates that the individual has been exposed
to the virus BUT NOT that a naturally acquired
immunity has developed.
NOT ALL those who have antibodies in their
blood develop AIDS although they may act as
carrier and spread the infection to others

Acquired Immune Deficiency syndrome

(AIDS)
Symptoms
A few weeks after initial infection: acute
influenza-like illness with no specific features
Followed by a period of 2 or more years
without symptoms
Chronic HIV infection may cause persistent
generalised lymphadenopathy (PGL)
Some develop AIDS-related complex (ARC) and
chronic low-grade fever, diarrhoea, weight loss,
anaemia and leukopenia

Acquired Immune Deficiency syndrome

(AIDS)
When AIDS develop, the main complications
are widespread recurrent opportunistic
infections and tumours that includes:
Pneumonia, commonly caused by Pneumocystis
carinii
Persistent nausea, diarrhoea and weight loss
due to recurrent infections of GI tract
Meningitis, encephalitis and brain abscesses
may be recurrent due to opportunistic
microbes of HIV itself

Acquired Immune Deficiency syndrome

(AIDS)
Neurological function may deteriorate
(forgetfulness, loss of concentration, confusion,
apathy, dementia, limb weakness)
Skin eruptions, often widespread (e.g. eczema,
psoriasis, cellulitis, impetigo, warts, shingles
and cold sores)
Generalised lymphadenopathy (non-infective
enlargement of lymph nodes)

Acquired Immune Deficiency syndrome

(AIDS)
Development of malignant tumours because
progressive failure of immunological surveillance
as the virus destroys T cells population. Typical
cancers include:
Lymphomas (tumours of lymph nodes)
Kaposis sarcoma (tumours under the skin and in
internal organs)

Laboratory Diagnosis for HIV

It can take some time for the immune system
to produce enough antibodies for the
antibody test to detect - window period,
between infection with HIV and the ability to
detect it with antibody tests can vary from
person to person
A positive HIV test result means that a person
may have been infected with HIV

Laboratory Diagnosis for HIV

All positive HIV test results, regardless of
whether they are from rapid or conventional
tests, must be verified by a second
confirmatory HIV test

Hepatitis
Causes inflammation of liver
Primarily attacks hepatocytes
Viral hepatitis can be caused by:
Hepatitis Virus A (HAV)
Hepatitis Virus B (HBV)
Hepatitis Virus C (HCV)
Hepatitis Virus D (HDV)
Hepatitis Virus E (HEV)
Hepatitis Virus F (HFV)
Hepatitis Virus G (HGV)

Hepatitis A Virus Morphology

Among the smallest and structurally simplest
of the RNA viruses
Virion is non-enveloped, diameter of 27 - 32 nm
Composed entirely of viral protein and RNA.
Electron microscopy (EM) analyses show
particles with icosahedral symmetry although
no structural details could be discerned
Morphologically, HAV particles are
indistinguishable from other picornaviruses

Hepatitis A Virus Morphology

Hepatitis B Virus Morphology

Family - Hepadnaviridae
Icosahedral, spherical, enveloped, complex,
Larger than HAV,
42nm diameter, genome is double-stranded
DNA

Hepatitis B Virus Morphology

Hepatitis B Virus Antigenic Structure

Envelope contains - HB surface antigen (HBsAg)
Core contains HB core antigen (HBcAg) (antibodies produce against HBcAg during
primary infection)
HBe antigen - not a viral particle, translated
from RNA (reliable marker for infectivity)

Hepatitis B Diagnosis
By clinical data
Liver function test
Alanine amino transferase - gradual rise with
longer duration indicates HBV infection
Bilirubin and serum globulin increases; serum
albumin decreases.

Serology
Surface antigen - ELISA, latex agglutination test
Antigens - immunoflourescent test

Hepatitis B Diagnosis
Sero markers
Recent infection- HBsAg and IgM antibodies to
HBcAg
Chronic infection - anti HBcAg
Past infection - IgG antibodies

Molecular techniques
detection and quantitation of viral DNA by PCR

Hepatitis C Virus Morphology

Single strand of RNA, enveloped
Capable of rapid genetic variation to evade
hosts immune system
Hepatitis C aka silent epidemic - kills more
people than AIDS in the United States
Few people have recognisable symptoms until
about after 20 years infection undiagnosed

Hepatitis C Virus Morphology

Rubella
Rubella or German measles (first described by
German physicians in the 18th century)
Much milder disease than measles (rubeola)
Often undetected
Symptoms: macular rash of small red spots
and a light fever
Transmission is by the respiratory route
Incubation about 2 to 3 weeks

Rubella Morphology

Rubella
Once recover, will give immunity
Complications are rare, except in pregnant
women (especially in the 1st trimester)
severe birth defects or foetal death
Important to immunise all women of childbearing age

Rubella

Herpes Simplex Virus Infection

Herpes simplex virus can be separated:
HSV-1
HSV-2

HSV-1 is transmitted primarily by oral or

respiratory routes, infection usually occurs in
infancy
This infection is subclinical, but may develop
lesions known as cold sores or fever blisters
(painful, short-lived vesicles that occur near the
outer red margins of the lips)

Herpes Simplex Virus Morphology

HSV-1 Lesions

Herpes Simplex Virus Infection

HSV-1 remain latent in the trigeminal nerve
ganglia communicating between face and
central nervous system
Recurrences can be triggered by excessive
exposure to ultraviolet radiation from the sun,
emotional upsets, or the hormonal changes
associated with menstruation
HSV-1 can be transmitted by skin contact

Trigeminal Nerve Ganglia

Herpes Simplex Virus Infection

HSV-2 is very similar to HSV-1, but it is
transmitted primarily by sexual contact
The usual cause of genital herpes
HSV-2 is differentiated from HSV-1 by its
antigenic makeup and by its effects on cells in
tissue culture
It remains latent in the sacral nerve ganglia
found near the base of the spine

HSV-2 Genital Lesions

Influenza Virus
Influenza (flu) is characterised by chills, fever,
headache, and general muscular aches
Recovery normally occurs in a few days
Influenza viruses consist of 8 separate RNA
segments of differing lengths enclosed by a
inner layer of protein and an outer lipid
bilayer
Embedded in the lipid bilayer are numerous
projections that characterise the virus

Influenza Virus Morphology

Influenza Virus
These 2 types of projections:
Haemagglutinin (H) spikes (500 per virus)
Neuraminidase (N) spikes (100 per virus)

The H spikes allow the virus to recognise and

attach to the body cells before infecting them
Antibodies against the influenza virus are
directed mainly at these spikes
Haemagglutinin refers to the agglutination of
red blood cells that occurs when the viruses
are mixed with them

Influenza Virus
The N spikes enzymatically help the virus
separate from the infected cell as the virus exits
after intracellular reproduction
N spikes also stimulate the formation of
antibodies, but are less important than those
produced in response to H spikes
Viral strains are identified by variation in the H
and N antigens
The different forms of the antigens are assigned
numbers - e.g. H1, H2, H3, N1, and N2

Influenza Virus
There are 15 subtypes of H and 9 of N
Each number change represents a substantial
alteration in the protein makeup of the spike
These changes are called antigenic shifts, and
they are great enough to evade most of the
immunity developed in the human population
This ability is responsible for the outbreaks such
as the Spanish Flu in 1918, H2N2 outbreak in
Asia in 1957 and H3N2 outbreak in Hong Kong
in 1968

Influenza Virus
Antigenic shifts are probably caused by major
genetic recombination
Influenza viral RNA occurs as 8 segments,
recombination is likely in infections caused by
more than one strain
Recombination between the RNA of animal
viral strains (swine, horse, birds) and the RNA
of human strains might be involved

THE END