Human Cytomegalovirus (CMV)

• Human Cytomegalovirus (CMV) is a double-stranded enveloped linear DNA virus.
• It belongs to the Herpesviridae family and Beta-herpesvirinae subfamily.
• CMV infection is usually asymptomatic in adults and children unless immunocompromised.
• The virus remains latent primarily in monocytes and can reactivate when cell-mediated immunity decreases.
• CMV can persist in kidneys for years.

Symptoms

• Microcephaly (smaller than expected head size).
• Long eyelashes, upturned nose, distinctive ears, retrognathia (overbite), and short neck.
• Seizures, deafness, jaundice, purpura (blueberry muffin lesions), thrombocytopenia, hepatosplenomegaly.

Congenital Abnormalities

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

Prevalence

• CMV occurs worldwide, with more than 80% of adults having antibodies.

Diagnosis

• Histology reveals enlarged cytomegalic cells with a dense central "owl's eye," basophilic intranuclear inclusion body in any tissue with urine.
• ELISA can distinguish primary and recurrent infection by demonstrating IgG seroconversion.
• Rapid diagnosis involves viral antigen detection using immunoassays or PCR (for tissue biopsy samples, blood, bronchoalveolar lavage, urine).
• Culture is used in immunocompromised patients.

Treatment

• Treatment is only recommended in immunocompromised patients.
• Ganciclovir shows moderate effectiveness for retinitis and pneumonia.
• Valganciclovir, cidofovir, or fomivirsen treat CMV retinitis.

Immune Evasion Mechanisms

• CMV destabilizes the assembly of MHC class I molecule and viral peptide complex.
• This 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 T cell activity and suppresses chemokine activity, preventing immune cell recruitment.

Impact on Immunocompromised Patients

• Causes heterophil-negative mononucleosis (fever, lethargy, abnormal lymphocytes).
• Can cause systemic CMV infections, including pneumonitis, esophagitis, and hepatitis.
• In AIDS patients, CMV can cause intractable colitis with diarrhea, retinitis, encephalitis, and blindness.
• CMV can lead to failure of kidney transplants.

Viral Characteristics

• CMV has the largest genome among human herpesviruses.
• Giant cells are formed, hence the name cytomegalovirus

Transmission

• CMV is transmitted across the placenta, within the birth canal, or through breast milk.
• Transmission can occur via saliva, sexually, through blood transfusions, or organ transplantation.

Cytomegalic Inclusion Disease

• In fetuses, cytomegalovirus can cause cytomegalic inclusion disease.
• This disease is characterized by multinucleated giant cells with prominent intranuclear inclusions.