bc3c77620cec9c36df5616277c7a6681 302156.pdf 8818fb55d5206828c0d3622f77c2c017b8d22a3a 302156.pdf facc391a186c80277c8c43dd5d37afe70fdefa2d63cd6dff0c0d2134e0127bdc 302156.pdf Title: Targeting Viral Transcription for HIV Cure Strategies Subject: Combination antiretroviral therapy (ART) suppresses viral replication to undetectable levels, reduces mortality and morbidity, and improves the quality of life of people living with HIV (PWH). However, ART cannot cure HIV infection because it is unable to eliminate latently infected cells. HIV latency may be regulated by different HIV transcription mechanisms, such as blocks to initiation, elongation, and post-transcriptional processes. Several latency-reversing (LRA) and -promoting agents (LPA) have been investigated in clinical trials aiming to eliminate or reduce the HIV reservoir. However, none of these trials has shown a conclusive impact on the HIV reservoir. Here, we review the cellular and viral factors that regulate HIV-1 transcription, the potential pharmacological targets and genetic and epigenetic editing techniques that have been or might be evaluated to disrupt HIV-1 latency, the role of miRNA in post-transcriptional regulation of HIV-1, and the differences between the mechanisms regulating HIV-1 and HIV-2 expression. Keywords: viral persistence; HIV; HIV transcription; HIV nuclear export; HIV latency; latency-reversing agents; latency-promoting agents Author: Jon Izquierdo-Pujol, Maria C. Puertas, Javier Martinez-Picado and Sara Morón-López Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Apr 8 11:52:31 2024 CEST ModDate: Mon Apr 8 11:58:30 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1397194 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 DZTJMI+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 HYAXJS+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 GBRUEG+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 EIFDAO+VnURWPalladioL Type 1 Custom yes yes yes 32 0 SIXRFS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 AOPHAZ+CMSY10 Type 1 Builtin yes yes yes 65 0 QDULQU+EURM10 Type 1 Builtin yes yes yes 70 0 CIIIDK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 88 0 CIIIDL+PalatinoLinotype CID TrueType Identity-H yes yes yes 91 0 CIIIDM+PalatinoLinotype TrueType WinAnsi yes yes no 97 0 CIIIDO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 100 0 CIIIDK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 124 0 CIIIDL+PalatinoLinotype CID TrueType Identity-H yes yes yes 127 0 CIIIDM+PalatinoLinotype TrueType WinAnsi yes yes no 133 0 CIIIDO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 CIIJAK+PalatinoLinotype TrueType MacRoman yes yes no 139 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-12-20 02:48:07 CET RepresentationInformation: 302156.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-19 09:44:07 CET Size: 1397194 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 612 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Cellular and Viral Factors Regulating HIV Transcription and Nuclear Export Destination: section.2 Children: Item: Title: Initiation Destination: subsection.2.1 Item: Title: Elongation Destination: subsection.2.2 Item: Title: Polyadenylation Destination: subsection.2.3 Item: Title: Multiple Splicing Destination: subsection.2.4 Item: Title: Nuclear Export Destination: subsection.2.5 Item: Title: Repressive Transcriptional Factors Destination: subsection.2.6 Item: Title: Pharmacological Disruption of HIV Transcription and Nuclear Export Destination: section.3 Item: Title: Genetic and Epigenetic Modulation to Impact HIV Transcription Destination: section.4 Item: Title: What Can We Learn from HIV-2? Destination: section.5 Item: Title: Conclusions Destination: section.6 Item: Title: References Destination: section.7 Info: Title: Targeting Viral Transcription for HIV Cure Strategies Author: Jon Izquierdo-Pujol, Maria C. Puertas, Javier Martinez-Picado and Sara Morón-López Subject: Combination antiretroviral therapy (ART) suppresses viral replication to undetectable levels, reduces mortality and morbidity, and improves the quality of life of people living with HIV (PWH). However, ART cannot cure HIV infection because it is unable to eliminate latently infected cells. HIV latency may be regulated by different HIV transcription mechanisms, such as blocks to initiation, elongation, and post-transcriptional processes. Several latency-reversing (LRA) and -promoting agents (LPA) have been investigated in clinical trials aiming to eliminate or reduce the HIV reservoir. However, none of these trials has shown a conclusive impact on the HIV reservoir. Here, we review the cellular and viral factors that regulate HIV-1 transcription, the potential pharmacological targets and genetic and epigenetic editing techniques that have been or might be evaluated to disrupt HIV-1 latency, the role of miRNA in post-transcriptional regulation of HIV-1, and the differences between the mechanisms regulating HIV-1 and HIV-2 expression. 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Link Rect: 316, 730, 352, 741 Annotation: Subtype: Link Rect: 59, 696, 96, 706 Checksum: 15d19eb9 Type: CRC32 Checksum: bc3c77620cec9c36df5616277c7a6681 Type: MD5 Checksum: 8818fb55d5206828c0d3622f77c2c017b8d22a3a Type: SHA-1 Checksum: facc391a186c80277c8c43dd5d37afe70fdefa2d63cd6dff0c0d2134e0127bdc Type: SHA-256