title: Combined genetic variants of human cytomegalovirus envelope glycoproteins as congenital infection markers.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) is still considered to be the main viral cause of birth defects and long-term neurological and sensory sequelae following congenital infection. Several Authors sustain a key role of HCMV envelope glycoproteins, such as gB, gN and gO - mainly involved in cell targeting, viral penetration and spread - as putative virulence factors. The genes coding for these glycoproteins possess hypervariable regions, resulting in a number of genetic variants in circulating clinical strains. Considering that the genetic polymorphisms underlying the specific differences between gB, gN and gO genotypes can influence the ability of HCMV to preferentially target specific host cells, it is very likely that they play an important role in defining HCMV infection outcome. In the present study, we analysed HCMV gB, gN and gO gene polymorphisms in viral strains isolated from paediatric patients with congenital or post-natal infection, to investigate whether specific genetic variants may be associated with congenital infection.
  
  
  METHODS
  The restriction fragment polymorphisms of genes coding for HCMV gB (UL55), gN (UL73) and gO (UL74) were investigated by analysing viral DNA extracted from 40 urine samples of as many paediatric patients with congenital or post-natal HCMV infection. Randomly selected samples were subjected to DNA sequencing and phylogenetic analysis. Statistical analysis was performed using Fisher's exact test to assess the significance of single and combined glycoprotein genotypes frequency distribution. Statistical significance was considered at a P <0.05.
  
  
  RESULTS
  While gB genomic variants were quite homogeneously represented in both paediatric groups, the gN4 genotype significantly prevailed in congenitally infected children (89.5 %) vs post-natally infected children (47.6 %), with a predominance of the gN4c variant (47.4 %). A similar trend was observed for gO3 (52.6 % vs 19 %). Concerning genotypes association, a statistically significant (P = 0.037) gN4-gO3 combination was found specifically in the congenitally infected group.
  
  
  CONCLUSIONS
  The results indicate that the gN4 (mostly the gN4c variant) and gO3 combined genotypes could provide useful markers of congenital infection and represent suitable candidate molecules for prophylactic vaccine preparations.
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. mariacristina.arcangeletti@unipr.it.
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Arcangeletti
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. rosita.vasilesimone@studenti.unipr.it.
authors.forename: Rosita
authors.initials: R
authors.lastname: Vasile Simone
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. isabella.rodighiero@ao.pr.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Rodighiero
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. flora.deconto@unipr.it.
authors.forename: Flora
authors.initials: F
authors.lastname: De Conto
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. mariacristina.medici@unipr.it.
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Medici
authors.affiliation: Unit of Molecular Genetics, University-Hospital of Parma, Parma, Italy. dmartorana@ao.pr.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. carlo.chezzi@unipr.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Chezzi
authors.affiliation: Unit of Microbiology and Virology - Department of Clinical and Experimental Medicine, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy. adriana.calderaro@unipr.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Calderaro
mesh_terms: D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000821:virology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014556:Urine / Q000821:virology; D015678:Viral Structural Proteins / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D006023:Glycoproteins; D015678:Viral Structural Proteins; D037521:Virulence Factors