Sequencing of the Viral UL111a Gene Directly from Clinical Specimens Reveals Variants of HCMV-Encoded IL-10 That Are Associated with Altered Immune Responses to HCMV
MetadataShow full item record
Funding and Sponsorship
Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults world-wide. Acute infections are often asymptomatic in healthy individuals but generate diverse syndromes in neonates, renal transplant recipients (RTR), and people with HIV (PWH). The HCMV gene UL111a encodes a homolog of human interleukin-10 (IL-10) that interacts with the human IL-10 receptor. Deep sequencing technologies were used to sequence UL111a directly from 59 clinical samples from Indonesian PWH and Australian RTR, healthy adults, and neonates. Overall, 93% of samples contained more than one variant of HCMV, as defined by at least one nonsynonymous variation. Carriage of these variants differed between neonates and adults, Australians and Indonesians, and between saliva and blood leukocytes. The variant alleles of N41D and S71Y occurred together in Australian RTR and were associated with higher T-cell responses to HCMV pp65. The variant P122S was associated with lower levels of antibodies reactive with a lysate of HCMV-infected fibroblasts. L174F was associated with increased levels of antibodies reactive with HCMV lysate, immediate-early 1 (IE-1), and glycoprotein B (gB) in Australian RTR and Indonesians PWH, suggesting a higher viral burden. We conclude that variants of UL111a are common in all populations and may influence systemic responses to HCMV.
Showing items related by title, author, creator and subject.
Sequencing directly from clinical specimens reveals genetic variations in HCMV-encoded chemokine receptor us28 that may influence antibody levels and interactions with human chemokinesWaters, Shelley ; Agostino, Mark ; Lee, S.; Ariyanto, I.; Kresoje, N.; Leary, S.; Munyard, Kylie ; Gaudieri, S.; Gaff, J.; Irish, A.; Keil, A.D.; Price, Patricia ; Allcock, R.J.N. (2021)Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by;80% of the world’s population. Acute infections are asymptomatic in healthy individuals but generate diverse syndromes in neonates, solid organ transplant ...
Whole-exome sequencing in multiplex preeclampsia families identifies novel candidate susceptibility genesMelton, Phillip; Johnson, M.; Gokhale-Agashe, D.; Rea, A.; Ariff, A.; Cadby, G.; Peralta, J.; Mcnab, T.; Allcock, R.; Abraham, L.; Blangero, J.; Brennecke, S.; Moses, E. (2019)OBJECTIVE: Preeclampsia is a common and serious heritable disorder of human pregnancy. Although there have been notable successes in identification of maternal susceptibility genes a large proportion of the heritability ...
McCarthy, N.; Melton, P.; Ward, S.; Allan, S.; Dragovic, M.; Clark, M.; Morar, B.; Rubio, J.; Blangero, J.; Badcock, J.; Morgan, V.; Moses, Eric; Jablensky, A. (2016)The exome array assays rare-but-recurrent, likely deleterious, exonic variants and represents an intermediary between single nucleotide polymorphism (SNP) arrays and sequencing for genetic association studies. Multiplex ...