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 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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MDPI
2022
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1068652 http://hdl.handle.net/20.500.11937/89466 |
| _version_ | 1848765226520936448 |
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| author | Waters, Shelley Lee, S. Ariyanto, I. Kresoje, N. Leary, S. Munyard, Kylie Gaudieri, S. Irish, A. Keil, A.D. Allcock, R.J.N. Price, Patricia |
| author_facet | Waters, Shelley Lee, S. Ariyanto, I. Kresoje, N. Leary, S. Munyard, Kylie Gaudieri, S. Irish, A. Keil, A.D. Allcock, R.J.N. Price, Patricia |
| author_sort | Waters, Shelley |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:31:53Z |
| format | Journal Article |
| id | curtin-20.500.11937-89466 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:31:53Z |
| publishDate | 2022 |
| publisher | MDPI |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-894662022-11-02T04:01:24Z 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, S. Ariyanto, I. Kresoje, N. Leary, S. Munyard, Kylie Gaudieri, S. Irish, A. Keil, A.D. Allcock, R.J.N. Price, Patricia Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry human cytomegalovirus interleukin-10 UL111a renal transplant recipients people with HIV deep sequencing HUMAN CYTOMEGALOVIRUS TRANSPLANT RECIPIENTS HUMAN INTERLEUKIN-10 HIV PATIENTS HOMOLOG HEALTH CMV SEROPREVALENCE ANTIBODIES MUTATIONS 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. 2022 Journal Article http://hdl.handle.net/20.500.11937/89466 10.3390/ijms23094644 English http://purl.org/au-research/grants/nhmrc/1068652 http://creativecommons.org/licenses/by/4.0/ MDPI fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry human cytomegalovirus interleukin-10 UL111a renal transplant recipients people with HIV deep sequencing HUMAN CYTOMEGALOVIRUS TRANSPLANT RECIPIENTS HUMAN INTERLEUKIN-10 HIV PATIENTS HOMOLOG HEALTH CMV SEROPREVALENCE ANTIBODIES MUTATIONS Waters, Shelley Lee, S. Ariyanto, I. Kresoje, N. Leary, S. Munyard, Kylie Gaudieri, S. Irish, A. Keil, A.D. Allcock, R.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 | Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry human cytomegalovirus interleukin-10 UL111a renal transplant recipients people with HIV deep sequencing HUMAN CYTOMEGALOVIRUS TRANSPLANT RECIPIENTS HUMAN INTERLEUKIN-10 HIV PATIENTS HOMOLOG HEALTH CMV SEROPREVALENCE ANTIBODIES MUTATIONS |
| url | http://purl.org/au-research/grants/nhmrc/1068652 http://hdl.handle.net/20.500.11937/89466 |