Blog

RF1 Actions 8/21/23

Hello HOPEians,

Here is an update on the RF1 meeting from August 21, 2023. If you have any questions, please reach out to Susana Valente and Doug Nixon.

Actions:

  • Susana Valente – Schedule a meeting with Cedric to go over DUX4 data

  • Roan Lab – Look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)

  • (In progress) Luisa Mori, Ana Leda, and Susana Valente considering writing a review/summary of all the HIV latency models

Updates:

We heard updates from Quentin Gibaut (Valente Lab) on FUBP3 data,  Qifan Wang (Valente Lab) on  p32 data, and Nick Dopkins (Nixon Lab) on transposable element expression.

Quentin Gibaut (Valente Lab) presented on the host factor FUBP3 promotes HIV transcription. Quentin went into the background of identifying FUBP3 as an HIV transcriptional activator. The chaperone protein p32 was recently discovered to interact with Tat and promote HIV transcription. There are 161 proteins identified through ChAP-MS. ChAP-MS is a new technique to identify proteins involved in the HIV machinery. The goal is to identify the enrichment or loss of proteins in transcriptionally active or silenced HIV promoter loci. The advantages of this are it is selective for HIV and has unbiased detection of multiple proteins associated with the DNA target. FUBP3 was identified by ChAP-MS as an HIV activator.

He shared validation data of FUBP3 as an HIV transcription activator and the mechanistic studies of FUBP3 in the HIV transcription machinery. For future studies, the Valente lab will try to find stimulation pathways and run ChipSeq to share a global overview of the infections. They will try to determine which part of the proteins are required for this, run MD stimulation of FUBP3 to Tat, Chip in JLat -10.6, and the effects of FUBP3 overexpression.

Qifan Wang (Valente Lab) shared the activity of prohibitin-2 in HIV-1 transcriptional regulation and reactivation. He shared data on the prohibitin 2 (PHB2) function. PHB2 expression decreases after HIV infection in primary CD4+ T cells and expression is reduced in the HIV GFP population. PHB2 overexpression inhibits HIV production in 293T cells. PHB2 reduces HIV LTR activity and restricts HIV reactivation in Jurkat 10.6 cells. The preliminary data evidence shows PHB2 plays a negative role in primary CD4+T cell infected with HIV. He shared a paper in Nature, Global landscape of HIV-human protein complexes that shows The PHB2 Co-IPs with Tat.

Qifan summarized that PHB2 expression was decreased during HIV transactivation. CHip-PCR showed PHB2 binding to the LTR and its loss during reactivation. PHB2 OE reduces HIV LTR transactivation driven by Tat and PMA. PHB2 restricts HIV reactivation in Jurkat 10.6 cells. PHB2 binds to tat, likely via the basic and core domains. For future studies, they plan to construct a series of PHB2 deletion variants and deliver them into J-Lat cells with the endogenous PHB2 depleted by shRNAs to define PHB2 domains involved in LTR binding. They will perform RNAseq after PHB2 knockdown in HIV-infected primary CD4+ T cells and study if there is an indirect activity of PHB2 on HIV activity. Lastly, they will perform ChIP studies to confirm the epigenetic outcome of each of the factors recruited by PHB2.

Nick Dopkins from the Nixon Lab shared updates on the transposable element (TEs) expression in the gut microenvironment of people living with HIV (PLWH). The TEs comprise a substantial fraction of the human genome. They looked at the activation of human endogenous retroviruses and its physiological consequences. He shared the paper from Plos Pathogens, Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis. The data shows gut biopsies and interferome analysis of gut CD4+ T cells.  TEs are modulated in the gut and influence the HIV status on TE expression in the gut. There is an impact of type 1 interferons on TE expression in gut CD4+ T cells. He shared 6 of his favorite HERV lines that interplay between interferons and HIV status on TE expression in the gut microenvironment.

In summary, they are testing the expression of certain HERV elements, such as LTR19_12p13.31. This is indicative of an overabundant antiviral response observed in the hit microenvironment of PLWH pre-ART. Antigen-presenting mDCs and CD4 populations seem primarily unchanged in the gut. The HERV activity in the gut microenvironment is modulated in PLWH, with TYPE 1 interferons processing shared and differential induction in their expression. The incorporation of HERV activity to interferon-centric studies could explain the heterogeneity of prognostic outcomes in PLWH. In the future, they will work to quantify the expression of differentially expressed TEs in the PBMC data from the same patients and define physiological roles for differentially expressed TEs.

Announcements:

  • The HOPE Collaboratory-Wide Meeting is on Monday, Sept 25th at 9am PT/ 12pm ET

  • The next RF1 standing meeting will be Oct 16th, 2023

  • Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

RF1 Actions 6/28/23

Hello HOPEians, 

Here is an update on the RF1 meeting from June 28, 2024.

We heard updates from Ursula Schulze-Gahmen (Ott Lab) on RNA conformational propensities determine cellular activity and Ifeanyi Ezeonwumelu (Roan Lab) on targeting the CD127-expressing tissue reservoir by ADCC in the tonsil model.

Actions:

  • Susana Valente – Schedule a meeting with Cedric to go over DUX4 data

  • Roan Lab – Look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)

  • (In progress) Luisa Mori, Ana Leda, and Susana Valente considering writing a review/summary of all the HIV latency models

Ursula Schulze-Gahmen 

Ursula presented on “RNA conformational propensities determine cellular activity”. In contrast to previous studies on the role of RNA in cellular processes, this work focuses on a quantitative approach to test if the hierarchical organization holds for the cellular activity of HIV-1 TAR.
In the shared study, they used TAR variants that were designed to probe the effect of conformational energetic penalties on the cellular activity of TAR in HIV transcription.  Conformational penalties include stacking energy to convert the predominantly bent TAR molecules into linear stacked molecules, and the energy to form the triple base between U23 and A27-U23. By modulating the TAR-bulge size and introducing mutations that disrupt the essential base-triple motif, they were able to correlate the resulting energetic penalties with the energetics of transactivation by TAR. The study showed that the relatively rare high-energy conformation of TAR is critical for transactivation and that it is important to go beyond probing the dominant structures in vitro and in vivo to quantitatively measure ensembles that describe the propensities to form a biologically active conformational state.

Ifeanyi Ezeonwumelu

Ifeanyi Ezeonwumelu from the Roan Lab presented on targeting the CD127-expressing tissue reservoir by ADCC in the tonsil model.  Ifeanyi shared the Therapeutic strategy to target the IL-7Rɑ (CD127) by antibody-mediated cell-dependent cytotoxicity.  T cells acute lymphoblastic leukemia (T-ALL) are the most common malignancy in children. He shared finds from the paper “New anti-IL-7Rα monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models”. The antibodies are dependent on cellular cytotoxicity (ADCC) and antibodies bind to antigens on target cells. So can we adapt ADCC to specifically target latent HIV-infected memory cells? Can we target the elimination of cells that are highly susceptible to HIV infection when looking at the gating strategy for characterizing the latently-infected CD127+ cells and target HIV-infected CD127+ cells for AdCC depletion? The anti-hIL-7Rɑ antibody 4A10 facilitated a significant depletion of HIV-1 infected cells ex vivo during 3 independent experiments. The next steps are to include more donors and determine the impact of ADCC depletion on latency reactivation in the HIV-infected HLAC model.

Announcements:

  • Y3 subcontracts are being issued.  All Year 2 invoices were due June 30, 2023

  • The HOPE Collaboratory-Wide Meeting is on Monday, July 10th, 9am PT/ 12pm ET

  • The next RF1 standing meeting will be Aug 21, 2023

  • Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include. 

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

RF1 Actions 4/17/23

Hello HOPEians,

Here is an update on the RF1 meeting from April 17th, 2023.

We heard updates from Ana Leda on dCA-resistant viruses, Zichong Li on activating PP2A and inhibiting P-TEFb synergistically block reactivation of latent HIV, and Smitha Srinivasachar Badarinarayan on TRIM22/ZNF579 as silencers of HIV.

Ana Leda- dCA Resistant Viruses

Ana came back to present on her last project in the Valente Lab focusing on the loss of in vivo replication fitness of HIV-1 variants to the tat-inhibitor – dCA. She shared some data from the paper: Resistance to the Tat Inhibitor Didehydro-Cortistatin A Is Mediated by Heightened Basal HIV-1 Transcription. When testing ultra-deep sequences to identify dCA resistance, they found no mutations in Tat or Tar. In collaboration with Dr. Victor Garcia, they used his humanized mouse models to test for in Vivo replication kinetics of dCA-resistance viruses and t-cells evaluated weekly. The wild-type infected animals are more prone to infections. Ana shared data shared on human T-cell levels in peripheral blood and the frequency of activated human T-cells in peripheral blood. dCA-resistant HIV-1 variants established a systemic infection in humanized mice. The hypothesis was dCA-resistant HIV-1 variants do not elicit INF responses. They submitted plasma samples for a Luminex analysis for different levels of cytokines and found no difference between M1 and M2 animals. The ability of dCA-resistant HIV-1 variants to establish infection correlated with reversion to wild-type. In conclusion, they found that in vitro-selected dCA-resistant variants have high replication fitness and elevated cytopathogenicity in vitro they are not fit in vivo. They also found that dCA-resistant viruses identified in vitro suffer a large fitness cost in vivo, with mutations in the LTR and nef regions the most pressure to revert to wild type.

Zichong Li- “Activating PP2A and inhibiting P-TEFb synergistically block reactivation of latent HIV”

Zichong validated using siRNAs the synergies between INTS2, PSMD8, and FTSJ3 identified by CRISPRi screens. The FTSJ3 had proteasomes synergize with an integrator, but not each other. There is a synergistic effect between the two drugs. AZD4573 + SMAP-2 blocks and locks latent HIV in cell lines and a primary cell model. The epigenetics changed by the combination of AZD4573 + SMAP-2 on HIV LTR include increased H3K9me3 and H3K27me3 in the Nuc-1 region. Looking at the cellular toxicity tests for AZD4573 + SMAP-2 he found that one-day treatment is tolerated, but on day two the cells die. In the future Zichong will test new HIV Silencing promoting agents and look for synergy with other SPAs; side effects; and longer locking effects. Zichong found that AZD4573 + SMAP-2 could block HIV reactivation and induce inhibitory epigenetic changes on HIV LTR that can last for at least six days. Among the epigenetic changes are increased levels of H3K27me3, which plays a major role in silencing latent HIV.

Smitha Srinivasachar Badarinarayan -TRIM22/ZNF579 as silencers of HIV

Smitha gave updates and background on TRIM22. TRIM22 is a member of the family of tripartite motif proteins, and interferons induce it, restrict IAV, HCV, HBV, etc. via different mechanisms and inhibit HIV transcription, and promote HIV latency. Feschotte lab observed that TRIM22 binding colocalizes with CTCF genome-wide and a further decrease in CTCF binding in TRIM22-depleted cells. CTCF is a regulator of HIV latency. It is involved in many cellular processes, including transcription regulation, insulator activity, and regulation of chromatin architecture. There was a significant overlap between TRIM22 and CTCF ChIP-seq peak. They found an overlap of ChIP-seq peaks between ZNF579 and TRIM22 genomic bindingFurther, found a predicted binding motif of ZNF579 was within the HIV-1 LTR. They plan to validate TRIM22 findings; co-immunoprecipitation to determine if TRIM22 can bind directly or indirectly to CTCF or other factors; TRIM22 HiC/4C-seq; analyze the effect the ZNF579 and TRIM22 on HIV-1 latency in JLat A2 GFP cell line model; and RNA and protein expression of TRIM22/ZNF579 in HIV-1 infected samples. Preliminary results showed that TRIM22 reduced reactivated HIV-1 in stimulated Jlat GFP cells.

Actions for next meeting:

  • Susana Valente – Schedule a meeting with Cedric to go over DUX4 data
  • Roan Lab – Look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)
  • (In progress) Luisa Mori, Ana Leda, and Susana Valente considering writing a review/summary of all the HIV latency models

Announcements:

  • Check out the Block, Lock, Excise for HIV Cure animation Here! 
  • The HOPE Collaboratory-Wide Meeting is on Monday, May 22, 9am PT/ 12pm ET
  • The next RF1 standing meeting will be on June 28th
  • Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

Rapamycin Working Group Summary 1/17/23

Hello everyone,

Great working group yesterday! I will work on scheduling a follow-up Rapamycin Working Group Meeting. Here is a summary from today’s, January 17, 2023, meeting:

Eric Verdin from the Buck Institute provided background and updates on rapamycin in aging. mTOR signaling is the target of rapamycin. mTOR signaling in T cells involves metabolic cues, antigen recognition, and immunologic cues. Rapamycin can inactivate the mTORC1 complex more predominantly; however, the mTORC2 complex is inhibited with chronic rapamycin treatment. Rapamycin has been routinely used in the aging field because there is evidence that rapamycin treatment increases life span in mice  (ex: lifespan in mice can increase from 9% to 26% in almost all experiments and sometimes ranges from 30-100% increase).

Testing rapamycin in humans has not been as successful. They found that rapamycin tricks the body into thinking that there is not enough energy coming in and begins the fasting mode (even if you eat, your body thinks you are fasting). This can cause humans to lose weight and muscle. When you have high glucose levels, then insulin secretion and mTORC1 activation is triggered. There is no evidence that rapamycin works in decreasing the aging process in humans and is a drug for immunosuppression. However, there are some positive studies with primates, mice, and dogs. There is growing evidence that inactivating mTORC2 leads to side effects, whereas mTORC1 targeting may be desirable. Humans that are taking it once a week have more inhibition of mTORC1 and not mTORC2 (no side effects with 1x/week). The half-life of the drug is 36 hrs. How does it affect the lifespan of cells? In vitro replicative lifespan is generally used as a test for viability. This has not been tested in the Verdin lab, but Eric guessed that if you add rapamycin it might stop the replication of the cells. Telomere length can also be preserved.

Papers that were discussed:

Rapamycin Reduces CCR5 Density Levels on CD4 T Cells, and This Effect Results in Potentiation of Enfuvirtide (T-20) against R5 Strains of Human Immunodeficiency Virus Type 1 In Vitro.

FOXO1 promotes HIV latency by suppressing ER stress in T cells.

Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway

Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells

Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.

This last study looks at the suppression of ART after 31 days and then administering rapamycin. Administered anti-CD3 in animals with rapamycin. Tim Henrick commented that monkey studies had really high concentrations of rapamycin (compared to his human studies). This may be because monkeys have higher levels of exposure than humans. The tissue and plasma concentrations in NHPs were way above that in humans treated long-term.

Avi Nath discusses his study: Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway. They showed the mTOR pathway is activated by interactions between the envelope protein of HERV-K and CD98 heavy chain. They also showed a novel interaction between mTOR and LPCAT-1 which regulates histone 4 deacetylation. In the context of human endogenous retroviruses (HERVs), there is a small number of transcription factors. HML-2 LTR can regulate the expression of host genes as promoters and enhancers. He shared some data from the paper: Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. They are interested in brain studies. If you over-express in stem cells, they will produce tumors, and the expression of neurons leads to motor neuron disease. The study shares the different effects of HML-2 expression.

RF1 Actions 12/19/22

Hello HOPEians,

Happy Holidays!

During the RF1 meeting on Dec 19, 2022, we discussed some weaknesses from the SAB report and heard a lecture from Helena Reyes-Gopar (Nixon Lab) at the Instituto Nacional De Medicina Genómica about “Stellarscope quantifies the expression of transposable elements at locus resolution in single cells.” To summarize, Helena shared that they created a tool to set in motion single-cell retrotranscriptomics; they are characterizing HERV transcription in single PBMCs, and stellarscope uses a scRNA-seq alignment and your annotation to provide a matrix that includes counts for your elements (e.g HERVs).

Down the line, the Nixon Lab plans to look at more than one donor, sort T cells and monocytes, and create a small list of TEs that are expressed. Michael Corley suggested looking at methylation/chromatin data from sorted cells to orthogonally validate and also distinguish self-expressed TEs from those co-transcribed with host genes. Ulrike mentioned that they are working with bulk and mapping to HERV by taking different public datasets and found CD4 signatures. ATAC data is generally less recalcitrant to mapping because they often overlap TE and uniquely mapping flanking sequences.

One of the weaknesses that was discussed was:

“The aims of RF1 were not all totally compelling. Testing for synergy of repressive factors might be helpful but probably not groundbreaking. Looking to HERVs as models for chromatin based repression may or may not pay off – they are mostly repressed by DNA methylation in mature cells, which allows for shutoff of embryonic ZNF genes. Perhaps this is suggesting a focus on DNA methylation, though. Not sure studying tat-independent virus will be helpful.”

In the next SAB meeting, we could do better explaining the big points in the presentations and describing the physiology in more detail. We could try to understand how different HERVs located in different loci are expressed differently and look for targeted M-seq and HERV classes.

In an upcoming Scientific Working Group – HERV & HIV on January 23rd from 10-11 am PT, Cedric, Ulrike, and Zichong are working on screening zinc finger proteins for silencers and Zichong already received some good results that will be discussed further in the next meeting.

Actions for the next meeting:

  • Susana Valente – Schedule meeting with Cedric to go over PITCH approach for HERVs

  • Roan Lab – Look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)

  • (In progress) Luisa Mori, Ana Leda, and Susana Valente considering writing a review/summary of all the HIV latency models

Announcements:

  • The HOPE Collaboratory-Wide Meeting is on Tuesday, January 17, 2023, 12-1 pm PT

  • There is a Scientific Working Group – HERV & HIV on January 23rd from 10-11 am PT

  • The next RF1 standing meeting will be in February: Date TBD and we will discuss new HERV projects

  • Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

RF1 Actions 10/17/22

Hello HOPEians,

During the RF1 meeting on October 17th, 2022 we discussed the new RF/Collaboratory wide format and who would submit abstracts for the HIV Persistence meeting in Miami. Attached are the Management & Operations Updates.

HIV Persistence – International Workshop Miami

Abstracts are due TODAY (by 3pm PT/ 6pm ET)

Please send me your abstracts, so we can decide who will present during the flask talks. Here is a list of individuals that are submitting abstracts (please contact me if I missed someone):

  • Julie Frouard, Zichong Li, Ulrike Lange, Ursula Schulze-Gahmen, Daniela Boehm, Luisa Mori, Sonia Mediouni Jablonski, Michael Corley (2x), Alina Pang, Chuan Li, Priti Kumar

A reminder that the abstracts that you submit will likely get published if chosen. You can have max 10 authors. CROI has some rules about presenting abstracts that have already been presented:

“If study data are accepted for publication or presentation after the abstract submission to CROI, and that publication or presentation is expected to take place before CROI, the presenting author must contact the conference manager at CROIabstracts@iasusa.org to provide details as soon as the presentation is accepted for review, presentation, or publication in another venue or outlet. Please be aware that, while publication in these circumstances will not necessarily prevent presentation of the research at CROI, our strong preference is that any additional publication or presentation happens either simultaneous to or following presentation at CROI. Requests to publish or present research accepted for presentation at CROI prior to its presentation at CROI will be evaluated on a case-by-case basis. Failure to notify the conference promptly regarding plans to publish or present a CROI-accepted abstract prior to CROI may result in the removal of the study from the conference program.”

Here is some language you can use to Acknowledge HOPE & the NIH:

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

New RF Structure

The RF meeting structure will change beginning in November.  For the rest of October, each RF will hold its monthly meeting.  In November, a larger group meeting will take place in lieu of the individual RF meetings.  These will alternate every month.

RF1 Actions 7/18/22

Hello HOPEians,

Here is a quick update on the RF1 meeting from July 18th, 2022.

During the RF1 meeting, Cedric Feschotte (Cornell University) shared updates that Sabrina Leddy has started working in his lab on HERV expression in HIV elite controllers and Julius Judd who was previously working on zinc fingers is leaving his lab soon. Susana Valente (University of Florida) explained her research with DUX4, FUBP3, dCA-resistant viruses, and how p32 interacts with Tat’s basic domain.

Zichong Li (Greene Lab at Gladstone) discussed different epigenetic modifiers and the effects of new SPAs and the nucleosomal modification mechanisms for silencing HIV.  Martin Kinisu (Greene Lab) also shared his work on CRISPRoffV2 combining DNA and H3K9 methylation, the optimization of KRAB domain for HIV silencing, and exploring inducible expression systems using the piggyback technology. In his early findings, Martin found that ETRs transiently silence HIV reactivation in 30-70% of cells. Melanie Ott and Daniela Boehm (Gladstone) resubmitted their SYMD5 paper and performed the SMYD5 rescue experiment in 5A8 J-Lat cells. Their findings show that SYMD5 is highly expressed in CD4+ T cells and is a positive regulator of HIV transcription.  SYMD5 also methylates histones and Tat in vitro.

Actions for next meeting:

  • Susana Valente – Schedule a meeting with Cedric to go over DUX4 data

  • Chuan Li – Give MNase-Seq protocol to Zichong Li

  • Roan Lab – Look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)

  • (In progress) Luisa Mori, Ana Leda, and Susana Valente considering writing a review/summary of all the HIV latency models

Announcements:

  • August 15th HOPE – PAVE Guest Speaker: Dr. Persaud

  • The next standing meeting is on Sept 19 – Bharath Sreekumar will give a refresher on their data on transducing T cells.  Cedric Feschotte and Sabrina Leddy will give updates on HERV expression in HIV-1 elite controllers.

  • Call for nominations for the HOPE 2022 Awards (Instructions attached)

  • Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.

“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”

RF1 Actions 5/16/22

Hello HOPEians,

Here is a quick update on the RF1 meeting from 5/16.  

During the RF1 meeting, Sonia Jablonski, a Staff Scientist in the Valente lab discussed transcriptional crosstalk between DUX4-FL and HIV-1. Martin Kinisu from the Greene lab discussed recent work on vetting CRISPR-off (7kb) as a latency promoting factor and testing variable KRAB domains. Zichong Li from the Greene lab discussed three factors that can play a role in the efforts to block & lock HIV outside of the 30 synergies identified among 10 silencing factors. Bharath Sreekumar from the Ott Lab gave an update on transducing t-cells. Thomas Premeaux shared information from the Johnathan Karn paper on The Glucocorticoid Receptor Is a Critical Regulator of HIV Latency in Human Microglial Cells. Melanie led a discussion of new ETRs including BRECiB.

 Actions for next meeting:

  • Cedric – Share data on ZNF579 with Susana
  • Roan lab – look for DUX4 expression in single-cell RNAseq tonsil datasets (+/- HIV)

Long-Term Actions:

  • Luisa Mori, Ana Leda, and Susana considering writing a review/summary of all the HIV latency models 
  • (T-TRACE) Discuss whether it would make sense to apply T-TRACE when we test block-and-lock agents in humanized mice 
  • (Systems to test spironolactone in, and which concentrations) Roan lab to collect samples to look at XPB and send to Valente Lab
  • (Aim 2) Keep the discussion open on the use of PICh or other methods

At the next meeting on June 29th, we will have a guest speaker, Dr. Mathias Lichterfeld.

RF1 Actions 4/18/22

Hello HOPEians,

Here is a quick update on the RF1 meeting from 4/18.  

In today’s meeting, we discussed HIV and HERVs integration sites, with an overview from Doug, Ulrike, Matthew, and Manu. The slides will be in the RF1 Dropbox later. 

Actions for next meeting:

  • Sydney/Doug – Schedule HIV and HERVs Integration site subgroup meeting
  • Melanie – Follow up if any members of the AIDS malignancy consortium at UCSF/Gladstone. Attempt to identify HIV infected subjects on 2-deoxy-glucose treatment
  • Cedric – Share data on ZNF579 with Susana
  • Susana – Share list of ChAP-MS interactors with Cedric

Long-Term Actions:

  • Luisa Mori, Ana Leda, and Susana considering writing a review/summary of all the HIV latency models 
  • (T-TRACE) Discuss whether it would make sense to apply T-TRACE when we test block-and-lock agents in humanized mice 
  • (Systems to test spironolactone in, and which concentrations) Roan lab to collect samples to look at XPB and send to Valente Lab
  • (Aim 2) Keep the discussion open on the use of PICh or other methods

The next meeting is May 16th and RF1 leaders will follow up with a topic and agenda.

RF1 Actions 3/21/22

Hello HOPEians,

Here is a quick update on the RF1 meeting from 3/21.  

In today’s meeting we got updates from:

  • Feschotte Lab: Julius presented data on ZNF579. ZNF579 interacts with TRIM22 and the PDH complex, potentially interesting for regulation of HIV latency.
  • Greene Lab: Zichong showed preliminary data that overexpressing BCL7C, KANSL2, and SIRT2 enhance HIV latency. 
  • Valente Lab: Updates on p32 regulating HIV transcription. 
  • Ott Lab: Bharath is continuing to collaborate with Ulrike to generate a telomerase immortalized primary T cell with HIV integrated into the BACH2 locus. Daniela is finalizing SMYD5 paper as well as continuing to work with the Toronto group to develop SMYD5 inhibitors (RF2).

Announcements:

  • The next meeting is April 18th – Discuss integration sites of HIV and HERVs and more lab updates

Actions for next meeting:

  • Melanie – Follow up if any members of the AIDS malignancy consortium at UCSF/Gladstone. Attempt to identify HIV infected subjects on 2-deoxy-glucose treatment
  • Cedric – Share data on ZNF579 with Susana
  • Susana – Share list of ChAP-MS interactors with Cedric
  • Subgroup meeting on ZNF579
    • Attendees: Cedric, Julius, Eric, Melanie, Susana, Warner
    • Discuss potential involvement on metabolism and interaction with components of PDH complex
  • Melanie and Susana meet to discuss potentially generating a crystal structure of p32 and Tat (Susana, Melanie, Ursula, Chuan)

Long-Term Actions:

  • Luisa Mori, Ana Leda, and Susana considering writing a review/summary of all the HIV latency models 
  • (T-TRACE) Discuss whether it would make sense to apply T-TRACE when we test block-and-lock agents in humanized mice 
  • (Systems to test spironolactone in, and which concentrations) Roan lab to collect samples to look at XPB and send to Valente Lab
  • (Aim 2) Keep the discussion open on the use of PICh or other methods