Abstract
Helicases hydrolyze nucleotide triphosphates (NTPs) and use the energy to modify the structures of nucleic acids. They are key players in every cellular process involving RNA or DNA. Human immunodeficiency virus type 1 (HIV-1) does not encode a helicase, thus it has to exploit cellular helicases in order to efficiently replicate its RNA genome. Indeed, several helicases have been found to specifically associate with HIV-1 and promote viral replication. However, studies have also revealed a couple of helicases that inhibit HIV-1 replication; these findings suggest that HIV-1 can either benefit from the function of cellular helicases or become curtailed by these enzymes. In this review, we focus on what is known about how a specific helicase associates with HIV-1 and how a distinct step of HIV-1 replication is affected. Despite many helicases having demonstrated roles in HIV-1 replication and dozens of other helicase candidates awaiting to be tested, a deeper appreciation of their involvement in the HIV-1 life cycle is hindered by our limited knowledge at the enzymatic and molecular levels regarding how helicases shape the conformation and structure of viral RNA-protein complexes and how these conformational changes are translated into functional outcomes in the context of viral replication.
Highlights
Helicases hydrolyze nucleotide triphosphates (NTPs) and use the energy to modify the structures of nucleic acids
Upf1 associates with the 3′UTR of Human immunodeficiency virus type 1 (HIV-1) RNA HIV-1 RNA has a long 30UTR that represents one of the signals, in addition to the pre-mature termination codon (PTC) and the upstream open reading frame, that are recognized by the nonsense-mediated decay (NMD) machinery [71]
DDX1 and DDX3 are associated with the Rev/RRE/CRM1 complex and regulate viral RNA export [3,38,40]
Summary
Was not recognized until DDX3 was found to participate in the Rev-dependent export of unspliced and partially spliced HIV-1 RNAs [3]. It remains to be further investigated how each of these helicases affects the function of Rev and whether they play redundant roles or are involved in distinct steps of Rev-mediated RNA export These helicases were not reported to associate with Rev in a separate protoemic study that employed the affinity tagging purification and mass spectrometry methods to identify cellular factors that interact with each of the 18 HIV-1 proteins [44]. A further analysis of the viral RNA complex within the RHA-depleted virus particles reveals a reduced level of tRNALys. that is annealed onto the primer binding site (PBS) [52] This latter finding is verified by in vitro study showing that the purified recombinant wild type RHA, but not its helicase-null mutant K417R, assists Gag/NC in promoting the formation of tRNALys.3/viral RNA binary complex [52]. The PCE exists in the 50UTRs of different retroviruses, including
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