Targeting TRIM5α in HIV Cure Strategies for the CRISPR-Cas9 Era

Dav., Weatherley; Boswell, Michael T; Rowland‐Jones, Sarah

doi:10.3389/fimmu.2017.01616

Cited by 7 publications

(7 citation statements)

References 81 publications

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“…One of the first factors targeted by this strategy is TRIM5α, which could be modified to restrict retroviral infection by promoting autophagy against HIV-1, soon after viral entry into the cell (Hatziioannou et al, 2004;Stremlau et al, 2004;Mandell et al, 2014a,b;Richardson et al, 2014;Ribeiro et al, 2016;Saha et al, 2020). Thus, it has been proposed that HSCs harvested from an HIV-positive patient could be transduced with an adeno-associated virus (AAV) vector bearing the Cas9 enzyme together with the single guide RNA (sgRNA) targeting TRIM5α and a repair template to introduce the mutations to target HIV-1 (Weatherley et al, 2017). These transgenic HSCs bearing the mutated TRIM5α would be implanted to achieve long-term cell repopulation in order to generate a durable subset of CD4 + T cells resistant to HIV-1 infection as reported with the CCR5 gene (Xu et al, 2017).…”

Section: The Effect Of Autophagy Modulation In the Early Steps Of Hiv-1 Infectionmentioning

confidence: 99%

The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+ T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.

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Section: The Effect Of Autophagy Modulation In the Early Steps Of Hiv-1 Infectionmentioning

confidence: 99%

The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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“…CRISPR-Cas based targeting of host genes represents an alternative solution for virus related disease treatment for future applications. Weatherley et al predicted an AAV-SaCRISPR-Cas9 mediated ex vivo gene editing of TRIM5α in hematopoietic stem cells (HSCs) to cure HIV [ 230 ]. As an antiviral strategy, gene therapy shows many promising clinical results [ 59 , 231 ], however, financial investment and research efforts must be made for the enhancement of this technology.…”

Section: Discussionmentioning

confidence: 99%

CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy

Chen

Guo

2018

Viruses

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Currently, a new gene editing tool—the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system—is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.

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“…Two specific amino acids in TRIM5 have made it an actual antiviral agent against HIV-1 infection. This antiviral candidate can induce cleavage of viral capsid proteins, demonstrating its antiviral properties (Sastri and Campbell, 2011;Weatherley et al, 2017). Therefore, TRIM5 may be a suitable target for the CRISPR/Cas9 system.…”

Section: Application Of Crispr/cas9 Technology In Current Virologymentioning

confidence: 99%

CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2

Shademan

Nourazarian

Hajazimian

et al. 2022

Front. Mol. Biosci.

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Outbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.

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Targeting TRIM5α in HIV Cure Strategies for the CRISPR-Cas9 Era

Cited by 7 publications

References 81 publications

The Interplay of HIV and Autophagy in Early Infection

The Interplay of HIV and Autophagy in Early Infection

CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy

CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2

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