title: Intrafamilial transmission of human cytomegalovirus (HCMV): long-term dynamics of epitope-specific antibody response in context of avidity maturation.
abstract: BACKGROUND
  The role of a special early family formation (PEKiP), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented.
  
  
  OBJECTIVE
  To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections.
  
  
  METHODS
  This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT₅₀ values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates.
  
  
  RESULTS
  The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP-meetings.
  
  
  CONCLUSIONS
  PEKiP-meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany. Electronic address: klaus.hamprecht@med.uni-tuebingen.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hamprecht
authors.affiliation: 1st Medical Department, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Alfred Lennart
authors.initials: AL
authors.lastname: Bissinger
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Jose
authors.initials: J
authors.lastname: Arellano-Galindo
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schweinzer
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Xioajing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Göhring
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Mikeler
authors.affiliation: Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D003587:Cytomegalovirus / Q000145:classification* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000635:transmission*; D004279:DNA, Viral / Q000235:genetics; D018562:Disease Transmission, Infectious; D000939:Epitopes / Q000276:immunology; D005192:Family Health; D005260:Female; D005838:Genotype; D005858:Germany; D006801:Humans; D015151:Immunoblotting; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D000939:Epitopes
keywords: Avidity; CMV; Horizontal transmission; Immunoblot; Primary infection; gO sequencing