The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C
In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlik...
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2021
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oai:doaj.org-article:a2a1a11833e544448897c5ebf5b8b53b2021-11-16T07:36:30ZThe Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C1664-302X10.3389/fmicb.2021.779472https://doaj.org/article/a2a1a11833e544448897c5ebf5b8b53b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.779472/fullhttps://doaj.org/toc/1664-302XIn a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not the coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but no significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a coinfection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.Disha BhangeNityanand PrasadSwati SinghHarshit Kumar PrajapatiShesh Prakash MauryaBindu Parachalil GopalanSowmya NadigDevidas ChaturbhujBoobalan JayaseelanThongadi Ramesh DineshaSyed Fazil AhamedNavneet SinghAnangi BrahmaiahKavita MehtaYuvrajsinh GohilPachamuthu BalakrishnanBimal Kumar DasMary DiasRaman GangakhedkarSanjay MehendaleRamesh S ParanjapeShanmugam SaravananAnita ShetSunil Suhas SolomonSunil Suhas SolomonMadhuri ThakarUdaykumar RangaFrontiers Media S.A.articleHIV-1subtype Cevolutionsequence duplicationlatencyMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
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HIV-1 subtype C evolution sequence duplication latency Microbiology QR1-502 |
| spellingShingle |
HIV-1 subtype C evolution sequence duplication latency Microbiology QR1-502 Disha Bhange Nityanand Prasad Swati Singh Harshit Kumar Prajapati Shesh Prakash Maurya Bindu Parachalil Gopalan Sowmya Nadig Devidas Chaturbhuj Boobalan Jayaseelan Thongadi Ramesh Dinesha Syed Fazil Ahamed Navneet Singh Anangi Brahmaiah Kavita Mehta Yuvrajsinh Gohil Pachamuthu Balakrishnan Bimal Kumar Das Mary Dias Raman Gangakhedkar Sanjay Mehendale Ramesh S Paranjape Shanmugam Saravanan Anita Shet Sunil Suhas Solomon Sunil Suhas Solomon Madhuri Thakar Udaykumar Ranga The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| description |
In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not the coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but no significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a coinfection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy. |
| format |
article |
| author |
Disha Bhange Nityanand Prasad Swati Singh Harshit Kumar Prajapati Shesh Prakash Maurya Bindu Parachalil Gopalan Sowmya Nadig Devidas Chaturbhuj Boobalan Jayaseelan Thongadi Ramesh Dinesha Syed Fazil Ahamed Navneet Singh Anangi Brahmaiah Kavita Mehta Yuvrajsinh Gohil Pachamuthu Balakrishnan Bimal Kumar Das Mary Dias Raman Gangakhedkar Sanjay Mehendale Ramesh S Paranjape Shanmugam Saravanan Anita Shet Sunil Suhas Solomon Sunil Suhas Solomon Madhuri Thakar Udaykumar Ranga |
| author_facet |
Disha Bhange Nityanand Prasad Swati Singh Harshit Kumar Prajapati Shesh Prakash Maurya Bindu Parachalil Gopalan Sowmya Nadig Devidas Chaturbhuj Boobalan Jayaseelan Thongadi Ramesh Dinesha Syed Fazil Ahamed Navneet Singh Anangi Brahmaiah Kavita Mehta Yuvrajsinh Gohil Pachamuthu Balakrishnan Bimal Kumar Das Mary Dias Raman Gangakhedkar Sanjay Mehendale Ramesh S Paranjape Shanmugam Saravanan Anita Shet Sunil Suhas Solomon Sunil Suhas Solomon Madhuri Thakar Udaykumar Ranga |
| author_sort |
Disha Bhange |
| title |
The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| title_short |
The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| title_full |
The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| title_fullStr |
The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| title_full_unstemmed |
The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C |
| title_sort |
evolution of regulatory elements in the emerging promoter-variant strains of hiv-1 subtype c |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/a2a1a11833e544448897c5ebf5b8b53b |
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