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EBV, CMV and varicella serology

15 min

Skills you'll build3 skills
  • Call EBV infection recent or past from VCA IgM, VCA IgG, and EBNA antibody
  • Choose the CMV test for past exposure, current replication, or congenital infection
  • Choose lesion PCR or VZV IgG to tell current infection from past immunity

At the bench: Relate viral serology findings to the stage of infection

Try first

Try first

A young adult's Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgG is reactive at a high value. What does this one result establish?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Dating EBV infection with three antibodies

EBV infects B cells, and the polyclonal B-cell response can produce heterophile antibodies. CDC advises against the rapid heterophile test for general use, because false-positive and false-negative results occur, especially in young children and early illness.1 EBV-specific antibodies are more reliable.

  • VCA IgM appears early and usually disappears within 4 to 6 weeks.
  • VCA IgG appears during the acute illness and persists for life.
  • EBNA antibody appears 2 to 4 months after onset and then persists.1
VCA IgMVCA IgGEBNA antibodyReading
NonreactiveNonreactiveNonreactiveNo past infection
ReactiveReactiveNonreactivePrimary infection
NonreactiveReactiveReactivePast infection

1

A high VCA IgG cannot date the infection. Paired sera add little, because VCA antibodies are often present when the illness starts.1

Choosing a CMV test

Cytomegalovirus (CMV) stays in the body after the first infection and can reactivate. Each test has a different purpose.

  1. Past exposure. CMV IgG. Donor and recipient IgG status determine a transplant's risk group.2
  2. Current replication. Quantitative CMV DNA by nucleic acid amplification test (NAAT) in plasma or whole blood. Serial results are compared only on one specimen type and one assay.2
  3. Congenital infection. Saliva polymerase chain reaction (PCR) within 3 weeks of birth, confirmed with urine PCR. Saliva is collected more than 1 hour after breastfeeding. Antibody testing cannot establish congenital CMV.3

CMV IgG stays reactive after past infection, so it cannot show replication. CMV IgM can persist, return with reactivation or react falsely.3

VZV testing

PCR on material from a skin lesion is the preferred test for current varicella-zoster virus (VZV) infection. Vesicle fluid, scabs and cells from the lesion base are acceptable specimens.4 VZV IgM has poor specificity and cannot separate primary infection from reinfection or reactivation. A reactive VZV IgG shows past varicella or vaccination and cannot confirm a current case.4

Follow the bench demonstration

Sources for this step
References
  1. Centers for Disease Control and Prevention. Laboratory testing for Epstein-Barr virus. April 10, 2024. Accessed September 27, 2026. https://www.cdc.gov/epstein-barr/php/laboratories/index.html
  2. Kotton CN, Kumar D, Manuel O, et al. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025;109(7):1066-1110. doi:10.1097/TP.0000000000005374
  3. Centers for Disease Control and Prevention. Laboratory testing for CMV and congenital CMV. April 15, 2024. Accessed September 27, 2026. https://www.cdc.gov/cytomegalovirus/php/laboratories/index.html
  4. Centers for Disease Control and Prevention. Laboratory testing for varicella-zoster virus. May 10, 2024. Accessed September 27, 2026. https://www.cdc.gov/chickenpox/php/laboratories/index.html

Watch one

Read each decision and its explanation.

A 19-year-old college student has had fever, sore throat and swollen neck nodes for 10 days. His rapid heterophile test was negative. The EBV panel reads:

Does the panel support primary EBV infection?

TestResultReference intervalFlag
EBV VCA IgMReactiveNonreactiveNonreactive
EBV VCA IgGReactiveNonreactiveNonreactive
EBV EBNA antibodyNonreactiveNonreactiveNonreactive

Specimen: H 2, L 8, I 1. Serum

  1. VCA IgG is reactive, so he has been infected at some time.

    VCA IgG shows whether he has ever been infected with EBV, so it is read first.

  2. VCA IgM is reactive, which suggests a recent infection.

    VCA IgM is the early marker that fades within weeks.

  3. EBNA antibody is nonreactive, so the infection is less than about 2 to 4 months old.

    EBNA antibody forms months after onset, so its absence fits a recent infection.

  4. The negative heterophile test does not outweigh the EBV-specific pattern.

    The heterophile test misses cases, especially early in the illness.

Yes. VCA IgM reactive with EBNA antibody nonreactive supports primary EBV infection, and the negative heterophile test does not change that.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A lung transplant recipient is CMV IgG reactive. Her team wants to know whether CMV is replicating now. Which test measures that?

CMV IgG stays reactive after past infection. It cannot show whether the virus is replicating today.

Used CMV IgG to show current replication

CMV IgG remains after past infection, so a reactive IgG cannot show whether the virus is replicating now. Quantitative CMV DNA testing, kept to one specimen type and one assay, measures current replication. Reading IgG as activity can report replication that a DNA test would not find.

CMV DNA in blood measures current replication, and a quantitative result can be followed over time on the same assay.

CMV IgM can persist, return with reactivation or react falsely. It does not measure how much virus is present.

Saliva PCR is the screening test for congenital CMV in a newborn. After a transplant, replication is monitored with CMV DNA in blood.

Hint
  1. Her reactive IgG shows CMV infection at some time.
  2. Sort the options into tests for antibody and tests for virus.

Review Cytomegalovirus

Problem 2 of 3 · Hints available

A 70-year-old man has a band of blisters on one side of his chest. Which specimen and test show current VZV infection?

VZV IgM has poor specificity and can appear in primary infection, reinfection and reactivation. A lesion swab detects the virus directly.

Used VZV IgM to separate primary infection from reactivation

VZV IgM has poor specificity and can appear in primary infection, reinfection, and reactivation, so a positive IgM cannot date the infection. PCR on a lesion swab shows current infection.

VZV IgG shows past infection or vaccination. Most adults his age are IgG reactive whether or not VZV caused this rash.

Lesion PCR detects VZV DNA where the virus is active. It is the preferred test for current infection.

Hint
  1. Serum antibody reflects his whole immune history.
  2. Ask which specimen could contain the virus that is causing this rash.

Review Varicella-zoster virus

Problem 3 of 3 · On your own

A 24-year-old woman has had a sore throat for 1 week. Her results: VCA IgM nonreactive, VCA IgG reactive at a high value, EBNA antibody reactive. How does the panel read?

A high VCA IgG occurs in remote infection too. The reactive EBNA antibody places the infection months or years ago.

Dated EBV infection from a high VCA IgG

VCA IgG appears early and persists for life, and a high value occurs in recent and remote infection alike. Dating infection from it without VCA IgM and EBNA antibody can call a past infection recent.

VCA IgG with EBNA antibody and no VCA IgM fits an infection months or more in the past. EBV is unlikely to explain this week's sore throat.

A reactive VCA IgG shows she has been infected. The other two antibodies date the infection.

Paired EBV sera add little. This single panel already dates the infection.

Review Epstein-Barr virus

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • Dmitri Blank, 52, received a kidney 7 weeks ago.
  • Before transplant he was CMV IgG nonreactive and his donor was CMV IgG reactive.
  • He now has fever. His CMV IgG is reactive today.
  • His earlier CMV DNA results were on plasma with the laboratory's usual assay.
  • Two days later a line of blisters appears on his right flank.
Decision 1 of 3

Does the reactive CMV IgG show that CMV is replicating?

New IgG shows he has now been infected with CMV, which the donor organ could explain. It does not measure replication today.

Used CMV IgG to show current replication

CMV IgG remains after past infection, so a reactive IgG cannot show whether the virus is replicating now. Quantitative CMV DNA testing, kept to one specimen type and one assay, measures current replication. Reading IgG as activity can report replication that a DNA test would not find.

CMV DNA in blood measures the virus now. IgG only shows exposure.

CMV IgM can persist or react falsely. It does not measure replication either.

Review Cytomegalovirus

Decision 2 of 3

Plasma CMV DNA is 4,800 IU/mL. A whole-blood result from an outside laboratory last week was 2,100 IU/mL. How is the change read?

The two results come from different specimen types and assays. Their numbers are not comparable.

Serial CMV DNA results stay on one specimen type and one assay. Compare 4,800 IU/mL with his earlier plasma results.

No fixed conversion exists between specimen types and assays. The outside number cannot be adjusted into this one.

Review Cytomegalovirus

Decision 3 of 3

Which test do you suggest for the flank blisters?

VZV IgM appears in primary infection, reinfection and reactivation. It cannot tell them apart.

Used VZV IgM to separate primary infection from reactivation

VZV IgM has poor specificity and can appear in primary infection, reinfection, and reactivation, so a positive IgM cannot date the infection. PCR on a lesion swab shows current infection.

IgG shows past infection or vaccination. It cannot confirm a current case.

Lesion PCR detects VZV DNA in the rash itself.

Review Varicella-zoster virus

Each question depends on what the test measures. IgG shows past infection with a virus. DNA in blood or in a lesion shows the virus is present now.

For reference

Sources checked