Matches in SemOpenAlex for { <https://semopenalex.org/work/W2893238984> ?p ?o ?g. }
- W2893238984 abstract "Abstract A major barrier to curing HIV is the long-lived latent reservoir that supports re-emergence of HIV upon treatment interruption. Targeting this reservoir will require mechanistic insights into the establishment and maintenance of HIV latency. Whether T cell signaling at the time of HIV-1 infection influences productive replication or latency is not fully understood. We used a panel of chimeric antigen receptors (CARs) with different ligand binding affinities to induce a range of signaling strengths to model differential T cell receptor signaling at the time of HIV-1 infection. Stimulation of T cell lines or primary CD4+ T cells expressing chimeric antigen receptors supported HIV-1 infection regardless of affinity for ligand; however, only signaling by the highest affinity receptor facilitated HIV-1 expression. Activation of chimeric antigen receptors that had intermediate and low binding affinities did not support provirus transcription, suggesting that a minimal signal is required for optimal HIV-1 expression. In addition, strong signaling at the time of infection produced a latent population that was readily inducible, whereas latent cells generated in response to weaker signals were not easily reversed. Chromatin immunoprecipitation showed HIV-1 transcription was limited by transcriptional elongation and that robust signaling decreased the presence of negative elongation factor, a pausing factor, by more than 80%. These studies demonstrate that T cell signaling influences HIV-1 infection and the establishment of different subsets of latently infected cells, which may have implications for targeting the HIV reservoir. Author Summary Activation of CD4+ T cells facilitates HIV-1 infection; however, whether there are minimal signals required for the establishment of infection, replication, and latency has not been explored. To determine how T cell signaling influences HIV-1 infection and the generation of latently infected cells, we used chimeric antigen receptors to create a tunable model. Stronger signals result in robust HIV-1 expression and an inducible latent population. Minimal signals predispose cells towards latent infections that are refractory to reversal. We discovered that repression of HIV-1 transcription immediately after infection is due to RNA polymerase II pausing and inefficient transcription elongation. These studies demonstrate that signaling events influence the course of HIV-1 infection and have implications for cure strategies. They also provide a mechanistic explanation for why a significant portion of the HIV latent reservoir is not responsive to latency reversing agents which function by modifiying chromatin." @default.
- W2893238984 created "2018-10-05" @default.
- W2893238984 creator A5009732788 @default.
- W2893238984 creator A5015981980 @default.
- W2893238984 creator A5024819794 @default.
- W2893238984 creator A5038720311 @default.
- W2893238984 creator A5046546011 @default.
- W2893238984 creator A5058734327 @default.
- W2893238984 date "2018-10-01" @default.
- W2893238984 modified "2023-09-23" @default.
- W2893238984 title "Strength of T cell signaling regulates HIV-1 replication and establishment of latency" @default.
- W2893238984 cites W1889176404 @default.
- W2893238984 cites W1966066354 @default.
- W2893238984 cites W1980668957 @default.
- W2893238984 cites W1980861325 @default.
- W2893238984 cites W2000862651 @default.
- W2893238984 cites W2001074195 @default.
- W2893238984 cites W2004223360 @default.
- W2893238984 cites W2004937435 @default.
- W2893238984 cites W2016103121 @default.
- W2893238984 cites W2025382683 @default.
- W2893238984 cites W2025481552 @default.
- W2893238984 cites W2049653440 @default.
- W2893238984 cites W2055796578 @default.
- W2893238984 cites W2057516022 @default.
- W2893238984 cites W2058486365 @default.
- W2893238984 cites W2059944494 @default.
- W2893238984 cites W2060829964 @default.
- W2893238984 cites W2060993125 @default.
- W2893238984 cites W2061921043 @default.
- W2893238984 cites W2068173904 @default.
- W2893238984 cites W2081540048 @default.
- W2893238984 cites W2081550246 @default.
- W2893238984 cites W2090646713 @default.
- W2893238984 cites W2091218020 @default.
- W2893238984 cites W2092284137 @default.
- W2893238984 cites W2094434723 @default.
- W2893238984 cites W2109010689 @default.
- W2893238984 cites W2115580899 @default.
- W2893238984 cites W2131042657 @default.
- W2893238984 cites W2131466396 @default.
- W2893238984 cites W2139833144 @default.
- W2893238984 cites W2150645172 @default.
- W2893238984 cites W2151750297 @default.
- W2893238984 cites W2156075763 @default.
- W2893238984 cites W2159367056 @default.
- W2893238984 cites W2160706185 @default.
- W2893238984 cites W2167778463 @default.
- W2893238984 cites W2171770874 @default.
- W2893238984 cites W2225775312 @default.
- W2893238984 cites W2270979736 @default.
- W2893238984 cites W2322237813 @default.
- W2893238984 cites W2335585363 @default.
- W2893238984 cites W2465973416 @default.
- W2893238984 cites W2563681779 @default.
- W2893238984 cites W2567822565 @default.
- W2893238984 cites W2809359420 @default.
- W2893238984 cites W2883260559 @default.
- W2893238984 cites W2888147286 @default.
- W2893238984 doi "https://doi.org/10.1101/432401" @default.
- W2893238984 hasPublicationYear "2018" @default.
- W2893238984 type Work @default.
- W2893238984 sameAs 2893238984 @default.
- W2893238984 citedByCount "0" @default.
- W2893238984 crossrefType "posted-content" @default.
- W2893238984 hasAuthorship W2893238984A5009732788 @default.
- W2893238984 hasAuthorship W2893238984A5015981980 @default.
- W2893238984 hasAuthorship W2893238984A5024819794 @default.
- W2893238984 hasAuthorship W2893238984A5038720311 @default.
- W2893238984 hasAuthorship W2893238984A5046546011 @default.
- W2893238984 hasAuthorship W2893238984A5058734327 @default.
- W2893238984 hasBestOaLocation W28932389841 @default.
- W2893238984 hasConcept C102906071 @default.
- W2893238984 hasConcept C104317684 @default.
- W2893238984 hasConcept C140704245 @default.
- W2893238984 hasConcept C141231307 @default.
- W2893238984 hasConcept C159047783 @default.
- W2893238984 hasConcept C170493617 @default.
- W2893238984 hasConcept C203014093 @default.
- W2893238984 hasConcept C2522874641 @default.
- W2893238984 hasConcept C2776090121 @default.
- W2893238984 hasConcept C2778852064 @default.
- W2893238984 hasConcept C2908647359 @default.
- W2893238984 hasConcept C3875195 @default.
- W2893238984 hasConcept C54355233 @default.
- W2893238984 hasConcept C552990157 @default.
- W2893238984 hasConcept C62478195 @default.
- W2893238984 hasConcept C71924100 @default.
- W2893238984 hasConcept C83640560 @default.
- W2893238984 hasConcept C86339819 @default.
- W2893238984 hasConcept C86803240 @default.
- W2893238984 hasConcept C8891405 @default.
- W2893238984 hasConcept C95444343 @default.
- W2893238984 hasConcept C99454951 @default.
- W2893238984 hasConceptScore W2893238984C102906071 @default.
- W2893238984 hasConceptScore W2893238984C104317684 @default.
- W2893238984 hasConceptScore W2893238984C140704245 @default.
- W2893238984 hasConceptScore W2893238984C141231307 @default.
- W2893238984 hasConceptScore W2893238984C159047783 @default.
- W2893238984 hasConceptScore W2893238984C170493617 @default.