Cytomegalovirus (CMV) : R.Varidianto Yudo T., Dr.,Mkes

R.Varidianto Yudo T., dr.,MKes.
Lab. Mikrobiologi
Fakultas Kedokteran Universitas Hang Tuah
CYTOMEGALOVIRUS (CMV)
Diseases
CMV causes cytomegalic inclusion disease

(especially congenital abnormalities) in
neonates.
It is the most common cause of congenital
abnormalities in the United States.
It also causes pneumonia and other diseases
in immunocompromised patients and
heterophil-negative mononucleosis in
immunocompetent individuals.
Important Properties
CMV is structurally and morphologically

identical to other herpesviruses but is
antigenically different.
It has a single serotype.
Humans are the natural hosts; animal CMV
strains do not infect humans.
Giant cells are formed, hence the name
"cytomegalo."
Replicative Cycle
The cycle is similar to that of HSV

One unique feature of CMV replication is that
some of its "immediate early proteins" are
translated from mRNAs brought into the
infected cell by the parental virion rather than
being translated from mRNAs synthesized in
the newly infected cell.
Transmission & Epidemiology
CMV is transmitted by a variety of modes.

Early in life it is transmitted across the
placenta, within the birth canal, and quite
commonly in breast milk.
In young children, its most common mode of
transmission is via saliva.
Later in life it is transmitted sexually; it is
present in both semen and cervical
secretions.
It can also be transmitted during blood
transfusions and organ transplants.
CMV infection occurs worldwide, and more
than 80% of adults have antibody against this
virus.
Pathogenesis & Immunity
Infection of the fetus can cause cytomegalic

inclusion disease, characterized by
multinucleated giant cells with prominent
intranuclear inclusions.
Many organs are affected, and widespread
congenital abnormalities result.
Infection of the fetus occurs mainly when a
primary infection occurs in the pregnant woman,
i.e., when she has no antibodies that will
neutralize the virus before it can infect the fetus.
The fetus usually will not be infected if the
pregnant woman has antibodies against the
virus.
Congenital abnormalities are more common
when a fetus is infected during the first trimester
than later in gestation, because the first
trimester is when development of organs occurs
and the death of any precursor cells can result in
congenital defects.
Infections of children and adults are usually
asymptomatic, except in immunocompromised
individuals.
CMV enters a latent state in leukocytes and can
be reactivated when cell-mediated immunity is
decreased.
CMV can also persist in kidneys for years.
Reactivation of CMV from the latent state in
cervical cells can result in infection of the
newborn during passage through the birth canal
CMV has a specific mechanism of "immune
evasion" that allows it to maintain the latent
state for long periods.
In CMV-infected cells, assembly of the MHC class
Iviral peptide complex is unstable, so viral
antigens are not displayed on the cell surface
and killing by cytotoxic T cells does not occur.
CMV infection causes an immunosuppressive
effect by inhibiting T cells.
Host defenses against CMV infection include
both circulating antibody and cell-mediated
immunity.
Cellular immunity is more important, because its
suppression can lead to systemic disease.
Clinical Findings
Approximately 20% of infants infected with CMV

during gestation show clinically apparent
manifestations of cytomegalic inclusion disease
such as microcephaly, seizures, deafness,
jaundice, and purpura.
Hepatosplenomegaly is very common.
Cytomegalic inclusion disease is one of the
leading causes of mental retardation in the
United States.
Infected infants can continue to excrete CMV,
especially in the urine, for several years.
In immunocompetent adults, CMV can cause
heterophil-negative mononucleosis, which is
characterized by fever, lethargy, and the
presence of abnormal lymphocytes in peripheral
blood smears.
Systemic CMV infections, especially
pneumonitis and hepatitis, occur in a high
proportion of immunosuppressed patients, e.g.,
those with renal and bone marrow transplants.
In AIDS patients, CMV commonly infects the
intestinal tract and causes intractable colitis.
CMV also causes retinitis in AIDS patients, which
can lead to blindness.
Microcephaly with associated severe psychomotor
retardation and hepatosplenomegaly in congenital
cytomegalovirus infection
Laboratory Diagnosis
The preferred approach involves culturing in

special tubes called shell vials coupled with the
use of immunofluorescent antibody, which can
make a diagnosis in 72 hours.
If available, polymerase chain reaction (PCR)-
based assays that detect viral nucleic acids are
also useful.
Other diagnostic methods include fluorescent-
antibody and histologic staining of inclusion
bodies in giant cells in urine and in tissue.
The inclusion bodies are intranuclear and have an
oval owl's-eye shape.
A fourfold or greater rise in antibody titer is also
diagnostic.
PCR-based assays for CMV DNA or RNA in tissue or
body fluids, such as spinal fluid, and amniotic fluid
are also very useful.
CMV antigenemia can be measured by detecting
pp65 within blood leukocytes using an
immunofluorescence assay.
pp65 is a protein located in the nucleocapsid of CMV
and can be identified within infected leukocytes
using fluorescein-labeled monoclonal antibody
specific for pp65.
CytomegalovirusOwl's-eye inclusion body
Treatment
Ganciclovir (Cytovene) is moderately

effective in the treatment of CMV retinitis
and pneumonia in patients with AIDS.
Valganciclovir, which can be taken orally, is
also effective against CMV retinitis.
Foscarnet (Foscavir) is also effective but
causes more side effects.
Unlike HSV and VZV, CMV is largely resistant
to acyclovir.
Prevention
There is no vaccine.
Ganciclovir can suppress progressive retinitis in AIDS
patients.
Infants with cytomegalic inclusion disease who are
shedding virus in their urine should be kept isolated from
other infants.
Blood for transfusion to newborns should be CMV
antibody-negative.
If possible, only organs from CMV antibody-negative
donors should be transplanted to antibody-negative
recipients.
A high-titer immune globulin preparation (CytoGam) is
used to prevent disseminated CMV infections in organ
transplant patients

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R.Varidianto Yudo T., dr.,MKes.

CMV causes cytomegalic inclusion disease

CMV is structurally and morphologically

The cycle is similar to that of HSV

CMV is transmitted by a variety of modes.

Infection of the fetus can cause cytomegalic

Approximately 20% of infants infected with CMV

The preferred approach involves culturing in

Ganciclovir (Cytovene) is moderately

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