Viral Infections

July 2016
 Introduction
• Viruses are the cause of many clinically important
acute and chronic infections, which may affect
virtually every organ system.
• Are classified as different category based on the
immune response
1. Acute transient infections
2. Latent infections
3. Chronic productive infections
4. Onchogenic /Transforming viral infections
 Introduction continued

- Viruses are obligate intracellular organisms that

commandeer the host cell's biosythetic and
replicative apparatus for their own proliferation.

- They consist of a nucleic acid genome surrounded

by a protein coat (called a capsid) and,
occasionally, a host-derived lipid membrane.
• Viruses may be classified by some
combination of their nucleic acid genome
(DNA or ribonucleic acid [RNA], but not both),
the shape of the capsid (icosahedral or
helical), the presence or absence of a lipid
envelope, the mode of replication, the
preferred host cell type (called tropism), or
the type of pathology they cause.
- Because viruses are individually smaller than
the limits of light microscopic resolution (20-
300 nm in size), they are best visualized by
electron microscopy.
• However, certain viruses have the propensity
to aggregate within the cells they infect and
form characteristic inclusion bodies; these
may be visualized by light microscopy and may
be diagnostically helpful.
• Thus, CMV-infected cells are markedly
enlarged (hence the prefix cytomegalo-) and
have characteristic inclusion bodies-both
eosinophilic nuclear inclusions and smaller
basophilic cytoplasmic inclusions &
• Rabies virus form characteristic cytoplasmic
inclusions called negri body
 Measles (rubeola)
• Measles is an acute viral infection that affects
multiple organs and causes a wide range of
disease, from mild, self-limited infections to
severe systemic manifestations.

• Measles (rubeola) virus is a leading cause of

vaccine preventable death and illness
worldwide.
 continued
• Measles virus is a single-stranded RNA virus of
the paramyxovirus family, which includes
mumps, respiratory syncytial virus,
parainfluenza virus.

• There is only one serotype of measles virus.

 Measles continued
• Measles virus is transmitted by respiratory
droplets.

• Measles can replicate in a variety of cell types,

including epithelial cells and leukocytes.
 Measles continued
• The virus initially multiplies within the
respiratory tract and then spreads to local
lymphoid tissues. Replication of the virus in
lymphatic tissue is followed by viremia and
systemic dissemination to many tissues,
including the conjunctiva, skin, respiratory
tract, urinary tract, small blood vessels,
lymphatic system, and CNS.
• Most children develop T-cell–mediated
immunity to measles virus that helps control
the viral infection.

• Antibody-mediated immunity to measles virus

protects against re infection.
 Clinical Feature
• pneumonia,
• diarrhea and protein-losing enteropathy
• Keratitis leading to scarring and blindness,
encephalitis
• Hemorrhagic rash
 Morphology
• Dilated skin vessels, edema, and mononuclear
perivascular infiltrate.
• Ulcerated mucosal lesions in the oral cavity
near the opening of the Stensen ducts (the
pathognomonic Koplik spots) are marked by
necrosis, neutrophilic exudate, and
neovascularization.
 Morphology continued
• The lymphoid organs typically have marked
follicular hyperplasia, large germinal centers,
and randomly distributed multinucleate giant
cells, called Warthin-Finkeldey cells, which
have eosinophilic nuclear and cytoplasmic
inclusion bodies.
 Mumps
• Mumps is an acute systemic viral infection
usually associated with pain and swelling of
the salivary glands.

• Mumps virus is a member of the

paramyxovirus family.
 Mumps
• Mumps viruses enter the upper respiratory
tract through inhalation of respiratory
droplets, spread to draining lymph nodes
where they replicate in lymphocytes
(preferentially in activated T cells), and then
spread through the blood to the salivary and
other glands.
 Morphology
• Mumps parotitis is bilateral in 70% of cases. The
affected glands are enlarged, have a doughy
consistency, and are moist, glistening, and reddish-
brown on cross-section.
• On microscopic examination the gland
interstitium is edematous and diffusely
infiltrated by macrophages, lymphocytes, and
plasma cells, which compress acini and ducts.
Neutrophils and necrotic debris may fill the
duct lumen and cause focal damage to the
lining epithelium.
 Morphology
Mumps orchitis testicular swelling may be
marked, caused by edema, mononuclear cell
infiltration, and focal hemorrhages.
• Because the testis is tightly contained within
the tunica albuginea, parenchymal swelling
may compromise the blood supply and cause
areas of infarction. The testicular damage can
lead to scarring, atrophy, and, if severe,
sterility
• Infection and damage of acinar cells in the
pancreas may release digestive enyzmes,
causing parenchymal and fat necrosis and
neutrophil-rich inflammation.
• Mumps encephalitis causes perivenous
demyelination and perivascular mononuclear
cuffing.
 Latent Infections (Herpesvirus
Infections)
• Latency is defined as the persistence of viral
genomes in cells that do not produce
infectious virus.

• The viruses that most frequently establish

latent infections in humans are herpesviruses.
• These are large encapsulated viruses with
double-stranded DNA genomes that encode
approximately 70 proteins.

• The viruses persist in a noninfectious form

with periodic reactivation and shedding of
infectious viruses.
• There are three subgroups and eight types of
the virus.
• α-group viruses, including HSV-1, HSV-2, and
VZV which infect epithelial cells and produce
latent infection in neurons.
• β-group viruses, including CMV, human
herpesvirus-6 and human herpes virus -7
which infect and produce latent infection in a
variety of cell types.
• the γ-group viruses EBV and KSHV/HHV-8, the
cause of Kaposi sarcoma, which produce
latent infection mainly in lymphoid cells.
 Herpes Simplex Viruses
• HSV-1 and HSV-2 differ serologically but are
closely related genetically and cause a similar
set of primary and recurrent infections.
• Both viruses replicate in the skin and the
mucous membranes at the site of entry of the
virus (usually oropharynx or genitals), where
they produce infectious virions and cause
vesicular lesions of the epidermis.

• The viruses spread to sensory neurons that

innervate these primary sites of replication.
• Reactivation of HSV-1 and HSV-2 may occur
repeatedly with or without symptoms, and
results in the spread of virus from the neurons
to the skin or to mucous membranes.

• Reactivation can occur in the presence of host

immunity.
 Morphology
• HSV-infected cells contain large, pink to purple
intranuclear inclusions (Cowdry type A) that
consist of viral replication proteins and virions
at various stage of assembly that push the
host cell chromatin out to the edges of the
nucleus.
Cowdary type a inclusion
Herpes labialis
• HSV-1 and HSV-2 cause lesions ranging from
self-limited cold sores and gingivostomatitis to
life-threatening disseminated visceral
infections and encephalitis.
• Gingivostomatitis, which is usually
encountered in children,is caused by HSV-1. It
is a vesicular eruption extending from the
tongue to the retropharynx and causing
cervical lymphadenopathy. Swollen,
erythematous HSV lesions of the fingers or
palm (herpetic whitlow) occur in infants and,
occasionally, in health care workers.
Inclusion bodies in herpes blister
• Genital herpes is more often caused by HSV-2
than by HSV-1. It is characterized by vesicles
on the genital mucous membranes as well as
on the external genitalia that are rapidly
converted into superficial ulcerations, rimmed
by an inflammatory infiltrate
• Herpesvirus (usually HSV-2) can be
transmitted to neonates during passage
through the birth canal of infected mothers.
Although HSV-2 infection in the neonate may
be mild, more commonly it is fulminating with
generalized lymphadenopathy, splenomegaly,
and necrotic foci throughout the lungs, liver,
adrenals, and CNS.
 Varicella zoster virus
• Acute infection with VZV causes chickenpox
and reactivation of latent VZV causes shingles
(also called herpes zoster).
• VZV is transmitted in epidemic fashion by
respiratory aerosols, disseminates
hematogenously, and causes widespread
vesicular skin lesions.
• Chickenpox is mild in children but more severe
in adults and in immunocompromised people.

• VZV infects mucous membranes, skin, and

neurons and causes a self-limited primary
infection in immuno competent individuals.
• Latent VZV infection is seen in neurons and/or
satellite cells around neurons in the dorsal
root ganglia.
• Localized recurrence of VZV is most frequent
and painful in dermatomes innervated by the
trigeminal ganglia,
 Morphology
• The chickenpox rash occurs approximately 2
weeks after respiratory infection.
• Lesions appear in multiple waves centrifugally
from the torso to the head and extremities.
• Each lesion progresses rapidly from a macule to a
vesicle, which resembles a dewdrop on a rose
petal.
• On histologic examination, chickenpox lesions
show intraepithelial vesicles with intranuclear
inclusions in epithelial cells at the base of the
vesicles
Vesicle in chickenpox
 Morphology continued
• Shingles occurs when VZV that has long
remained latent in the dorsal root ganglia
after a previous chickenpox infection is
reactivated.
 Cytomegalovirus (CMV),
• Cytomegalovirus (CMV), a β-
groupherpesvirus, can produce a variety of
disease manifestations, depending on the age
of the host, and, more importantly, on the
host’s immune status.
• CMV latently infects monocytes and their
bone marrow progenitors and can be
reactivated when cellular immunity is
depressed.
• Transmission of CMV can occur by several
mechanisms
1.Transplacental
2. Neonatal
3.Through saliva
4.Throug genital tract
5. Iatrogenic
 Congenital Infections
• 95% are asymptomatic

• Classic cytomegalic inclusion disease develops

if the mother acquires primary infection before
the formation of antibodies.
 Congenital
• Classic cytomegalic inclusion disease
• IUFD
• Hepatomegally
• Jaundice
• Microcephaly
• Anemia
• Bleeding
• Diagnosis of neonatal CMV is made by viral
culture or PCR amplification of viral DNA in
urine or saliva.
 Perinatal Infections
• . Infection acquired during passage through
the birth canal or from breast milk is usually
asymptomatic due to protective maternal
anti-CMV antibodies, which are transmitted to
the fetus across the placenta.
 Cytomegalovirus Mononucleosis
• fever,
• atypical lymphocytosis, lymphadenopathy,
and hepatitis, marked by hepatomegaly and
abnormal liver function tests.

• The diagnosis is made by serology. Most

people recover without seqaule
• infected individuals remain seropositive for
life and the virus is never cleared, persisting in
latently infected leukocytes.
 CMV in Immunosuppressed
Individuals.
• Immunocompromised individuals (e.g.,
transplant recipients, HIVinfected individuals)
are susceptible to severe CMV infection; these
may be either primary infections or
reactivation of latent CMV.
• CMV pneumonitis
• CMV colitis
 Diagnosis
• Diagnosis of CMV infections is made by
demonstration of characteristic morphologic
alterations in tissue sections
• Viral culture
• Rising antiviral antibody titer
• Detection of CMV antigens
• PCR-based detection of CMV DNA.
 Transforming Viral Infections
• Some viruses can transform infected cells into
benign or malignant tumor cells.
e.g.
EBV ,HTLV-1 and HBV
 Epstein-Barr Virus (EBV)
• EBV causes infectious mononucleosis, a
benign, selfl imited lymphoproliferative
disorder

• Associated with the pathogenesis of several

human tumors, most commonly certain
lymphomas and nasopharyngeal carcinoma.
• Infectious mononucleosis occurs principally in
late adolescents or young adults among upper
socioeconomic classes in developed nations.
 Clinical manifestation of Infectious
Mono
Fever
• Sore throat
• Generalized lymphadenopathy
• Splenomegaly,
• Atypical activated T lymphocytes
(mononucleosis cells).
• Some people develop hepatitis,
meningoencephalitis, and pneumonitis.
 EBV
• EBV infects B cells and possibly epithelial cells
of the oropharynx.
• EBV is shed in the saliva. It is not known
whether the source of the virus is B cells,
oropharyngeal epithelial cells, or both.
• Cellular immunity mediated by CD8+ cytotoxic
T cells and NK cells.
 Morphology
• The peripheral blood shows absolute
lymphocytosis; more than 60% of white blood
cells are lymphocytes.

• Generalized lymphadenopathy with expansion

of the para cortex.
• Hepatospleenomegaly