Polymorphisms of the Cytomegalovirus (CMV)–Encoded Tumor Necrosis Factor–α and β-Chemokine Receptors in Congenital CMV Disease

• Published in: The Journal of infectious diseases Vol. 186; no. 8; pp. 1057 - 1064
• Main Authors: Arav-Boger, Ravit, Willoughby, Rodney E., Pass, Robert F., Zong, Jian-Chao, Jang, Won-Jong, Alcendor, Donald, Hayward, Gary S.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.10.2002; University of Chicago Press
• Subjects: Amino Acid Sequence; Autopsies; Biological and medical sciences; Cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus - pathogenicity; Cytomegalovirus infections; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - mortality; Cytomegalovirus Infections - transmission; Cytomegalovirus Infections - virology; DNA; Female; Fetus; Genes, Viral - genetics; Genotype; Genotypes; Human viral diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases - mortality; Infant, Newborn, Diseases - virology; Infants; Infections; Infectious Disease Transmission, Vertical; Infectious diseases; Major Articles; Medical sciences; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Miscellaneous; Molecular Sequence Data; Phylogeny; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Pregnancy; Receptors, Chemokine - chemistry; Receptors, Chemokine - genetics; Receptors, Tumor Necrosis Factor - chemistry; Receptors, Tumor Necrosis Factor - genetics; Tissue samples; Viral diseases; Viral Proteins - chemistry; Viral Proteins - genetics; Virulence; Human; Pathogenesis; Herpesviridae; Clinical form; Betaherpesvirinae; Genetic determinism; Congenital disease; Human cytomegalovirus; Infection; Virus; Newborn; Gene; Tumor necrosis factor β; Tumor necrosis factor α; Polymorphism; Biological receptor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/344238

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)–α–like receptor gene, the US28 β-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-α–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