General Information and Structure: Cytomegalovirus (CMV) is
a member of the betaherpesvirinae subfamily of herpesviruses. Replication in
betaherpesvirinae is much slower compared to the alphaherpesvirinae (e.g., herpes
simplex virus-1 and -2). CMV is ubiquitous human pathogen that has infected up
to 80% of adults by the age of 40. It remains an important opportunistic
pathogen in immunocompromised patients, especially those with HIV/AIDs. Similar
to other herpesviruses, CMV has a dsDNA genome contained within an icosahedral
nucleocapsid that is enveloped.
Pathobiology: CMV primarily infects monocytes, granulocytes,
lymphocytes, and epithelial cells. It rapidly establishes a latent infection in
monocytes, CD34+ hematopoietic progenitor cells, and endothelial cells. The
virus has evolved many strategies to evade immune detection and promote latent
infection including decreasing antigen presentation in MHC I and MHC II. In the
immunocompetent person, reactivation is rare due to cell-mediated immune system
mechanisms. When these mechanisms are suppressed (e.g., HIV/AIDs,
corticosteroids), reactivation can occur.
Epidemiology: CMV is distributed worldwide and does not
display seasonal fluctuations in incidence. Humans are the only reservoir and
transmit CMV horizontally through sexual contact, blood, tissue, and other
bodily fluids, or vertically through placental transmission, intrauterine, and
breast milk/colostrum. Therefore, fetuses, infants, blood and organ recipients,
and immunocompromised people are most at risk for becoming infected.
Laboratory Diagnosis: Typical requres demonstation of virus in tissue with tissue. May be detected in asymptomatic carrier/shedding states. Histologically, cytomegalic
cells are seen by hematoxyline-eosin staining. These are enlarged cells with a dense,
central, basophilic intranuclear inclusion body often referred to as an “owl’s
eye”. Detection of the viral genome can be achieved through PCR of blood,
biopsy, or urine samples. Serology for IgM antibody can also be used to
demonstrate infection but is not generally clinically used.
Disease manifestations: The clinical manifestations are
highly dependent on the population that is infected. In immunocompetent
patients, the majority are asymptomatic; however, some may present with fever
of unknown origin or mononucleosis (heterophile negative). Congenital infection, especially if the
woman acquires the infection for the first time during pregnancy, can result in
a severe disease called cytomegalic inclusion disease, which is characterized
by intrauterine growth restriction, microcephaly, intracerebral calcifications,
hepatosplenomegaly, thrombocytopenia, jaundice, and rash. Hearing and vision
loss, mental retardation, and stillbirth can also result from congenital
infection. These represent the most severe cases and many neonates are
asymptomatic. Perinatal infection from breastfeeding typically causes no
disease in healthy infants. Immunocompromised patients can have severe and life
threatening diseases including pneumonia, retinitis, colitis, and esophagitis.
In transplant patients, CMV infection can cause organ rejection.
Treatment: Antiviral therapies are mainly for
immunocompromised patients and include ganciclovir, valganciclovir, cidofovir,