Omain of the protein contains a nuclear export signal (NES), which
Omain of the protein contains a nuclear export signal (NES), which is masked in the fulllength protein and is functional when the C-terminal domain is deleted [35]. We previously have demonstrated that an ectopically expressed dominant negative mutant of INI1, termed S6, containing the minimal IN-interaction domain potentlyinhibits HIV-1 assembly and particle production [22]. This inhibition was mediated by binding of S6 to IN within the context of Gag-Pol. These results suggested that the effect of dominant negative mutant of INI1 may mimic the effect of pleiotropic IN mutants and that the interaction of INI1 with Gag-Pol is required for efficient assembly and particle production. We have found that INI1 itself is specifically incorporated into HIV-1 virions and the microvescicles are devoid of this cellular protein [36]. Furthermore, incorporation of INI1 is restricted to HIV-1 and it is not found in other closely PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28298493 related primate lentiviruses such as HIV-2, SIV-1agm or HTLV-1 and other onco-retroviruses such as Mo-MLV [36]. This restrictive incorporation of INI1 into HIV-1 is correlated to the specific interaction of the protein with HIV-1 IN but not with other H 4065 site retroviral integrases. Furthermore, S6, the trasndominant mutant derived from INI1, did not affect the particle production of other related primate lentiviruses and Mo-MLV, consistent with the idea that interaction of S6 with IN is a prerequisite for its inhibitory effect. Recent immuno-precipitation studies indicated that INI1 is also a part of pre-integration and reverse transcription complexes [37]. A recent study using the siRNA mediated knock-down of INI1, specifically in the target cells (but not in the producer cells) reported that INI1 is inhibitory to early events [38]. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27766426 Another study did not find inhibitory effect, but found that INI1 was not required, by using siRNA analysis [27]. Interestingly, these two reports differ in their conclusions about the role of INI1 in late events. The first study report that INI1 knock-down in the producer cells has no effect on subsequent infectivity of the virions [38]. On the other hand, the second study reported that there was inhibition of p24 production in P4 cells in which INI1 was knocked down using siRNA, indicating that INI1 may be required for late events [27]. Thus, the role of INI1 in late events in the producer cells or the role of virion-associated INI1 in early events remains unresolved. INI1 has been demonstrated to be a tumor suppressor biallelically altered in rhabdoid tumors, an aggressive pediatric malignancy [39]. These alterations include either large changes involving the deletions spanning INI1/ hSNF5, and/or subtle modifications involving point mutations and substitutions in this gene [40-42]. The cell lines derived from these rhabdoid tumors are INI1-defective, and hence are excellent reagents to study the effect of lack of INI1 on HIV-1 replication. Previously we have reported that HIV-1 particle production is reduced in MON cells, one of the rhabdoid cell lines carrying biallelic deletions of INI1 gene. Reduction in the particle production could be complemented by co-expression of INI1 in MON cells along with viral proteins [22]. However it was not clear if the inhibition of particle production is specific to MON cells or is observed in other rhabdoid cell lines.Page 2 of(page number not for citation purposes)Retrovirology 2006, 3:http://www.retrovirology.com/content/3/1/Furthermore, the stage at which the d.