i) Role of RNPs and ACDs in HIV-1 replication
Following HIV-1 infection, the host cell responds by mounting a robust, anti-viral immune response in order to create an inhospitable environment for viral replication. During a stress response, cells initiate both the shut-off of protein synthesis and the assembly of stress granules (SG). SG are translationally silent ribonucleoproteins (RNPs) and serve as storage sites of mRNAs and proteins. Importantly, many viruses counter this innate immune response using a variety of strategies. Recent work has revealed that eEF2 depletion impaired the SG blockade mediated by HIV-1 and resulted in decreased virus production and infectivity, we propose that anticancer drugs (ACDs) that promote SG assembly in HIV-1 expressing cells represent an innovative avenue of anti-viral therapeutics
ii) Awakening HIV-1: Reactivation of HIV-1 latency
One of the major challenges for the cure of HIV-1 infection is the persistence of proviral genomes in CD4 + T lymphocytes. Specific approaches are being sought to reverse latency and use immunological mechanisms to eradicate persistent infection. HIV-1 Latency Reversing Agents (LRAs) are small molecules capable of modulating the pathways that control HIV-1 latency and are the first target molecules in this effort. Isoflavonoids represent a class of potentially useful components to counteract HIV-1 infection.
iii) RNAstasis during HIV-1 replication
mRNPs are assembled immediately after the nascent transcript emerges following transcription of DNA and are remodeled by co-transcriptional RNA-processing reactions. After a cellular mRNA reaches the translation machinery, it will undergo degradation as a way of turnover by the mRNA decay machinery. Indeed, it is suggested that mRNA degradation is tightly dependent on translation. As such, mRNA turnover rates also depend on the specific composition of the given mRNPs, cis-acting elements in mRNA and trans-acting factors that contribute to mRNA regulation decay. However, the history is quite different for viruses, which use the same RNA molecule first as mRNA and then as the packaged genome. Thus, it is not surprising that all viruses in general, have evolved different mechanisms aimed to modulate host RNAstasis with a direct impact in the assembly of different RNA granules while counteracting mRNA decay machineries
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