Everything About The Cytomegalovirus
Date: 3 سال قبل
author: AmirAbad
Cytomegalovirus
Cytomegalovirus (CMV) is a genus of herpesvirus in the
subfamily of β-Herpesvirinae.
CMV is the prototypical β-herpesvirus.
VIRION STRUCTURE
The HCMV virion ranges from
200 to 300 nM in diameter. The virion tegument layer resides
between the envelope and the capsid and remains the least well-characterized
region of the virion both in terms of composition and organization. The
tegumented nucleocapsid is surrounded by a lipid bilayer envelope derived from
the endoplasmic reticulum–Golgi intermediate compartment and contains a large
number of virusencoded proteins. The envelope exhibits a unique lipid content
including very long chain fatty acids and cholesterol that distinguishes it
from membranes of uninfected cells.
Genome Organization
The HCMV genome is one of
the largest and most complex of any characterized herpesvirus.Initial DNA
sequence analysis, together with follow-up investigatn established the presence
of 40 conserved core protein-coding genes common to all subfamilies of
mammalian herpesviruses along with a larger subset (~70) conserved across the β-herpesviruses
with some of these encoding late transcription
Clinical Manifestations
Cytomegalovirus causes
three clinical syndromes.Congenital cytomegalovirus infection (when
symptomatic) causes hepatosplenomegaly, retinitis, rash, and central nervous
system involvement. In about 10 per cent of older children and adults, primary
cytomegalovirus infection causes a mononucleosis syndrome with fever, malaise,
atypical lymphocytosis, and pharyngitis. Immunocompromised hosts (transplant
recipients and human immunodeficiency virus [HIV]-infected individuals) may
develop life-threatening disseminated disease involving the lungs,
gastrointestinal tract, liver, retina, and central nervous system.
PATHOGENESIS AND PATHOLOGY
HCMV infection and
transmission in most people proceeds without symptoms or disease.Clinically
apparent manifestations of HCMV infection are expressed almost exclusively in
the context of congenital infection and in the immunocompromised host,
including transplant recipients and HIV/AIDS and cancer patients undergoing
immunosuppressive chemotherapy.This virus is also an occasional cause of
infectious mononucleosis. Characteristics of CMVdisease are discussed in
section Clinical Features. Numerous books, reviews, and chapters have described
person-to-person transmission, dissemination, and host control characteristics
that place individuals at risk for HCMV disease. From initial infection at the
mucosal epithelium, HCMV infects diverse cell types and tissues, causing a
systemic infection with persistent and sporadic shedding for life.
as discussed in section
Latency. Entry and Transmission Community acquisition of HCMV follows mucosal
exposure to virus that is shed into oral and genital fluids, urine, and breast
milk. Thus, repeated exposures to infectious virus in saliva or urine leads to
virus transmission in adults and young children. Individuals exposed to infants
shedding virus and infants exposed to HCMV through breast-feeding are high-risk
settings for infection. Approximately 50% of breast-fed infants born to HCMV
seropositive women will acquire the virus in the first few months of life and
subsequently shed virus in saliva and urine for prolonged periods of time
during infancy, exposing others. The high incidence of transmission in these
settings makes these important routes of community acquired infections
worldwide Rates of
transmission between children less than 2 years of age are also elevated,
likely the result of frequent exchange of saliva between young children.
In adults, sexual
transmission has been documented with virus shed into both cervical secretions
and semen.
Transfusion of blood
products from HCMV infected donors has long been known to represent a
significant risk for the acquisition of HCMV and as a result, blood products
from noninfected donors or that are leukocyte depleted are now commonly
employed for transfusion of at risk individuals such as premature infants and
pediatric transplant recipients.
Diagnosis
The detection of HCMV DNA
by quantitative PCR is the most frequently employed approach for the diagnosis
of HCMV infection, and serial measurements of viral DNA has largely replaced
other assays for virologicalmonitoring patients at risk for invasive HCMV infection.
PREVENTION AND CONTROL
Antiviral agents have been
used to control HCMV infections in allograft recipients, individuals with
HIV/AIDS, and, more recently, infants with cCMV infections.
A recently approved
antiviral agent, letermovir, has been shown to be of considerable value in HCMV
prophylaxis in HCT recipients secondary to both its antiviral activity and,
importantly,a lack of myelosuppression that is associated with ganciclovir
therapy. Letermovir is a small molecule inhibitor that specifically inhibits
the packaging of HCMV DNA but not rodent CMVs or other herpesviruses
Epidemiology
Transmission is via
intimate contact with infected secretions. Cytomegalovirus infections are among
the most prevalent viral infections worldwide.
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