scholarly journals The Splice of Life: Does RNA Processing Have a Role in HIV-1 Persistence?

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1751
Author(s):  
Alexander O. Pasternak ◽  
Ben Berkhout
Keyword(s):  
Antiretroviral Therapy ◽  
Rna Processing ◽  
Viral Rna ◽  
Clinical Implications ◽  
Virus Persistence ◽  
Main Obstacle ◽  
Hiv 1

Antiretroviral therapy (ART) suppresses HIV-1 replication but does not eradicate the virus. Persistence of HIV-1 latent reservoirs in ART-treated individuals is considered the main obstacle to achieving an HIV-1 cure. However, these HIV-1 reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. HIV-1 latency is regulated at the transcriptional and at multiple post-transcriptional levels. Here, we review recent insights into the possible contribution of viral RNA processing to the persistence of HIV-1 reservoirs, and discuss the clinical implications of persistence of viral RNA species in ART-treated individuals.

scholarly journals Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS

2009 ◽  
Vol 84 (6) ◽  
pp. 2913-2922 ◽  
Author(s):  
Thomas W. North ◽  
Joanne Higgins ◽  
Jesse D. Deere ◽  
Timothy L. Hayes ◽  
Andradi Villalobos ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Nonhuman Primate ◽  
Highly Active Antiretroviral Therapy ◽  
Comprehensive Analysis ◽  
Viral Rna ◽  
Organ Distribution ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Highly Active ◽  
Hiv 1

ABSTRACT Highly active antiretroviral therapy (HAART) enables long-term suppression of plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds following cessation of therapy. During HAART, this virus resides in latently infected cells, such as resting CD4+ T cells, and in other cell types that may support residual virus replication. Therapeutic eradication will require elimination of virus from all reservoirs. We report here a comprehensive analysis of these reservoirs in fluids, cells, and tissues in a rhesus macaque model that mimics HAART in HIV-infected humans. This nonhuman primate model uses RT-SHIV, a chimera of simian immunodeficiency virus containing the HIV-1 reverse transcriptase (RT). Methods were developed for extraction, preamplification, and real-time PCR analyses of viral DNA (vDNA) and viral RNA (vRNA) in tissues from RT-SHIV-infected macaques. These methods were used to identify viral reservoirs in RT-SHIV-infected macaques treated with a potent HAART regimen consisting of efavirenz, emtricitabine, and tenofovir. Plasma virus loads at necropsy ranged from 11 to 28 copies of vRNA per ml. Viral RNA and DNA were detected during HAART, in tissues from numerous anatomical locations. Additional analysis provided evidence for full-length viral RNA in tissues of animals with virus suppressed by HAART. The highest levels of vDNA and vRNA in HAART-treated macaques were in lymphoid tissues, particularly the spleen, lymph nodes, and gastrointestinal tract tissues. This study is the first comprehensive analysis of the tissue and organ distribution of a primate AIDS virus during HAART. These data demonstrate widespread persistence of residual virus in tissues during HAART.

scholarly journals An activator of G protein-coupled receptor and MEK1/2-ERK1/2 signaling inhibits HIV-1 replication by altering viral RNA processing

2020 ◽  
Vol 16 (2) ◽  
pp. e1008307 ◽  
Author(s):  
Raymond W. Wong ◽  
Ahalya Balachandran ◽  
Peter K. Cheung ◽  
Ran Cheng ◽  
Qun Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Rna Processing ◽  
Viral Rna ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Hiv 1

scholarly journals Characterization of novel inhibitors of HIV-1 replication that function via alteration of viral RNA processing and rev function

2013 ◽  
Vol 41 (20) ◽  
pp. 9471-9483 ◽  
Author(s):  
Raymond W. Wong ◽  
Ahalya Balachandran ◽  
Matthew Haaland ◽  
Peter Stoilov ◽  
Alan Cochrane
Keyword(s):  
Rna Processing ◽  
Viral Rna ◽  
Hiv 1

scholarly journals Digoxin Suppresses HIV-1 Replication by Altering Viral RNA Processing

2013 ◽  
Vol 9 (3) ◽  
pp. e1003241 ◽  
Author(s):  
Raymond W. Wong ◽  
Ahalya Balachandran ◽  
Mario A. Ostrowski ◽  
Alan Cochrane
Keyword(s):  
Rna Processing ◽  
Viral Rna ◽  
Hiv 1

scholarly journals HIV-1 Viremia Not Suppressible By Antiretroviral Therapy Can Originate from Large T-Cell Clones Producing Infectious Virus

2020 ◽  
Author(s):  
Elias K. Halvas ◽  
Kevin W. Joseph ◽  
Leah D. Brandt ◽  
Shuang Guo ◽  
Michele D. Sobolewski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Medication Adherence ◽  
Antiretroviral Therapy ◽  
Cultured Cells ◽  
Integration Site ◽  
Viral Rna ◽  
Rna Sequences ◽  
Genomic Rnas ◽  
Proviral Integration Site ◽  
Hiv 1

AbstractBACKGROUNDHIV-1 viremia that is not suppressed by combination antiretroviral therapy (ART) is generally attributed to incomplete medication adherence and/or drug resistance. We evaluated individuals referred for non-suppressible viremia (plasma HIV-1 RNA above 40 copies/ml) who reported adherence to ART and did not show drug resistance to their current regimen.METHODSSamples were collected from at least two time points from eight donors who had non-suppressible viremia for more than six months on ART. Single templates of HIV-1 RNA obtained from plasma and viral outgrowth of cultured cells and from proviral DNA were PCR-amplified and sequenced for evidence of clones of cells that produced infectious viruses. Clones were identified by host-proviral integration site analysis.RESULTSHIV-1 genomic RNAs with identical sequences were identified in plasma samples from all eight donors. The identical viral RNA sequences did not change over time and lacked resistance to the ART regimen. In four of the donors, viral RNA sequences obtained from plasma matched those sequences from viral outgrowth cultures, indicating that the viruses were replication-competent. Integration sites for infectious proviruses from those four donors were mapped to introns of the MATR3, ZNF268, ZNF721/ABCA11P, and ABCA11P genes. The sizes of the clones were from 50 million to 350 million cells.CONCLUSIONClones of HIV-1-infected cells producing virus can cause failure of ART to suppress viremia despite medication adherence and absence of drug resistance. The mechanisms involved in clonal expansion and persistence need to be defined to eliminate viremia and the HIV-1 reservoir.

Treatment as prevention: a replication study on early antiretroviral therapy initiation and HIV-1 transmission

2020 ◽  
Author(s):  
Eric W Djimeu ◽  
◽  
Eleanor G Dickens ◽  
Keyword(s):  
Antiretroviral Therapy ◽  
Replication Study ◽  
Treatment As Prevention ◽  
Therapy Initiation ◽  
Hiv 1
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