title: Human cytomegalovirus UL144 is associated with viremia and infant development sequelae in congenital infection.
abstract: Human cytomegalovirus (HCMV) strains may be genotyped based on polymorphisms that exist within the UL144 gene, which is one of 19 viral genes lost in attenuated laboratory strains. In the present study, UL144 genotypes in congenitally infected babies (congenital cytomegalovirus [cCMV]) were determined, and the relationship between the genotype, viral load, cytokine profile, and patient developmental outcome was investigated. All cCMV infections identified during 2006 and 2007 were included (n = 29). A portion of the infants were clinically assessed at birth and at 12 to 18 months postinfection for cCMV clinical sequelae (n = 18/29). The plasma viral load (PVL) was requested for 23/29 patients, and the UL144 genotype was determined (n = 27/29). The cytokine profile in patient plasma or serum was assessed (n = 20/29). UL144 genotypes A, B, and C were detected within the cCMV population at 33.3%, 29.6%, and 25.9%, respectively. UL144 A and C were associated with a high PVL (P < 0.04). Furthermore, a significant association between the developmental outcome and UL144 A and C was observed (P < 0.04). Only patients infected with UL144 B and A/B were described as having a normal clinical outcome. In addition, a significant correlation between interleukin 10 (IL-10) levels and the PVL was observed (P < 0.04); however, there was no association between the genotype and the cytokine profile. The present study determined that the specific detection of UL144 genotypes A and C was indicative of serious cCMV infection and more likely to lead to long-term cCMV-associated clinical manifestations. The inclusion of HCMV UL144 genotyping along with the recommended PVL monitoring following cCMV diagnosis may aid prediction of the clinical outcome.
authors.affiliation: National Virus Reference Laboratory, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Allison
authors.initials: A
authors.lastname: Waters
authors.forename: Jaythoon
authors.initials: J
authors.lastname: Hassan
authors.forename: Cillian
authors.initials: C
authors.lastname: De Gascun
authors.forename: Ghia
authors.initials: G
authors.lastname: Kissoon
authors.forename: Susan
authors.initials: S
authors.lastname: Knowles
authors.forename: Eleanor
authors.initials: E
authors.lastname: Molloy
authors.forename: Jeff
authors.initials: J
authors.lastname: Connell
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
mesh_terms: D002657:Child Development; D016207:Cytokines / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006803:Human Development; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010949:Plasma / Q000276:immunology / Q000821:virology; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D044967:Serum / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*; D014766:Viremia / Q000821:virology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D008562:Membrane Glycoproteins; C119624:UL144 ORF protein, Human herpesvirus 5; D014764:Viral Proteins; D037521:Virulence Factors
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