Cytomegalovirus Genetic Diversity Following Primary Infection

J Infect Dis. 2020 Feb 18;221(5):715-720. doi: 10.1093/infdis/jiz507.


Background: Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV diversity and changes in diversity over time in healthy adolescent females who participated in a phase 2 CMV gB/MF59 vaccine trial.

Methods: CMV genetic diversity was determined by genotyping of 5 genes-gB (UL55), gH (UL75), gN (UL73), US28, and UL144-in urine, saliva, and plasma samples from 15 study subjects.

Results: At the time of primary infection, 5 of 12 (42%) urine samples had multiple virus strains, and 50% of vaccine recipients were infected with gB1 genotype (vaccine strain). Mixed infection was documented in all 15 subjects within 3 months after primary infection, and the majority had different CMV genotypes in different compartments. Changes in genotypes over time were observed in all subjects.

Conclusions: Infection with multiple CMV genotypes was common during primary infection and further diversification occurred over time. Infection with gB1 genotype in vaccine recipients suggests a lack of strain-specific protection from the vaccine. As only 5 polymorphic genes were assessed, this study likely underestimated the true genetic diversity in primary CMV infection.

Keywords: cytomegalovirus; diversity; primary infection; strains.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Coinfection / diagnosis
  • Coinfection / virology
  • Cytomegalovirus / genetics*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Vaccines / therapeutic use*
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / urine
  • Polymorphism, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Chemokine / blood
  • Receptors, Chemokine / genetics
  • Saliva / virology
  • Vaccination*
  • Viral Envelope Proteins / blood
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / urine
  • Viral Load
  • Viral Proteins / blood
  • Viral Proteins / genetics
  • Viral Proteins / urine


  • Cytomegalovirus Vaccines
  • Membrane Glycoproteins
  • Receptors, Chemokine
  • UL144 ORF protein, Human herpesvirus 5
  • US28 receptor, Cytomegalovirus
  • Viral Envelope Proteins
  • Viral Proteins