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dc.contributor.authorVenkatachari, NJ
dc.contributor.authorZerbato, JM
dc.contributor.authorJain, S
dc.contributor.authorMancini, AE
dc.contributor.authorChattopadhyay, A
dc.contributor.authorSluis-Cremer, N
dc.contributor.authorBar-Joseph, Z
dc.contributor.authorAyyavoo, V
dc.date.accessioned2020-12-22T03:04:02Z
dc.date.available2020-12-22T03:04:02Z
dc.date.issued2015-10-06
dc.identifierpii: 10.1186/s12977-015-0211-3
dc.identifier.citationVenkatachari, N. J., Zerbato, J. M., Jain, S., Mancini, A. E., Chattopadhyay, A., Sluis-Cremer, N., Bar-Joseph, Z. & Ayyavoo, V. (2015). Temporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch.. Retrovirology, 12 (1), pp.85-. https://doi.org/10.1186/s12977-015-0211-3.
dc.identifier.issn1742-4690
dc.identifier.urihttp://hdl.handle.net/11343/257771
dc.description.abstractBACKGROUND: Latent HIV-1 reservoirs are identified as one of the major challenges to achieve HIV-1 cure. Currently available strategies are associated with wide variability in outcomes both in patients and CD4(+) T cell models. This underlines the critical need to develop innovative strategies to predict and recognize ways that could result in better reactivation and eventual elimination of latent HIV-1 reservoirs. RESULTS AND DISCUSSION: In this study, we combined genome wide transcriptome datasets post activation with Systems Biology approach (Signaling and Dynamic Regulatory Events Miner, SDREM analyses) to reconstruct a dynamic signaling and regulatory network involved in reactivation mediated by specific activators using a latent cell line. This approach identified several critical regulators for each treatment, which were confirmed in follow-up validation studies using small molecule inhibitors. Results indicate that signaling pathways involving JNK and related factors as predicted by SDREM are essential for virus reactivation by suberoylanilide hydroxamic acid. ERK1/2 and NF-κB pathways have the foremost role in reactivation with prostratin and TNF-α, respectively. JAK-STAT pathway has a central role in HIV-1 transcription. Additional evaluation, using other latent J-Lat cell clones and primary T cell model, also confirmed that many of the cellular factors associated with latency reversing agents are similar, though minor differences are identified. JAK-STAT and NF-κB related pathways are critical for reversal of HIV-1 latency in primary resting T cells. CONCLUSION: These results validate our combinatorial approach to predict the regulatory cellular factors and pathways responsible for HIV-1 reactivation in latent HIV-1 harboring cell line models. JAK-STAT have a role in reversal of latency in all the HIV-1 latency models tested, including primary CD4(+) T cells, with additional cellular pathways such as NF-κB, JNK and ERK 1/2 that may have complementary role in reversal of HIV-1 latency.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTemporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch.
dc.typeJournal Article
dc.identifier.doi10.1186/s12977-015-0211-3
melbourne.affiliation.departmentDoherty Institute
melbourne.source.titleRetrovirology
melbourne.source.volume12
melbourne.source.issue1
melbourne.source.pages85-
dc.rights.licenseCC BY
melbourne.elementsid1125887
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594640
melbourne.contributor.authorZerbato, Jennifer
dc.identifier.eissn1742-4690
melbourne.accessrightsOpen Access


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