29 results on '"Leyre, Louise"'
Search Results
2. Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
- Author
-
Cheong, Jin-Gyu, Ravishankar, Arjun, Sharma, Siddhartha, Parkhurst, Christopher N., Grassmann, Simon A., Wingert, Claire K., Laurent, Paoline, Ma, Sai, Paddock, Lucinda, Miranda, Isabella C., Karakaslar, Emin Onur, Nehar-Belaid, Djamel, Thibodeau, Asa, Bale, Michael J., Kartha, Vinay K., Yee, Jim K., Mays, Minh Y., Jiang, Chenyang, Daman, Andrew W., Martinez de Paz, Alexia, Ahimovic, Dughan, Ramos, Victor, Lercher, Alexander, Nielsen, Erik, Alvarez-Mulett, Sergio, Zheng, Ling, Earl, Andrew, Yallowitz, Alisha, Robbins, Lexi, LaFond, Elyse, Weidman, Karissa L., Racine-Brzostek, Sabrina, Yang, He S., Price, David R., Leyre, Louise, Rendeiro, André F., Ravichandran, Hiranmayi, Kim, Junbum, Borczuk, Alain C., Rice, Charles M., Jones, R. Brad, Schenck, Edward J., Kaner, Robert J., Chadburn, Amy, Zhao, Zhen, Pascual, Virginia, Elemento, Olivier, Schwartz, Robert E., Buenrostro, Jason D., Niec, Rachel E., Barrat, Franck J., Lief, Lindsay, Sun, Joseph C., Ucar, Duygu, and Josefowicz, Steven Z.
- Published
- 2023
- Full Text
- View/download PDF
3. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity
- Author
-
Uzzan, Mathieu, Martin, Jerome C., Mesin, Luka, Livanos, Alexandra E., Castro-Dopico, Tomas, Huang, Ruiqi, Petralia, Francesca, Magri, Giuliana, Kumar, Shashi, Zhao, Qing, Rosenstein, Adam K., Tokuyama, Minami, Sharma, Keshav, Ungaro, Ryan, Kosoy, Roman, Jha, Divya, Fischer, Jeremy, Singh, Harpriya, Keir, Mary E., Ramamoorthi, Nandhini, Gorman, William E. O’, Cohen, Benjamin L., Rahman, Adeeb, Cossarini, Francesca, Seki, Akihiro, Leyre, Louise, Vaquero, Sonia Tejedor, Gurunathan, Sakteesh, Grasset, Emilie K., Losic, Bojan, Dubinsky, Marla, Greenstein, Alexander J., Gottlieb, Zoe, Legnani, Peter, George, James, Irizar, Haritz, Stojmirovic, Aleksandar, Brodmerkel, Carrie, Kasarkis, Andrew, Sands, Bruce E., Furtado, Glaucia, Lira, Sergio A., Tuong, Zewen K., Ko, Huaibin M., Cerutti, Andrea, Elson, Charles O., Clatworthy, Menna R., Merad, Miriam, Suárez-Fariñas, Mayte, Argmann, Carmen, Hackney, Jason A., Victora, Gabriel D., Randolph, Gwendalyn J., Kenigsberg, Ephraim, Colombel, Jean Frederic, and Mehandru, Saurabh
- Published
- 2022
- Full Text
- View/download PDF
4. SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells
- Author
-
Stevenson, Eva M., Terry, Sandra, Copertino, Dennis, Leyre, Louise, Danesh, Ali, Weiler, Jared, Ward, Adam R., Khadka, Pragya, McNeil, Evan, Bernard, Kevin, Miller, Itzayana G., Ellsworth, Grant B., Johnston, Carrie D., Finkelsztein, Eli J., Zumbo, Paul, Betel, Doron, Dündar, Friederike, Duncan, Maggie C., Lapointe, Hope R., Speckmaier, Sarah, Moran-Garcia, Nadia, Papa, Michelle Premazzi, Nicholes, Samuel, Stover, Carissa J., Lynch, Rebecca M., Caskey, Marina, Gaebler, Christian, Chun, Tae-Wook, Bosque, Alberto, Wilkin, Timothy J., Lee, Guinevere Q., Brumme, Zabrina L., and Jones, R. Brad
- Published
- 2022
- Full Text
- View/download PDF
5. The V2 loop of HIV gp120 delivers costimulatory signals to CD4⁺ T cells through Integrin α₄β₇ and promotes cellular activation and infection
- Author
-
Goes, Livia R., Sajani, Alia, Sivro, Aida, Olowojesiku, Ronke, Ray, Jocelyn C., Perrone, Ian, Yolitz, Jason, Girard, Alexandre, Leyre, Louise, Wibmer, Constantinos Kurt, Morris, Lynn, Gorini, Giacomo, Franchini, Genoveffa, Mason, Rosemarie D., Roederer, Mario, Mehandru, Saurabh, Soares, Marcelo A., Cicala, Claudia, Fauci, Anthony S., and Arthos, James
- Published
- 2020
6. Hide and seek: for HIV-infected [CD4.sup.+] T cells, playing well comes with maturity
- Author
-
Leyre, Louise and Jones, R. Brad
- Subjects
Health care industry - Abstract
Antiretroviral therapy suppresses HIV replication but leaves a population of infected [CD4.sup.+] T cells with integrated proviruses. While most of these proviruses contain defects, such as deletions, some intact proviruses persist and can reinitiate viral replication. In this issue of the JCI, Duette, Hiener, and colleagues performed a tour de force proviral landscape analysis on clinical samples collected over many years with in vitro functional assays. The researchers showed that effector memory [CD4.sup.+] T cells provide partial sanctuary to intact proviruses from [CD8.sup.+] T cells and this was associated with superior Nef-mediated MHC-I downregulation relative to less mature [CD4.sup.+] T cell populations. This finding implicates differential immunoevasion as a cell-intrinsic property, influencing proviral persistence, and highlights Nef as a therapeutic target., Collecting needles from 96 haystacks The vast majority (92%-98%) of the HIV-infected cells that persist with antiretroviral therapy (ART) contain proviruses with deletions, premature stop codons, or other defects that [...]
- Published
- 2022
- Full Text
- View/download PDF
7. Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments
- Author
-
RV254/SEARCH010 Study Group, Crowell, Trevor A., Colby, Donn J., Pinyakorn, Suteeraporn, Fletcher, James L. K., Kroon, Eugène, Schuetz, Alexandra, Krebs, Shelly J., Slike, Bonnie M., Leyre, Louise, Chomont, Nicolas, Jagodzinski, Linda L., Sereti, Irini, Utay, Netanya S., Dewar, Robin, Rerknimitr, Rungsun, Chomchey, Nitiya, Trichavaroj, Rapee, Valcour, Victor G., Spudich, Serena, Michael, Nelson L., Robb, Merlin L., Phanuphak, Nittaya, and Ananworanich, Jintanat
- Published
- 2018
8. Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals: Potential Role in Persistent Inflammation and Transcription From Stable HIV-1 Reservoirs
- Author
-
Zaidan, Sarah M., Leyre, Louise, Bunet, Rémi, Larouche-Anctil, Etienne, Turcotte, Isabelle, Sylla, Mohamed, Chamberland, Annie, Chartrand-Lefebvre, Carl, Ancuta, Petronela, Routy, Jean-Pierre, Baril, Jean-Guy, Trottier, Benoit, MacPherson, Paul, Trottier, Sylvie, Harris, Marianne, Walmsley, Sharon, Conway, Brian, Wong, Alexander, Thomas, Réjean, Kaplan, Robert C., Landay, Alan L., Durand, Madeleine, Chomont, Nicolas, Tremblay, Cécile L., and El-Far, Mohamed
- Published
- 2019
- Full Text
- View/download PDF
9. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection
- Author
-
Colby, Donn J., Trautmann, Lydie, Pinyakorn, Suteeraporn, Leyre, Louise, Pagliuzza, Amélie, Kroon, Eugène, and Rolland, Morgane
- Subjects
Genotypes -- Research ,HIV infections -- Genetic aspects -- Drug therapy -- Research ,Antiretroviral agents -- Dosage and administration ,Medical schools ,HIV ,Highly active antiretroviral therapy ,RNA ,Biological sciences ,Health - Abstract
Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV. Initiation of antiretroviral therapy in the first 2 weeks of HIV infection fails to prevent resurgence of virus after stopping treatment, indicating early establishment of a resilient viral reservoir., Author(s): Donn J. Colby [sup.1] , Lydie Trautmann [sup.2] [sup.3] , Suteeraporn Pinyakorn [sup.2] [sup.3] , Louise Leyre [sup.4] , Amélie Pagliuzza [sup.4] , Eugène Kroon [sup.1] , Morgane Rolland [...]
- Published
- 2018
- Full Text
- View/download PDF
10. SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells
- Author
-
Jones, R. Brad, primary, Stevenson, Eva, additional, Terry, Sandra, additional, Copertino, Dennis, additional, Leyre, Louise, additional, Ward, Adam, additional, Khadka, Pragya, additional, Ellsworth, Grant, additional, Johnston, Carrie, additional, Papa, Michelle Premazzi, additional, Nicholes, Samuel, additional, Caskey, Marina, additional, Gaebler, Christian, additional, Wilkin, Timothy, additional, Lynch, Rebecca, additional, Lee, Guinevere, additional, Weiler, Jared, additional, Zumbo, Paul, additional, Betel, Doron, additional, Dündar, Friederike, additional, Duncan, Maggie, additional, Lapointe, Hope, additional, Speckmaier, Sarah, additional, Moran-Garcia, Nadia, additional, Chun, Tae-Wook, additional, Brumme, Zabrina, additional, Danesh, Ali, additional, Bernard, Kevin, additional, Stover, Carissa, additional, and McNeil, Evan, additional
- Published
- 2022
- Full Text
- View/download PDF
11. Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors
- Author
-
Cheong, Jin-Gyu, primary, Ravishankar, Arjun, additional, Sharma, Siddhartha, additional, Parkhurst, Christopher N., additional, Nehar-Belaid, Djamel, additional, Ma, Sai, additional, Paddock, Lucinda, additional, Fatou, Benoit, additional, Karakaslar, Onur, additional, Thibodeau, Asa, additional, Bale, Michael J., additional, Kartha, Vinay K., additional, Yee, Jim K, additional, Mays, Minh Yen, additional, Leyre, Louise, additional, de Paz, Alexia Martinez, additional, Daman, Andrew W., additional, Mullett, Sergio Alvarez, additional, Robbins, Lexi, additional, LaFond, Elyse, additional, Weidman, Karissa, additional, Racine-Brzostek, Sabrina, additional, Yang, He S., additional, Price, David, additional, Jones, Brad, additional, Schenck, Edward J., additional, Kaner, Robert J., additional, Chadburn, Amy, additional, Zhao, Zhen, additional, Steen, Hanno, additional, Pascual, Virginia, additional, Buenrostro, Jason, additional, Niec, Rachel E., additional, Lief, Lindsay, additional, Ucar, Duygu, additional, and Josefowicz, Steven Z., additional
- Published
- 2022
- Full Text
- View/download PDF
12. Selective BCL-X L Antagonists Eliminate Infected Cells from a Primary-Cell Model of HIV Latency but Not from Ex Vivo Reservoirs
- Author
-
Ren, Yanqin, primary, Huang, Szu Han, additional, Macedo, Amanda B., additional, Ward, Adam R., additional, Alberto, Winiffer D. Conce, additional, Klevorn, Thais, additional, Leyre, Louise, additional, Copertino, Dennis C., additional, Mota, Talia M., additional, Chan, Dora, additional, Truong, Ronald, additional, Rohwetter, Thomas, additional, Zumbo, Paul, additional, Dündar, Friederike, additional, Betel, Doron, additional, Kovacs, Colin, additional, Benko, Erika, additional, Bosque, Alberto, additional, and Jones, R. Brad, additional
- Published
- 2021
- Full Text
- View/download PDF
13. SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells.
- Author
-
Stevenson, Eva M., Terry, Sandra, Copertino, Dennis, Leyre, Louise, Danesh, Ali, Weiler, Jared, Ward, Adam R., Khadka, Pragya, McNeil, Evan, Bernard, Kevin, Miller, Itzayana G., Ellsworth, Grant B., Johnston, Carrie D., Finkelsztein, Eli J., Zumbo, Paul, Betel, Doron, Dündar, Friederike, Duncan, Maggie C., Lapointe, Hope R., and Speckmaier, Sarah
- Subjects
SARS-CoV-2 ,HIV ,COVID-19 vaccines ,CYTOTOXIC T cells ,MESSENGER RNA ,T cells ,VACCINATION - Abstract
Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8
+ cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8+ T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR – TNF – NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector function (granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8+ T-cell induction correlated with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. Thus, we report the observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity. Here, the authors show in a cohort of people with HIV, COVID mRNA vaccination is followed by a transient boost in a particular profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA – suggesting productive immune engagement with infected cells. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
14. The V2 loop of HIV gp120 delivers costimulatory signals to CD4+T cells through Integrin α4β7and promotes cellular activation and infection
- Author
-
Goes, Livia R., primary, Sajani, Alia, additional, Sivro, Aida, additional, Olowojesiku, Ronke, additional, Ray, Jocelyn C., additional, Perrone, Ian, additional, Yolitz, Jason, additional, Girard, Alexandre, additional, Leyre, Louise, additional, Wibmer, Constantinos Kurt, additional, Morris, Lynn, additional, Gorini, Giacomo, additional, Franchini, Genoveffa, additional, Mason, Rosemarie D., additional, Roederer, Mario, additional, Mehandru, Saurabh, additional, Soares, Marcelo A., additional, Cicala, Claudia, additional, Fauci, Anthony S., additional, and Arthos, James, additional
- Published
- 2020
- Full Text
- View/download PDF
15. Selective BCL-XL Antagonists Eliminate Infected Cells from a Primary Cell Model of HIV Latency but not from Ex Vivo Reservoirs
- Author
-
Ren, Yanqin, primary, Huang, Szu Han, additional, Macedo, Amanda B., additional, Ward, Adam R., additional, Alberto, Winiffer D. Conce, additional, Klevorn, Thais, additional, Leyre, Louise, additional, Chan, Dora, additional, Truong, Ronald, additional, Rohwetter, Thomas, additional, Zumbo, Paul, additional, Dündar, Friederike, additional, Betel, Doron, additional, Kovacs, Colin, additional, Benko, Erika, additional, Bosque, Alberto, additional, and Jones, R. Brad, additional
- Published
- 2020
- Full Text
- View/download PDF
16. Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8 + T Cell Function Reveals Multiple Limitations of Class I-Selective Histone Deacetylase Inhibitors during HIV-1 Latency Reversal
- Author
-
Mota, Talia M., primary, McCann, Chase D., additional, Danesh, Ali, additional, Huang, Szu-Han, additional, Magat, Dean B., additional, Ren, Yanqin, additional, Leyre, Louise, additional, Bui, Tracy D., additional, Rohwetter, Thomas M., additional, Kovacs, Colin M., additional, Benko, Erika, additional, MacLaren, Lynsay, additional, Wimpelberg, Avery, additional, Cannon, Christopher M., additional, Hardy, W. David, additional, Safrit, Jeffrey T., additional, and Jones, R. Brad, additional
- Published
- 2020
- Full Text
- View/download PDF
17. Établissement et persistance du réservoir du VIH chez des individus traités très tôt en phase aigüe de l’infection (cohorte RV254)
- Author
-
Leyre, Louise and Roger, Michel
- Subjects
Lymphoid tissues ,Memory CD4+ T cells ,Infection aigüe ,Early treatment ,Tissus lymphoïdes ,Cellules T CD4+ mémoires ,Traitement précoce ,Acute infection ,Réservoir du VIH ,HIV reservoir - Abstract
Les thérapies antirétrovirales (TAR) ont grandement amélioré la qualité de vie des personnes infectées par le VIH qui y ont accès. Cependant, ces thérapies ne permettent pas d’éradiquer le virus qui persiste sous forme latente au sein des cellules T CD4+ de longue vie, formant ainsi un réservoir viral qui représente un des obstacles majeurs vers la guérison du VIH. De nombreuses études ont montré que l’initiation de TAR en phase aigüe permet de retarder le rebond viral voire même dans certains cas de contrôler la virémie du virus suite à une interruption de traitement. Néanmoins, le moment et la localisation de l’établissement du réservoir du VIH pendant l’infection aigüe restent incertains. En utilisant des échantillons de sang et de tissus lymphoïdes de participants en phase aigüe d’infection, nous montrons que le virus s’intègre en premier lieu dans les cellules des ganglions lymphatiques et du colon et atteint des fréquences maximales de cellules infectées dès le stade Fiebig II, soit avant la séroconversion. De plus, nous observons que l’initiation précoce de TAR diminue drastiquement le nombre de cellules infectées et ce dans tous les compartiments. Toutefois quelques cellules infectées persistent dans les ganglions lymphatiques. Nos résultats suggèrent qu’un grand nombre de cellules sont infectées très tôt au cours de l’infection aigüe mais elles forment un réservoir instable qui est rapidement éliminé suite à l’initiation précoce de TAR., Antiretroviral therapies (ART) have largely increased the life expectancy of the HIV infected individuals who have access to it. Nonetheless, these therapies can’t eradicate the virus that persist in a latent state in long-lived CD4+ T cells. These infected cells form a viral reservoir that remains the main obstacle to a cure. Several studies have shown that initiation of ART during the acute infection can lead to a delay in the viral rebound or in some cases to viremia control after a treatment interruption. However, the timing and location of the establishment and persistence of the viral reservoir during acute infection remain unclear. Using, blood and lymphoid tissues samples from acutely infected participants, we observed that the virus is firstly integrated in lymph nodes and colon cells and reaches a maximum frequency of infected cells at the Fiebig stage II, i.e. before seroconversion in the tissues. Moreover, we saw that a very early initiation of ART results in a drastic decrease of the number of infected cells in all compartments. Nonetheless a few infected cells persist under ART in the lymph nodes. Our results suggest that a large number of cells are infected early in tissues before moving into the blood during the acute infection. Nonetheless, these infected cells form a labile HIV reservoir which is rapidly, but incompletely, eliminated by an early initiation of ART.
- Published
- 2019
18. Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus.
- Author
-
Massanella, Marta, Puthanakit, Thanyawee, Leyre, Louise, Jupimai, Thidarat, Sawangsinth, Panadda, Souza, Mark de, Suntarattiwong, Piyarat, Kosalarksa, Pope, Borkird, Thitiporn, Kanjanavanit, Suparat, Chokephaibulkit, Kulkanya, Hansudewechakul, Rawiwan, Petdachai, Witaya, Mitchell, Julie L, Robb, Merlin L, Trautmann, Lydie, Ananworanich, Jintanat, Chomont, Nicolas, and Groups, RV474/HIVNAT194 and RV475/HIVNAT 209 Study
- Subjects
HIV infections ,DNA ,VIRAL load ,CROSS-sectional method ,ANTIRETROVIRAL agents ,RNA ,DESCRIPTIVE statistics ,PREVENTIVE medicine ,T cells ,VERTICAL transmission (Communicable diseases) ,LONGITUDINAL method ,CHILDREN - Abstract
Background Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. Methods We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. Results Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P <.020 and P <.001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. Conclusions Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
19. Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection
- Author
-
Pardons, Marion, primary, Baxter, Amy E., additional, Massanella, Marta, additional, Pagliuzza, Amélie, additional, Fromentin, Rémi, additional, Dufour, Caroline, additional, Leyre, Louise, additional, Routy, Jean-Pierre, additional, Kaufmann, Daniel E., additional, and Chomont, Nicolas, additional
- Published
- 2019
- Full Text
- View/download PDF
20. Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals
- Author
-
Uzzan, Mathieu, primary, Tokuyama, Minami, additional, Rosenstein, Adam K., additional, Tomescu, Costin, additional, SahBandar, Ivo N., additional, Ko, Huaibin M., additional, Leyre, Louise, additional, Chokola, Anupa, additional, Kaplan-Lewis, Emma, additional, Rodriguez, Gabriela, additional, Seki, Akihiro, additional, Corley, Michael J., additional, Aberg, Judith, additional, La Porte, Annalena, additional, Park, Eun-young, additional, Ueno, Hideki, additional, Oikonomou, Ioannis, additional, Doron, Itai, additional, Iliev, Iliyan D., additional, Chen, Benjamin K., additional, Lui, Jennifer, additional, Schacker, Timothy W., additional, Furtado, Glaucia C., additional, Lira, Sergio A., additional, Colombel, Jean-Frederic, additional, Horowitz, Amir, additional, Lim, Jean K., additional, Chomont, Nicolas, additional, Rahman, Adeeb H., additional, Montaner, Luis J., additional, Ndhlovu, Lishomwa C., additional, and Mehandru, Saurabh, additional
- Published
- 2018
- Full Text
- View/download PDF
21. The V2 loop of HIV gp120 delivers costimulatory signals to CD4+ T cells through Integrin α4β7 and promotes cellular activation and infection.
- Author
-
Goes, Livia R., Sajani, Alia, Sivro, Aida, Olowojesiku, Ronke, Ray, Jocelyn C., Perrone, Ian, Yolitz, Jason, Girard, Alexandre, Leyre, Louise, Wibmer, Constantinos Kurt, Morris, Lynn, Gorini, Giacomo, Franchini, Genoveffa, Mason, Rosemarie D., Roederer, Mario, Mehandru, Saurabh, Soares, Marcelo A., Cicala, Claudia, Fauci, Anthony S., and Arthos, James
- Subjects
T cells ,HIV infections ,INTEGRINS ,HIV infection transmission ,HIV - Abstract
Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4
+ T cells. Trafficking of α4 β7 -expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4 β7 that is expressed on gut endothelial cells. MAdCAM signaling through α4 β7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4 β7 . In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4 β7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4 β7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4 β7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
22. Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection.
- Author
-
Leyre, Louise, Kroon, Eugène, Vandergeeten, Claire, Sacdalan, Carlo, Colby, Donn J., Buranapraditkun, Supranee, Schuetz, Alexandra, Chomchey, Nitiya, de Souza, Mark, Bakeman, Wendy, Fromentin, Rémi, Pinyakorn, Suteeraporn, Akapirat, Siriwat, Trichavaroj, Rapee, Chottanapund, Suthat, Manasnayakorn, Sopark, Rerknimitr, Rungsun, Wattanaboonyoungcharoen, Phandee, Kim, Jerome H., and Tovanabutra, Sodsai
- Abstract
Clearing a path for an HIV cure: Curing HIV is more feasible if we better understand the formation of the latent viral reservoir. Leyre et al. studied longitudinal blood and tissue samples during acute HIV infection. The large pool of infected cells present at early stages did not survive antiretroviral treatment. Infected cells at later stages were more prevalent in lymphoid tissues than in blood. These results show that most infected targets are cleared with early treatment, but HIV
+ cells that remain after a certain stage are more likely to persist. These persistent cells are the ones that will need to be eradicated for a cure to be achieved. The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
23. Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size
- Author
-
Teigler, Jeffrey E., primary, Leyre, Louise, additional, Chomont, Nicolas, additional, Slike, Bonnie, additional, Jian, Ningbo, additional, Eller, Michael A., additional, Phanuphak, Nittaya, additional, Kroon, Eugène, additional, Pinyakorn, Suteeraporn, additional, Eller, Leigh Anne, additional, Robb, Merlin L., additional, Ananworanich, Jintanat, additional, Michael, Nelson L., additional, Streeck, Hendrik, additional, and Krebs, Shelly J., additional
- Published
- 2018
- Full Text
- View/download PDF
24. Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments.
- Author
-
Crowell, Trevor A, Colby, Donn J, Pinyakorn, Suteeraporn, Fletcher, James L K, Kroon, Eugène, Schuetz, Alexandra, Krebs, Shelly J, Slike, Bonnie M, Leyre, Louise, and Chomont, Nicolas
- Subjects
HIV infection complications ,AIDS ,HIV-positive persons ,PROBABILITY theory ,SYNDROMES ,VIRAL load ,ANTIRETROVIRAL agents ,TREATMENT effectiveness ,CD4 lymphocyte count ,PHARMACODYNAMICS - Abstract
Background. Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods. Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results. From 212 382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P < .05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P < .05) but other biomarkers equilibrated. Conclusions. ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
25. Selective BCL-XL Antagonists Eliminate Infected Cells from a Primary-Cell Model of HIV Latency but Not from Ex Vivo Reservoirs.
- Author
-
Yanqin Ren, Szu Han Huang, Macedo, Amanda B., Ward, Adam R., Alberto, Winiffer D. Conce, Klevorn, Thais, Leyre, Louise, Copertino, Dennis C., Mota, Talia M., Dora Chan, Truong, Ronald, Rohwetter, Thomas, Zumbo, Paul, Dündar, Friederike, Betel, Doron, Kovacs, Colin, Benko, Erika, Bosque, Alberto, and Jones, R. Brad
- Subjects
- *
HIV , *T cells , *BCL-2 proteins , *CELL survival , *CELL death , *ANTIRETROVIRAL agents , *HIV infections - Abstract
HIV persists, despite immune responses and antiretroviral therapy, in viral reservoirs that seed rebound viremia if therapy is interrupted. Previously, we showed that the BCL-2 protein contributes to HIV persistence by conferring a survival advantage to reservoir-harboring cells. Here, we demonstrate that many of the BCL-2 family members are overexpressed in HIV-infected CD41 T cells, indicating increased tension between proapoptotic and prosurvival family members--and suggesting that inhibition of prosurvival members may disproportionately affect the survival of HIV-infected cells. Based on these results, we chose to study BCL-XL due to its consistent overexpression and the availability of selective antagonists. Infection of primary CD41 T cells with HIV resulted in increased BCL-XL protein expression, and treatment with two selective BCL-XL antagonists, A-1155463 and A-1551852, led to selective death of productively infected CD41 T cells. In a primary cell model of latency, both BCL-XL antagonists drove reductions in HIV DNA and in infectious cell frequencies both alone and in combination with the latency reversing agent bryostatin-1, with little off-target cytotoxicity. However, these antagonists, with or without bryostatin-1 or in combination with the highly potent latency reversing agent combination phorbol myristate acetate (PMA) 1 ionomycin, failed to reduce total HIV DNA and infectious reservoirs in ex vivo CD41 T cells from antiretroviral therapy (ART)-suppressed donors. Our results add to growing evidence that bona fide reservoir-harboring cells are resistant to multiple "kick and kill" modalities--relative to latency models. We also interpret our results as encouraging further exploration of BCL-XL antagonists for cure, where combination approaches, including with immune effectors, may unlock the ability to eliminate ex vivo reservoirs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
26. Integrated assessment of viral transcription, antigen presentation, and CD8+ T cell function reveal multiple limitations of class I selective HDACi during HIV-1 latency reversal.
- Author
-
Mota, Talia M., McCann, Chase D., Danesh, Ali, Szu-Han Huang, Magat, Dean B., Yanqin Ren, Leyre, Louise, Bui, Tracy D., Rohwetter, Thomas M., Kovacs, Colin M., Benko, Erika, MacLaren, Lynsay, Wimpelberg, Avery, Cannon, Christopher C., Hardy, W. David, Safrit, Jeffrey T., and Jones, R. Brad
- Subjects
- *
T cells , *CELL physiology , *ANTIGEN presentation , *ANTIGEN presenting cells , *CLONE cells , *T cell receptors , *MUCOCILIARY system , *TRANSGENIC organisms - Abstract
Clinical trials investigating HDACi to reverse HIV-1 latency aim to expose reservoirs in antiretroviral-treated individuals to clearance by immune effectors, yet have not driven measurable reductions in the frequencies of infected cells. We therefore investigated the effects of the class-I-selective HDACi nanatinostat and romidepsin on various blocks to latency reversal and elimination, including viral splicing, antigen presentation, and CD8+ T cell function. In ex vivo CD4+ T cells from ARV-suppressed individuals, both HDACi significantly induced viral transcription but not splicing, nor supernatant HIV-1 RNA. In an HIV-1 latency model using autologous CD8+ T cell clones as biosensors of antigen presentation, neither HDACi-treated CD4+ T cell condition induced clone degranulation. Both HDACi also impaired the function of primary CD8+ T cells in viral inhibition assays, with less impairment using nanatinostat. These findings suggest spliced or cell-free HIV-1 RNA are more indicative of antigen expression than unspliced HIV-RNA, and may help to explain the limited abilities of HDACi to generate CD8+ T cell targets in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
27. HIV-1 infection is associated with depletion of germinal center B cells and a decrease in IgA + plasma cells in the GI tract.
- Author
-
Cossarini F, Shang J, Krek A, Al-Taie Z, Hou R, Canales-Herrerias P, Tokuyama M, Tankelevich M, Tillowiz A, Jha D, Livanos AE, Leyre L, Uzzan M, Martinez-Delgado G, Tylor M, Sharma K, Bourgonje AR, Cruz M, Ioannou G, Dawson T, D'Souza D, Kim-Schulze S, Akm A, Aberg JA, Chen BK, Gnjatic S, Polydorides AD, Cerutti A, Argmann C, Vujkovic-Cvijin I, Suarez-Farinas M, Petralia F, Faith JJ, and Mehandru S
- Abstract
Gastrointestinal (GI) B cells and plasma cells (PCs), critical to mucosal homeostasis, play an important role in the host response to HIV-1 infection. Here, high resolution mapping of human B cells and PCs from colon and ileum during both viremic and suppressed HIV-1 infection identified a significant reduction in germinal center (GC) B cells and Follicular Dendritic Cells (FDCs) during HIV-1 viremia. Further, IgA
+ PCs, the major cellular output of intestinal GCs were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling persisted in antiretroviral therapy (ART) treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations associated with changes in intestinal microbiome composition and systemic inflammation. Herein, we highlight a key immune defect in the GI mucosa due to HIV-1 viremia, with major implications., One Sentence Summary: Major perturbations in intestinal GC dynamics in viremic HIV-1 infection relate to reduced IgA+ plasma cells, systemic inflammation and microbiota changes.- Published
- 2024
- Full Text
- View/download PDF
28. The V2 loop of HIV gp120 delivers costimulatory signals to CD4 + T cells through Integrin α 4 β 7 and promotes cellular activation and infection.
- Author
-
Goes LR, Sajani A, Sivro A, Olowojesiku R, Ray JC, Perrone I, Yolitz J, Girard A, Leyre L, Wibmer CK, Morris L, Gorini G, Franchini G, Mason RD, Roederer M, Mehandru S, Soares MA, Cicala C, Fauci AS, and Arthos J
- Subjects
- Anti-HIV Agents immunology, Anti-HIV Agents pharmacology, Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Antibodies, Neutralizing immunology, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, Cell Proliferation, Epitopes immunology, Epitopes metabolism, HIV Envelope Protein gp120 chemistry, HIV Envelope Protein gp120 immunology, HIV Infections pathology, HIV Infections virology, Host-Pathogen Interactions physiology, Humans, Lymphocyte Activation, Protein Domains, Signal Transduction, Simian Immunodeficiency Virus immunology, Tretinoin pharmacology, CD4-Positive T-Lymphocytes virology, HIV Envelope Protein gp120 metabolism, HIV Infections metabolism, Integrins metabolism
- Abstract
Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4
+ T cells. Trafficking of α4 β7 -expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4 β7 that is expressed on gut endothelial cells. MAdCAM signaling through α4 β7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4 β7 In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4 β7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4 β7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4 β7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis., Competing Interests: The authors declare no competing interest.- Published
- 2020
- Full Text
- View/download PDF
29. Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals: Potential Role in Persistent Inflammation and Transcription From Stable HIV-1 Reservoirs.
- Author
-
Zaidan SM, Leyre L, Bunet R, Larouche-Anctil E, Turcotte I, Sylla M, Chamberland A, Chartrand-Lefebvre C, Ancuta P, Routy JP, Baril JG, Trottier B, MacPherson P, Trottier S, Harris M, Walmsley S, Conway B, Wong A, Thomas R, Kaplan RC, Landay AL, Durand M, Chomont N, Tremblay CL, and El-Far M
- Subjects
- Anti-HIV Agents therapeutic use, CD4-Positive T-Lymphocytes virology, Case-Control Studies, Drug Therapy, Combination, HIV Infections drug therapy, HIV-1 metabolism, Humans, Inflammation genetics, Inflammation metabolism, Interleukins genetics, Interleukins pharmacology, Leukocytes, Mononuclear, Protein Isoforms blood, Protein Isoforms genetics, Protein Isoforms pharmacology, Recombinant Proteins pharmacology, Transcription, Genetic drug effects, Up-Regulation, Viral Load, CD4-Positive T-Lymphocytes metabolism, HIV Infections blood, HIV-1 genetics, Interleukins blood
- Abstract
Background: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory., Setting and Methods: Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR., Results: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals., Conclusions: Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.