STEPTRACKERMICROBIOLOGY + HEMATOLOGY + ONCOLOGY | HERPESVIRUSES | HIGH-YIELD REVIEW

Herpesviruses II — EBV, CMV, HHV-6 & HHV-8

The lymphotropic herpesviruses — they cause mononucleosis syndromes, infect transplant and AIDS patients, and two of them drive cancers.

FOCUS ON
EBV binds CD21 on B cells → mononucleosis (fever, exudative pharyngitis, posterior cervical nodes, splenomegaly, atypical CD8⁺ T cells, ⁺ heterophile antibody); rash with amoxicillin; avoid contact sports (splenic rupture). Cancers: Burkitt, Hodgkin, nasopharyngeal carcinoma, post-transplant lymphoproliferative disorder, primary CNS lymphoma in AIDS. CMV: heterophile-negative mono, congenital infection (periventricular calcifications, hearing loss), retinitis in AIDS (CD4 < 50), transplant pneumonitis; owl's-eye inclusions; ganciclovir. HHV-6 → roseola. HHV-8 → Kaposi sarcoma.
DISEASE
VIRUS · MECHANISM
CLINICAL PICTURE
CLUE · TREATMENT
Infectious mononucleosis
EBV via saliva; infects B cells (CD21), CD8⁺ T cells respond
Teens: fever, fatigue, exudative pharyngitis, posterior cervical nodes, hepatosplenomegaly
Atypical lymphocytes · Monospot ⁺ (sheep/horse RBC agglutination) · supportive
Amoxicillin rash
EBV + aminopenicillin (immune reaction, not allergy)
Diffuse maculopapular rash when mono is mistaken for strep
Not true penicillin allergy
Splenic rupture risk
Splenomegaly
Left upper quadrant pain after contact
No contact sports ≥ 3–4 weeks
EBV cancers
Latent proteins (LMP-1, EBNA) drive proliferation
Endemic Burkitt (jaw, Africa), Hodgkin (mixed cellularity), nasopharyngeal carcinoma (southern China), PTLD, AIDS CNS lymphoma
Oral hairy leukoplakia (lateral tongue) in HIV
CMV mononucleosis
CMV via saliva, sex, transfusion, transplant
Fever, fatigue, little pharyngitis or adenopathy
Heterophile negative
Congenital CMV
Most common congenital infection
Periventricular calcifications, microcephaly, sensorineural hearing loss, chorioretinitis, petechiae ("blueberry muffin")
Toxoplasma calcifications are scattered
CMV retinitis
AIDS, CD4 < 50
Painless vision loss; hemorrhage + white exudates ("pizza pie")
Ganciclovir, valganciclovir, foscarnet
CMV in transplant
Reactivation in seropositive donor or recipient, 1–6 months after transplant
Pneumonitis, colitis, esophagitis (linear ulcers), hepatitis, graft dysfunction
Owl's-eye intranuclear inclusions · valganciclovir prophylaxis
Roseola infantum
HHV-6 (HHV-7 less often)
Infant: high fever for days (febrile seizures) → fever breaks → rose-pink rash on trunk
Rash appears as fever ends
Kaposi sarcoma
HHV-8 infects endothelial cells → spindle-cell proliferation
Purple patches, plaques, nodules on skin, mouth, GI tract, lungs in AIDS, transplant, elderly Mediterranean men
Lymphocytic infiltrate · ART, chemotherapy
Other HHV-8 disease
Same virus
Primary effusion lymphoma, multicentric Castleman disease
—

Mechanism — why "atypical lymphocytes" in mono

EBV gp350 binds CD21
→
B cells infectedPolyclonal activation
→
CD8⁺ T cells expandAtypical, large
→
Nodes, spleen, liver enlarge

Polyclonal B-cell activation also makes the heterophile antibodies detected by Monospot.

EBV vs CMV mono

FEATURE
EBV
CMV
Pharyngitis
Prominent, exudative
Mild or absent
Lymphadenopathy
Prominent, posterior
Mild
Heterophile
Positive
Negative
Cell infected
B cell (CD21)
Many (monocytes, epithelia)
Inclusions
None
Owl's-eye

How it's tested

COMMON CONFUSIONBacillary angiomatosis (Bartonella, neutrophils) vs Kaposi sarcoma (HHV-8, lymphocytes, spindle cells) — both purple papules in AIDS.
THE TRAPMonospot can be negative in the first week and in young children — repeat or test EBV-specific antibodies (VCA IgM).
YOUR APPROACHMono syndrome → heterophile → EBV vs CMV. Immunocompromised host → CD4 or transplant timing → CMV organ involvement → ganciclovir family.

If you see… think…

Teen with fever, exudative pharyngitis, posterior nodes, splenomegaly → EBV mono
Rash after amoxicillin for "strep throat" → EBV mono
EBV receptor → CD21
Jaw mass in an African child, starry-sky pattern → Burkitt lymphoma (EBV)
White, corrugated, non-scrapable plaques on lateral tongue in HIV → oral hairy leukoplakia (EBV)
Newborn with periventricular calcifications and hearing loss → congenital CMV
AIDS patient (CD4 30) with painless vision loss → CMV retinitis
Owl's-eye nuclear inclusions → CMV
Infant with days of high fever, then rash as fever breaks → roseola (HHV-6)
Purple nodules on skin and palate in AIDS → Kaposi sarcoma (HHV-8)