Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy
HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term A...
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2025-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/17/7/961 |
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| author | Jenna M. Hasson Mary Grace Katusiime Adam A. Capoferri Michael J. Bale Brian T. Luke Wei Shao Mark F. Cotton Gert van Zyl Sean C. Patro Mary F. Kearney |
| author_facet | Jenna M. Hasson Mary Grace Katusiime Adam A. Capoferri Michael J. Bale Brian T. Luke Wei Shao Mark F. Cotton Gert van Zyl Sean C. Patro Mary F. Kearney |
| author_sort | Jenna M. Hasson |
| collection | DOAJ |
| description | HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the <i>env</i> gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the <i>env</i> gene, >80% contained two or more defects, most commonly stop codons and/or <i>gag</i> start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and <i>tat</i> was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children. |
| format | Article |
| id | doaj-art-3e832ea785c04cf5b41a7cf8a531b51d |
| institution | Matheson Library |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-3e832ea785c04cf5b41a7cf8a531b51d2025-07-25T13:38:58ZengMDPI AGViruses1999-49152025-07-0117796110.3390/v17070961Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral TherapyJenna M. Hasson0Mary Grace Katusiime1Adam A. Capoferri2Michael J. Bale3Brian T. Luke4Wei Shao5Mark F. Cotton6Gert van Zyl7Sean C. Patro8Mary F. Kearney9HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USAFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USADivision of Medical Virology, Department of Pathology, Stellenbosch University, Cape Town 7500, South AfricaDivision of Medical Virology, Department of Pathology, Stellenbosch University, Cape Town 7500, South AfricaFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAHIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the <i>env</i> gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the <i>env</i> gene, >80% contained two or more defects, most commonly stop codons and/or <i>gag</i> start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and <i>tat</i> was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children.https://www.mdpi.com/1999-4915/17/7/961HIV in childrenHIV reservoirHIV persistenceHIV provirusesHIV latencyintact provirus |
| spellingShingle | Jenna M. Hasson Mary Grace Katusiime Adam A. Capoferri Michael J. Bale Brian T. Luke Wei Shao Mark F. Cotton Gert van Zyl Sean C. Patro Mary F. Kearney Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy Viruses HIV in children HIV reservoir HIV persistence HIV proviruses HIV latency intact provirus |
| title | Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy |
| title_full | Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy |
| title_fullStr | Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy |
| title_full_unstemmed | Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy |
| title_short | Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy |
| title_sort | differential hiv 1 proviral defects in children vs adults on antiretroviral therapy |
| topic | HIV in children HIV reservoir HIV persistence HIV proviruses HIV latency intact provirus |
| url | https://www.mdpi.com/1999-4915/17/7/961 |
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