CHAPTER 13
VIRAL PATHOGENESIS
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Microbiology: A Clinical Approach © Garland Science
WHY IS THIS IMPORTANT?
• Most infections are caused by viruses.
• Health care professionals must understand the
pathogenic mechanisms used by these
pathogens.
PATTERNS OF VIRAL
INFECTION
• Viral infections can be:
• Acute (rapid and self limiting)
• Persistent (long term)
• Latent (extreme versions of persistent
infections)
• Slow or transforming (complicated types of
persistent infections)
PATTERNS OF VIRAL
INFECTION
• Cytopathic viruses produce virions and kill
host cells rapidly (cytopathology).
• Noncytopathic viruses produce virions but do
not cause cytopathology.
• Some viruses do not produce virions or cause
cytopathology but still cause infection.
PATTERNS OF VIRAL
INFECTION
• Incubation periods vary for different viruses.
• Some are as short as days.
• Some are as long as years.
• During the incubation period:
• The virus is replicating.
• The host is beginning to respond
PATTERNS OF VIRAL
INFECTION
ACUTE INFECTIONS
Microbiology: A Clinical Approach © Garland Science
ACUTE INFECTIONS
• Acute viral infections are severe public health
problems.
• They are usually associated with epidemics.
• The main problem is the short incubation
period.
• This causes a delay in identifiable symptoms
until the virus has already spread.
• Acute infection epidemics are often seen in
crowded populations.
• Schools
• Military bases and Nursing homes
DISSEMINATION AND TRANSMISSION OF
VIRAL INFECTION
• Viral infections are disseminated within the
host and transmitted from one host to another.
• There are three basic requirements for
successful infection:
• Sufficient number of viruses present
• The number depends on the type of virus,
the site of infection, and the age and health
of the host.
• Access to susceptible and permissive host
cells
• An ineffective host immune response
VIRAL DISSEMINATION
The three main entry points are:
• Respiratory system
• Digestive tract
• Urogenital tract
• The most common portal of entry into the human
body.
• It is always exposed to large numbers of
potential pathogens.
• Viruses easily disseminate from here into other
areas of the body.
VIRAL DISSEMINATION:
Urogenital Tract
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Microbiology: A Clinical Approach © Garland Science
VIRAL DISSEMINATION:
Other Portals of Entry
© CDC/ Dr. K. L. Hermann
Microbiology: A Clinical Approach © Garland Science
VIRAL DISSEMINATION:
Skin
Some viruses enter through the skin.
• Usually by vector transmission from biting
insects
• If they remain in the epidermis, a localized,
acute infection occurs.
• If they get into the dermis, a systemic
infection can occur.
VIRAL DISSEMINATION:
Nervous System
Some viruses can enter the body through the
nervous system.
• They can disseminate throughout the entire
body.
• Some target neurons.
• Some use neurons to get to their preferred
target area.
VIRAL DISSEMINATION:
Organs
•Viruses released from the apical surface host cells
cause localized limited infection.
•Viruses released from the basement membrane of
host cells can spread systemically.
•The bloodstream is the best route for systemic viral
infection.
•Referred to as hematogenous dissemination
•Viremia refers to virus replicating in the blood
VIRAL TRANSMISSION
Viral transmission refers to the spread of the virus
from one host to another.
•There are two patterns of viral transmission:
•Transmission within a single species
•Human to human.
•Transmission between species
• Animal to human
VIRAL TRANSMISSION
Viruses can be transmitted in several ways:
•Via inanimate objects
•Via poor techniques employed by health care
workers:
•This type of transmission is referred to as
iatrogenic transmission.
•Fecal-oral route – the digestive tract
VIRAL TRANSMISSION
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Microbiology: A Clinical Approach © Garland Science
VIRULENCE
There are three ways to measure viral virulence:
•LD50 – how much virus is required to kill 50%
of a subject population
•ID50 – how much virus is required to infect
50% of a subject population
•PD50 – how much virus is required to paralyze
50% of a subject population.
VACCINE DEVELOPMENT
•There are three groups of vaccines:
•Live attenuated vaccine –made of intact
virions rendered non-infectious
•Inactivated or killed vaccine – composed of
killed or dead virions
•Subunit vaccine – composed of immunogenic
parts of virions.
VACCINE DEVELOPMENT
Vaccination causing immunization can be either
active or passive.
•Active immunization – antigen is administered
and causes the onset of the immune response
•Passive immunization – a preformed antiviral
product, such as antibody, is administered.
VIRUSES AND CANCER
Some viruses can cause cancer in animals.
•An estimated 20% of human cancers involve
viruses.
•Retroviruses can inactivate genes responsible
for suppressing tumor formation.
Viruses associated with human cancers include:
Epstein-Barr virus
Hepatitis B and C viruses
HPV
Viruses and Cancer
 Mechanism of
cancer causation
23
A. Influenza
Properties:
 Member of the Orthomyxovirus family
 Enveloped RNA virus
 Packaged into helical nucleocapsids
 Antigenic variation & genetic exchange lead
to the appearance of new strains; requires
use of different vaccine combinations each
year
…. Influenza
Symptoms & Complications of Influenza:
 Respiratory Tract Symptoms
 Fever
 Neurological Complications:
Guillain-Barré Syndrome
 Reye’s Syndrome

B.Diseases Caused by the
Herpes Family
Properties of the Herpes Virus Family:
 Large, enveloped DNA viruses
 Icosahedral capsids ( regular polyhedron
with 20 identical equilateral triangular faces,
30 edges and 12 vertices.
 DNA replicates in the nucleus of host cells
 Cells may become permanently infected
 Host chromosomes may be altered
 Herpes infections associated with certain
cancers
… Diseases Caused by the
Herpes Family
Herpes Simplex:
 Two major strains
 Type I: Oral Herpes
 Type II: Genital Herpes
 Skin lesions form at site of the infection
 Virus travels along sensory neurons to ganglia,
where it remains
 During times of stress or weakened immunity,
virus may travel along same neurons to reinfect the initial skin sites
Oral herpes- infects the face and mouth.
The visible symptoms of which are colloquially called cold
sores or fever blisters, infects the face and mouth.
Genital herpis
Genital herpes- known simply as herpes
…. Herpes Simplex (cont.)
Other complications with Herpis simplex:
 Herpes encephalitis- inflammation or infection of the
brain and central nervous system (CNS).



Congenital herpes-birth-acquired herpes is a
herpes virus infection that an infant gets
(acquires) at the time of birth
Cervical cancer –cancer of the cervix
Bell's palsy is a dysfunction of cranial nerve
VII that results in inability to control facial
muscles on the affected side (Check images
of Bell palsy)
 Treatment: Acyclovir ( Antiviral medicine)
….. Diseases Caused by the
Herpes Family
Chicken pox & Shingles:
Cause: Varicella-zoster virus
 Chicken pox symptoms –rashes (Check images)
 A rash appears on the skin on the first day of
the disease.
 Tiny red spots on the skin, mostly on the upper
back or chest.
 In severe cases, a rash may appear on the face
and lower extremities.
 The papules turn into blisters and finally
become pustules and form scabs, which fall off
 Treatment -Chicken pox vaccine
Shingles:
 The chickenpox virus reactivates and causes shingles (
Check images)
 Early symptoms of shingles include headache,
sensitivity to light, and flu-like symptoms without a
fever
…. Diseases Caused by the
…Herpes Family
Infectious mononucleosis Disease
 Cause: Epstein-Barr virus (EBV)
 Infectious mononucleosis, or "mono“
 Also called as human herpes virus 4 (HHV-4),
is a possible, but not scientifically proven,
cancer causing virus of the herpes
 Lymph node swelling; fever; fatigue (check
images)
 The virus spreads through saliva, which is why
it's sometimes called "kissing disease.“
 Mono occurs most often in 15 to 17-year-olds
Monotest
 Mononucleosis tests are blood tests to look for
antibodies that indicate mononucleosis (mono)
caused by EBV
 The antibodies are made by the immune
….Diseases Caused by the
Herpes Family
Cytomegalovirus
 Congenital CMV ( present at birth) or
cytomegalovirus (Check images)
 CMV is the most common virus transmitted to
a pregnant woman's unborn child, person to
person, through close contact with body fluids
(urine, saliva (spit), breast milk, blood, tears,
semen, and vaginal fluids
 Mild symptoms in healthy individuals
.. Cytomegalovirus
CMV
 Approximately 1 in 150 children is born with
congenital CMV infection
 Miscarriages when contracted during
pregnancy
 Severe infections in AIDS patients
 Major cause of blindness in AIDS patients
 No vaccine currently…preventive
SummaryHERPES VIRUS TYPES THAT INFECT
HUMANS
 Herpes simplex virus Type 1 (HSV-1)
 Herpes simplex virus Type 2 (HSV-2)
 Epstein Barr virus (EBV) Cytomegalovirus
 (CMV) Varicella Zoster Virus (VZV)
 Human herpes virus 6
 Human herpes virus 8
Once a patient has become infected by herpes virus, the
infection remains for life
Viral Hepatitis
Hepatitis A:
 Also known as:
 Infectious hepatitis
 Short-incubation hepatitis
 Viral Properties:
 Picornavirus Family
 Small nonenveloped RNA viruses
 Family includes common cold (rhinovirus) &
polio viruses
Viral Hepatitis
 http://images.search.yahoo.com/search/images?_adv_
prop=image&fr=yfp-t-701&va=hepatitis+a&sz=all
.. Viral Hepatitis
Hepatitis A (cont.)
 Transmission:



Virus particles are present in the stool
Fecal-oral route via contaminated food or
water
Saliva contact, sexual contact, and
arthropods also have been implicated
.. Viral Hepatitis
Hepatitis A (cont.)
 Symptoms:
 Two to four week incubation period
 Nausea, vomiting, fever
 Abdominal pain
 Jaundice in many but not all cases
 Duration usually several weeks
… Viral Hepatitis
Hepatitis A (cont.)
 Treatment & Prevention:




Prolonged rest
Hepatitis A Immune Globulin- (IG)
contains antibodies that protect the body
from hepatitis A.
It's similar to the hepatitis A vaccine
Hepatitis A vaccine
… Viral Hepatitis
Hepatitis B:
 Also known as:
 Serum hepatitis
 Long-incubation hepatitis
…Viral Hepatitis
Hepatitis B (cont.)
 Viral properties:






Hepadnavirus family
Nucleocapsid consists of DNA surrounded by
hepatitis B core antigen (HBcAg)HBcAg (core antigen) is a hepatitis B viral protein
The core is surrounded by a lipoprotein envelope
containing the hepatitis B surface antigen (HBsAg)
The virus has also been called the Dane particle
Large amounts of excess HBsAg are found in the
serum & may be detected serologically
…Hepatitis B
 Hepatitis B infection occurs when liver cells become
infected with the hepatitis B virus (HBV).
 Viral hepatitis is the leading cause of liver cancer and
the most common reason for liver transplantation.
..Hepatitis B
.. Viral Hepatitis
Hepatitis B (cont.)
 Transmission:
 Contact with infected body fluids
 Blood, blood products, semen, vaginal secretions
(urine, saliva also implicated).
… Viral Hepatitis
Hepatitis B (cont.)
 Symptoms:







Incubation period: four weeks - six months
Nausea, fever
Dark urine & clay-colored stools
Abdominal tenderness
Jaundice
Duration of symptoms: 3 - 4 months
About 10% of patients remain carriers for several
months
…. Viral Hepatitis
Hepatitis B (cont.)
 Treatment & prevention

Hepatitis B Immune Globulin-Hepatitis B
Immune Globulin- (IG) contains antibodies
that protect the body from hepatitis B.

Hepatitis B vaccination
….Viral Hepatitis
Hepatitis C:
Hepatitis C infects the liver.
 It can lead to permanent liver damage, liver
cancer, and liver failure.
 Enveloped virus of the Flavivirus family
 Transmission & symptoms similar to B

..Viral Hepatitis
Hepatitis D (Delta hepatitis):
 A small defective RNA virus that requires
coinfection with Hepatitis B to replicate
 Co-transmitted with Hepatitis B
 Delta agent is a type of virus called hepatitis D
that causes symptoms only in people who have a
infection
…. Viral Hepatitis
Hepatitis E:
 small nonenveloped RNA virus of the calcivirus
family
 Transmission & symptoms similar to Hepatitis A
 Just like all the other types of viral hepatitis ,
hepatitis E causes liver swelling and damge
 Hepatitis E transmission like there is for Hepatitis A
Human Immunodeficiency
Virus (HIV)
 HIV (human immunodeficiency virus) is a virus that
attacks the immune system ( the body’s natural
defense system).
 Without a strong immune system, the body has trouble
fighting off disease.
 Both the virus and the infection it causes are called
HIV.
…Human Immunodeficiency
Virus (HIV)
Viral Properties
 A retrovirus
 An enveloped RNA virus that replicates through
a DNA intermediate
 The DNA intermediate is synthesized by reverse
transcriptase: an enzyme that makes a DNA
molecule using an RNA template
 The DNA intermediate is spliced into host
chromosomes, making the infection permanent
….Human Immunodeficiency
Virus
Transmission
 Contact with infected body fluids
 Blood, blood products, semen, vaginal
secretions, breast milk
 Symptoms of HIV patients:Check images
….Human Immunodeficiency
Virus
What is the difference between HIV & AIDS?
 HIV: the Human Immunodeficiency Virus
 The cause of AIDS
 Also known as: HTLV-III and LAV
 Two known types: HIV-1 and HIV-2
 AIDS: Acquired Immune Deficiency Syndrome
 Catastrophic immune system failure caused
by HIV infection
 Symptoms & cases are usually defined by the
CDC case surveillance definition
….. Human Immunodeficiency
Virus
Homework:
1.Check images of HIV & AIDS symptoms in patients
2. CDC Case Surveillance Definition for AIDS ?
 Category 1,2,3…
 Category A,B,C…
…. Human Immunodeficiency
Virus
Symptoms & Secondary Infections Associated with
AIDS:
 Acute Infection
 Fever, lymph node swelling, aches, fatigue,
“flu-like” or “mono-like” symptoms
 Persistent Generalized Lymphadenopathy
 Lymph node swelling for greater than 6
months in two or more body areas (excluding
the groin)
 Often an early manifestation that AIDS has
developed
….Human Immunodeficiency
Virus
Symptoms & Secondary Infections Associated with AIDS
(cont.):
 Constitutive Illness
 Weight loss, persistent fever, diarrhea
 Cancers
 Kaposi’s sarcoma (type of cancer)
 Certain lymphomas
Kaposi’s sarcoma
Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8
(HHV8), also known as Kaposi's sarcoma-associated herpesvirus
(KSHV)
…Human Immunodeficiency
Virus
Symptoms & Secondary Infections Associated with AIDS
(cont.):
 Bacterial Secondary Infections
 Mycobacterium
 Listeria
 Salmonella
 Mycoplasma
 Many others
….Human Immunodeficiency
Virus
Symptoms & Secondary Infections Associated with AIDS
(cont.)
 Fungal Secondary Infections
 Candida and others
 Protozoan Secondary Infections
 Toxoplasma gondii
 Cryptosporidium
 Pneumocystis carinii
…. Human Immunodeficiency
Virus
Symptoms & Secondary Infections Associated with AIDS
(cont.):
 Viral Secondary Infections
 Herpes simplex
 Cytomegalovirus
 Many others
 Treatments
 Inhibitors of DNA replication
 Protease Inhibitors
E. Miscellaneous Viral
Diseases
 Miscellaneous Pneumotrophic (viral diseases
involving respiratory tract) such as influenza and
common colds Viruses:
 Rhinovirus
 Adenovirus
 Respiratory Syncytial Virus-Respiratory
syncytial virus (RSV), which causes infection of
the lungs and breathing passages, is a major
cause of respiratory illness in young children
….Miscellaneous Viral
Diseases
Miscellaneous Dermotrophic Viruses
 Measles (Rubeola)
 Rubella
 Mumps
 Fifth disease
 Papilloma (HPV)
..
Miscellaneous Viral
Diseases
Miscellaneous Neurotrophic Viruses:
 Poliomyelitis
 Rabies
 Arbovirus
 Arenavirus (lymphocytic choriomeningitis)
 Others..several
Top ten Infectious diseases
 http://search.yahoo.com/search;_ylt=A0geu510a4tJ
JPoAS8VXNyoA?p=list+of+deadly+virus&y=Search
&fr=yfp-t-501-s
Bibliography
 Microbiology, A clinical Approach -Danielle
Moszyk-Strelkauskas-Garland Science 2010
 http://en.wikipedia.org/wiki/Scientific_metho
d
 https://files.kennesaw.edu/faculty/jhendrix/bio
2261/home.html
 http://www.cdc.gov/cmv/