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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

Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. 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 h...

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Autores principales: Waters, Shelley, Lee, Silvia, Ariyanto, Ibnu, Kresoje, Nina, Leary, Shay, Munyard, Kylie, Gaudieri, Silvana, Irish, Ashley, Keil, Anthony D., Allcock, Richard J. N., Price, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104433/
https://www.ncbi.nlm.nih.gov/pubmed/35563032
http://dx.doi.org/10.3390/ijms23094644
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author Waters, Shelley
Lee, Silvia
Ariyanto, Ibnu
Kresoje, Nina
Leary, Shay
Munyard, Kylie
Gaudieri, Silvana
Irish, Ashley
Keil, Anthony D.
Allcock, Richard J. N.
Price, Patricia
author_facet Waters, Shelley
Lee, Silvia
Ariyanto, Ibnu
Kresoje, Nina
Leary, Shay
Munyard, Kylie
Gaudieri, Silvana
Irish, Ashley
Keil, Anthony D.
Allcock, Richard J. N.
Price, Patricia
author_sort Waters, Shelley
collection PubMed
description Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. 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.
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spelling pubmed-91044332022-05-14 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 Waters, Shelley Lee, Silvia Ariyanto, Ibnu Kresoje, Nina Leary, Shay Munyard, Kylie Gaudieri, Silvana Irish, Ashley Keil, Anthony D. Allcock, Richard J. N. Price, Patricia Int J Mol Sci Article Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. 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. MDPI 2022-04-22 /pmc/articles/PMC9104433/ /pubmed/35563032 http://dx.doi.org/10.3390/ijms23094644 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Waters, Shelley
Lee, Silvia
Ariyanto, Ibnu
Kresoje, Nina
Leary, Shay
Munyard, Kylie
Gaudieri, Silvana
Irish, Ashley
Keil, Anthony D.
Allcock, Richard J. N.
Price, Patricia
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104433/
https://www.ncbi.nlm.nih.gov/pubmed/35563032
http://dx.doi.org/10.3390/ijms23094644
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