Polymorphisms of the cytomegalovirus (CMV)-encoded tumor necrosis factor-alpha and beta-chemokine receptors in congenital CMV disease.
Some congenital cytomegalovirus (CMV) infections lead to neonatal disease, whereas others have no associated sequelae. To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor (TNF)-alpha-like receptor gene, the US28 beta-chemokine receptor gene, and the UL55 envelope glycoprotein B gene from 33 patients with congenital CMV infection were sequenced. Three major UL144 subtypes (A, B, and C) and 2 recombinants (A/C and A/B) were detected. Infection with the least common UL144 subtypes (A, C, A/C, and A/B) was associated with unfavorable disease outcome (P=.04). There was no association between specific subtypes of the US28 and UL55 genes and outcome (P=.864 and P=.765, respectively). Multiple genotypes (implying multiple infections) were detected in tissues from 8 of 10 autopsies. Therefore, polymorphism in the CMV-encoded TNF-alpha-like receptor appears to be associated with congenital CMV disease. Other CMV polymorphisms should be further evaluated for potential relevance to neonatal infection, transplantation, and acquired immunodeficiency syndrome-associated CMV diseases.
D000595:Amino Acid Sequence; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000401:mortality / Q000635:transmission / Q000821:virology*; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000401:mortality / Q000821:virology*; D018445:Infectious Disease Transmission, Vertical; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D019707:Receptors, Chemokine / Q000737:chemistry / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014774:Virulence
D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; C119624:UL144 ORF protein, Human herpesvirus 5; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins