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Perspectives of Genome-Editing Technologies for HIV Therapy

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ABSTRACT

Background: Current HIV antiretroviral therapies potently suppress virus replication and prevent patients from progressing to AIDS but are unable to completely eliminate HIV due to the existence of dormant viral reservoirs which threaten to reemerge at anytime. Recently, genome-editing technologies that can recognize specific DNA sequences, including viral DNA, are being touted as promising tools for curing HIV, owing to their specificity, ease of use, and ability to be custom designed.

Conclusion: Here, we introduce several novel strategies aimed at eradicating HIV proviruses with state-of-the-art genome-editing technologies and discuss perspectives of these approaches for curing HIV.

No MeSH data available.


Related in: MedlinePlus

Inhibition of HIV replication with anti-HIV nuclease. HIV cDNA is proposed to be integrated at the host genome interacting with nuclear pore complex immediately after nuclear import. If HIV cDNA is cleaved before integration, HIV replication can be inhibited. But if anti-HIV nuclease cleaves HIV cDNA after integration, the integrated provirus produces viruses until it is digested.
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Figure 3: Inhibition of HIV replication with anti-HIV nuclease. HIV cDNA is proposed to be integrated at the host genome interacting with nuclear pore complex immediately after nuclear import. If HIV cDNA is cleaved before integration, HIV replication can be inhibited. But if anti-HIV nuclease cleaves HIV cDNA after integration, the integrated provirus produces viruses until it is digested.

Mentions: Interestingly, constitutively expressed nucleases cleave unintegrated HIV DNA and protect against new HIV infection [31, 32]. These results suggested that the HIV provirus is cleaved before integration in the nucleus when the anti-HIV nuclease system is installed and functioning. However, a very recent study reported that the HIV cDNA is integrated at the genomic locus associating with the nuclear pore complex [33], meaning that immediate integration of HIV cDNA can occur after nuclear transport. Therefore, it is quite unlikely that the inhibition of the majority of HIV provirus occurs through cleavage before integration and, if so, complete inhibition of HIV replication via nucleases may be difficult to achieve (Fig. 3). Further studies are necessary to uncover whether the pre-transduction of the anti-viral nuclease provides resistance for HIV replication.


Perspectives of Genome-Editing Technologies for HIV Therapy
Inhibition of HIV replication with anti-HIV nuclease. HIV cDNA is proposed to be integrated at the host genome interacting with nuclear pore complex immediately after nuclear import. If HIV cDNA is cleaved before integration, HIV replication can be inhibited. But if anti-HIV nuclease cleaves HIV cDNA after integration, the integrated provirus produces viruses until it is digested.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384355&req=5

Figure 3: Inhibition of HIV replication with anti-HIV nuclease. HIV cDNA is proposed to be integrated at the host genome interacting with nuclear pore complex immediately after nuclear import. If HIV cDNA is cleaved before integration, HIV replication can be inhibited. But if anti-HIV nuclease cleaves HIV cDNA after integration, the integrated provirus produces viruses until it is digested.
Mentions: Interestingly, constitutively expressed nucleases cleave unintegrated HIV DNA and protect against new HIV infection [31, 32]. These results suggested that the HIV provirus is cleaved before integration in the nucleus when the anti-HIV nuclease system is installed and functioning. However, a very recent study reported that the HIV cDNA is integrated at the genomic locus associating with the nuclear pore complex [33], meaning that immediate integration of HIV cDNA can occur after nuclear transport. Therefore, it is quite unlikely that the inhibition of the majority of HIV provirus occurs through cleavage before integration and, if so, complete inhibition of HIV replication via nucleases may be difficult to achieve (Fig. 3). Further studies are necessary to uncover whether the pre-transduction of the anti-viral nuclease provides resistance for HIV replication.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Current HIV antiretroviral therapies potently suppress virus replication and prevent patients from progressing to AIDS but are unable to completely eliminate HIV due to the existence of dormant viral reservoirs which threaten to reemerge at anytime. Recently, genome-editing technologies that can recognize specific DNA sequences, including viral DNA, are being touted as promising tools for curing HIV, owing to their specificity, ease of use, and ability to be custom designed.

Conclusion: Here, we introduce several novel strategies aimed at eradicating HIV proviruses with state-of-the-art genome-editing technologies and discuss perspectives of these approaches for curing HIV.

No MeSH data available.


Related in: MedlinePlus