Ubiquitous human β-herpesvirus (HHV-5) that establishes lifelong latency; usually asymptomatic or mononucleosis-like in healthy people, but can cause congenital infection (most common congenital virus) and severe opportunistic disease in immunocompromised patients (e.g., retinitis in AIDS). Classic histopathology shows enlarged cells with "owl's eye" intranuclear inclusions.
CMV is the most common congenital viral infection (a leading cause of non-genetic deafness in children) and a major opportunistic pathogen in transplant and HIV/AIDS patients, so recognizing and preventing it is critical.
Healthy individuals: often asymptomatic or a mild mononucleosis-like illness (fever, fatigue, atypical lymphocytes) but with negative heterophile (Monospot) test.
Immunocompromised (e.g., transplant, AIDS): reactivation causes end-organ disease like retinitis (floaters, vision loss, hemorrhagic retinal lesions), esophagitis (odynophagia with large linear ulcers on endoscopy), colitis (diarrhea, abdominal pain), or pneumonitis.
Distinguish EBV vs CMV in mono-like illness: EBV causes heterophile-positive mononucleosis, whereas CMV mononucleosis is heterophile-negative (Monospot test negative).
Confirm congenital CMV by detecting the virus in the infant's saliva or urine within 2–3 weeks of birth (PCR or culture). Newborn hearing test is important, as CMV is a leading cause of infant hearing loss.
In transplant patients, donor/recipient CMV serostatus guides prevention strategy; high-risk patients often receive valganciclovir prophylaxis or frequent monitoring of CMV PCR (DNAemia) with preemptive therapy to prevent disease.
Tissue diagnosis: biopsy of affected tissue (e.g., colon, lung, esophagus) can show characteristic CMV inclusions ("owl's eye" cells) and is the gold standard to confirm invasive disease (often supplemented by immunohistochemistry for CMV).
Condition
Distinguishing Feature
Epstein–Barr virus (EBV)
More common cause of mononucleosis with pharyngitis, lymphadenopathy, and heterophile-positive (Monospot) test
Herpes simplex virus (HSV)
Neonatal HSV is usually acquired during delivery (causing localized lesions or encephalitis, not in utero malformations). In immunosuppressed, HSV can cause esophagitis but typically with small, deep ulcers (vs CMV's large linear ulcers).
Congenital toxoplasmosis
Another TORCH infection; classically causes chorioretinitis, hydrocephalus, and diffuse intracranial calcifications (vs periventricular in CMV)
Congenital rubella
TORCH infection causing deafness, cataracts, and heart defects (PDA); often distinguished by cataracts and no calcifications, plus a similar 'blueberry muffin' rash
No specific therapy needed for immunocompetent patients with mild CMV (supportive care).
Ganciclovir (IV) or valganciclovir (oral) are first-line antivirals for CMV disease in immunocompromised patients and for symptomatic congenital CMV infection (they inhibit viral DNA polymerase).
For ganciclovir-resistant CMV (e.g., due to UL97 mutation): use foscarnet or cidofovir as second-line agents (but they have significant toxicity).
In transplant recipients, valganciclovir is often used prophylactically (or preemptively) to prevent CMV disease in high-risk cases.
Remember "sight-o-megalovirus": CMV retinitis in AIDS (CD4 <50) can cause blindness if not treated (pizza-pie appearance on fundoscopy).
CMV is the C in TORCH infections and the leading cause of congenital viral hearing loss.
Owl's eye inclusions on histology are pathognomonic for CMV (gigantic cells with central intranuclear viral inclusion).
Monospot-negative mononucleosis (heterophile antibody test is negative) in an adult is often due to CMV.
In an immunosuppressed patient, new floaters or visual disturbances → urgent ophthalmologic evaluation for CMV retinitis (to prevent permanent vision loss).
Symptomatic congenital CMV (e.g., seizures, hearing impairment at birth) → start antiviral therapy (e.g., valganciclovir) in the neonatal period to improve neurologic and hearing outcomes.
Suspected mononucleosis → perform heterophile antibody test (Monospot); if negative but clinical suspicion remains, test for CMV IgM to confirm CMV mononucleosis.
Pregnancy: if primary CMV infection is confirmed (seroconversion or IgM positive) or ultrasound shows fetal abnormalities, offer amniocentesis for CMV PCR to diagnose fetal infection. After birth, test newborn's saliva or urine for CMV by PCR/culture within 3 weeks if congenital infection is suspected.
If congenital CMV is confirmed in a symptomatic infant → initiate valganciclovir treatment early (within first month) to improve hearing and developmental outcomes.
Immunocompromised patient with organ-specific symptoms (e.g., retinitis, colitis) → check quantitative CMV DNA PCR in blood and consider tissue biopsy for confirmation. Start ganciclovir (or valganciclovir) promptly if CMV disease is suspected.
HIV/AIDS patient (CD4 count <50) with progressive vision loss and fundoscopic exam showing hemorrhages and fluffy white exudates ("pizza pie" retinopathy) → CMV retinitis; treat with ganciclovir.
Neonate with petechiae, jaundice, hepatosplenomegaly, and periventricular calcifications on head imaging → congenital CMV infection (risk of hearing loss).
College student with prolonged fever and fatigue but negative Monospot test → CMV mononucleosis (heterophile-negative).
Case 1
A 2-week-old newborn presents with jaundice, a diffuse petechial rash, and microcephaly.
Lung tissue histology showing a CMV-infected cell with a large "owl's eye" intranuclear inclusion.
