Human Cytomegalovirus (CMV)

• Human Cytomegalovirus (CMV) is a double-stranded enveloped linear DNA virus.
• CMV belongs to the Herpesviridae family, specifically the Beta-herpesvirinae subfamily.

General Information

• Infections are typically asymptomatic in adults and children unless they are immunocompromised.
• CMV can remain latent, primarily in monocytes, and reactivate when cell-mediated immunity decreases.
• The virus can persist in the kidneys for years.
• CMV has the largest genome among human herpesviruses.
• Giant cells are formed due to CMV infection.

Symptoms

• Microcephaly is a symptom found in babies infected by CMV (baby’s head is significantly smaller than expected for age).
• Infected babies can have long eyelashes, an upturned nose, distinctive ears, retrognathia (overbite), and a short neck.
• Other symptoms include seizures, deafness, jaundice, and purpura.
• Purpuric lesions resemble a blueberry muffin due to thrombocytopenia.
• Thrombocytopenia and hepatosplenomegaly can also occur.

Impact

• CMV is the leading cause of mental retardation in the U.S.
• Causes congenital abnormalities due to the death of precursor cells.
• It is the most common cause of congenital abnormalities in the U.S.
• Primary infection during the first trimester of pregnancy causes congenital abnormalities.
• Infected infants excrete CMV in urine for several years.

Transmission

• CMV occurs worldwide, and more than 80% of adults have antibodies against it.
• Early in life, CMV transmits across the placenta, within the birth canal, or through breast milk.
• CMV transmits via saliva in young children.
• Later in life, CMV transmits through sexual contact, blood transfusions, or organ transplantation.

Pathogenesis

• Infection of the fetus occurs mainly when a primary CMV infection happens in the pregnant woman.
• Congenital abnormalities are more common when a fetus is infected during the first trimester.
• Infection can cause cytomegalic inclusion disease in fetuses, characterized by multinucleated giant cells with prominent intranuclear inclusions.
• Approximately 20% of infants show clinically apparent manifestations of cytomegalic inclusion disease after being infected with CMV during gestation

Diagnosis

• Histology shows enlarged cytomegalic cells with a dense central "owl's eye”.
• Basophilic intranuclear inclusion bodies are found in any tissue and urine.
• ELISA serological tests can distinguish primary and recurrent infection by demonstrating IgG seroconversion.
• Rapid diagnosis involves detection of viral antigens using immunoassays.
• PCR is a rapid molecular diagnostic test used for tissue biopsy samples, blood, bronchoalveolar lavage, and urine.
• Culture is reliable in immunocompromised patients.

Immune Evasion

• CMV makes the assembly of MHC class I molecule and viral peptide complex unstable.
• Reduces presentation, leading to less recognition for destruction.
• CMV produces microRNAs that target the host cell’s mRNA for class I MHC proteins, preventing their translation.
• CMV infection inhibits the activity of T cells.
• Activity of chemokines are suppressed, thereby preventing immune cells from being recruited to the site of infection.

Diseases in Immunocompromised Patients

• Causes heterophil-negative mononucleosis (fever, lethargy, and abnormal lymphocytes in blood smears).
• Can cause systemic CMV infections, leading to pneumonitis, esophagitis, and hepatitis.
• In AIDS patients, CMV commonly infects the intestinal tract and causes intractable colitis with diarrhea, retinitis, encephalitis, and blindness.
• Responsible for the failure of many kidney transplants.

Treatment

• Treatment is only recommended in immunocompromised patients.
• Ganciclovir is moderately effective for retinitis and pneumonia.
• Valganciclovir is used for treating CMV retinitis.
• Foscarnet is also effective, but it can cause side effects.