Article
Biology
Jinfeng Cai, Hongbo Gao, Jiacong Zhao, Shujing Hu, Xinyu Liang, Yanyan Yang, Zhuanglin Dai, Zhongsi Hong, Kai Deng
Summary: The research successfully established a highly physiologically relevant HIV-1 latency model by using a newly designed dual fluorescent reporter virus DFV-B, which can directly label latently infected cells and identified ACY-1215 as a potent latency reversing agent through high-throughput screening. This model provides a valuable tool to study critical events of HIV-1 latency and explore potential functional cures for AIDS.
Article
Immunology
Anne Inderbitzin, Tom Loosli, Lennart Opitz, Peter Rusert, Karin J. Metzner
Summary: The main obstacle to curing HIV-1 is the latent reservoir. Understanding the mechanism of HIV-1 latency and reactivation through CD4(+) T cell models is crucial. Recent studies have used transcriptome analysis to identify differentially expressed genes in latently- and reactivated HIV-1 infected cells, providing insights into HIV-1 latency.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Michelle Y-H Lee, Georges Khoury, Moshe Olshansky, Secondo Sonza, Glen P. Carter, James McMahon, Timothy P. Stinear, Stephen J. Turner, Sharon R. Lewin, Damian F. J. Purcell
Summary: Latent HIV-1 provirus in individuals on suppressive therapy can be transcriptionally active and generate chimeric mRNA through readthrough transcription and aberrant splicing. Activation of the 3'LTR and cryptic splice donor site in the 5'LTR of HIV-1 leads to the formation of chimeric cellular:HIV mRNA. Understanding the characteristics of HIV-1 integrants that promote chimeric mRNA formation provides insights into the HIV-1 RNA footprint in latently infected cells.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Summary: The persistence of latent HIV provirus pools in different resting CD4+ cell subsets poses the greatest obstacle in current HIV treatment and cure efforts. Recent attempts to flush out latently infected memory CD4+ T-cells using latency-reversing agents have been unsuccessful in clinical trials. The major limitations of current approaches using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells are discussed in this review, along with potential solutions to these limitations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Abigail E. Schiff, Alice H. Linder, Shillah N. Luhembo, Stephanie Banning, Martin J. Deymier, Thomas J. Diefenbach, Amy K. Dickey, Athe M. Tsibris, Alejandro B. Balazs, Josalyn L. Cho, Benjamin D. Medoff, Gerhard Walzl, Robert J. Wilkinson, Wendy A. Burgers, Bjoern Corleis, Douglas S. Kwon
Summary: The study found that T-tropic HIV exists in alveolar macrophages (AMs) of HIV-infected individuals, entering macrophages through contact with infected CD4+T cells, leading to AM infection. Despite the low efficiency of cell-free infection in macrophages, the CD4+T cell-dependent entry of HIV helps explain the presence of HIV in AMs.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Reou Tanabe, Yuko Morikawa
Summary: The study demonstrated that latently HIV-1-infected cells have enhanced cell adhesion and transendothelial migration abilities, suggesting their potential for efficient homing to lymph nodes.
Article
Microbiology
Maria Pino, Susan Pereira Ribeiro, Amelie Pagliuzza, Khader Ghneim, Anum Khan, Emily Ryan, Justin L. Harper, Colin T. King, Sarah Welbourn, Luca Micci, Sol Aldrete, Keith A. Delman, Theron Stuart, Michael Lowe, Jason M. Brenchley, Cynthia A. Derdeyn, Kirk Easley, Rafick P. Sekaly, Nicolas Chomont, Mirko Paiardini, Vincent C. Marconi
Summary: Clinical outcomes are inferior in individuals with HIV experiencing suboptimal CD4 T-cell recovery during ART. The study found that immunologic suboptimal responders (ISR) had higher HIV-DNA levels in multiple CD4 T-cell subsets and higher expression of PD-1 and TIGIT exclusively on CM and TM CD4 T-cells pre-ART, indicating higher HIV reservoir maintenance. Additionally, ISR showed a lack of response to IL-7 and IL-15, potentially contributing to suboptimal CD4 T-cell recovery during ART.
Article
Multidisciplinary Sciences
Wanwisa Promsote, Ling Xu, Jason Hataye, Giulia Fabozzi, Kylie March, Cassandra G. Almasri, Megan E. DeMouth, Sarah E. Lovelace, Chloe Adrienna Talana, Nicole A. Doria-Rose, Krisha McKee, Sabrina Helmold Hait, Joseph P. Casazza, David Ambrozak, Jochen Beninga, Ercole Rao, Norbert Furtmann, Joerg Birkenfeld, Elizabeth McCarthy, John-Paul Todd, Constantinos Petrovas, Mark Connors, Andrew T. Hebert, Jeremy Beck, Junqing Shen, Bailin Zhang, Mikhail Levit, Ronnie R. Wei, Zhi-yong Yang, Amarendra Pegu, John R. Mascola, Gary J. Nabel, Richard A. Koup
Summary: Researchers have developed a trispecific antibody that can activate and target latently HIV-1 infected cells for elimination by T cells, providing an alternative strategy for curing HIV.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Eun Hye Kim, Lara Manganaro, Michael Schotsaert, Brian D. Brown, Lubbertus C. F. Mulder, Viviana Simon
Summary: There is no cure for HIV infection due to the establishment of a latent reservoir that escapes antiretroviral treatments. A viral vector has been developed to accurately identify cells with latent proviruses and reveal mechanisms of latency establishment.
CELL REPORTS METHODS
(2022)
Article
Medicine, Research & Experimental
Francesco R. Simonetti, Hao Zhang, Garshasb P. Soroosh, Jiayi Duan, Kyle Rhodehouse, Alison L. Hill, Subul A. Beg, Kevin McCormick, Hayley E. Raymond, Christopher L. Nobles, John K. Everett, Kyungyoon J. Kwon, Jennifer A. White, Jun Lai, Joseph B. Margolick, Rebecca Hoh, Steven G. Deeks, Frederic D. Bushman, Janet D. Siliciano, Robert F. Siliciano
Summary: The study highlights that antigen-driven clonal selection plays a major role in HIV-1 persistence, posing a difficult challenge for eradication efforts. The research demonstrates a link between antigen responsiveness, proviral sequence, integration site, and TCR beta sequence in understanding the mechanisms behind maintaining the HIV-1 reservoir.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
E. A. Innis, C. Levinger, M. A. Szaniawski, E. S. C. P. Williams, J. Alcami, A. Bosque, J. T. Schiffer, M. Coiras, A. M. Spivak, V Planelles
Summary: This study investigated FDA-approved oncology drugs and found that dasatinib, ponatinib, and trametinib can significantly reduce proliferation of memory CD4 T cells in HIV-infected individuals. Dasatinib, in particular, blocks both homeostatic and antigen-driven proliferation and aids in reducing the reservoir size. By inhibiting STAT5 phosphorylation, dasatinib hinders IL-7 induced proliferation and prevents spontaneous rebound in cells from people living with HIV-1.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haruki Kitamura, Sayaka Sukegawa, Kouki Matsuda, Kousuke Tanimoto, Takuya Kobayakawa, Kazuho Takahashi, Hirokazu Tamamura, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Kenji Maeda, Hiroaki Takeuchi
Summary: Combinational antiretroviral therapy (cART) successfully suppresses viral load but fails to eliminate HIV-1 reservoirs. "Shock and Kill" strategy using latently-reversing agents (LRAs) is being developed to reactivate latent HIV-1 and induce cell death. This study identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate that effectively reactivated HIV-1 and induced cell death in latently-infected cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Virology
Sepideh Saeb, Mehrdad Ravanshad, Mahmoud Reza Pourkarim, Fadoua Daouad, Kazem Baesi, Olivier Rohr, Clementine Wallet, Christian Schwartz
Summary: This paper discusses the importance of reducing HIV-1 reservoirs in achieving a functional cure, with a focus on the challenges of targeting infected microglial cells in the brain. The study introduces an original gene suicide strategy using latently infected microglial cells as model cells to address the difficulty of eradicating these reservoirs.
Article
Immunology
Isobel Okoye, Lai Xu, Olaide Oyegbami, Shima Shahbaz, Desmond Pink, Priscilla Gao, Xuejun Sun, Shokrollah Elahi
Summary: The study suggests that plasma extracellular vesicles can enhance HIV infection and reactivate latent virus through the regulation of miR-139-5p. This miRNA can impact cell activation by modulating the expression levels of transcription factors and immune-related genes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Alexander Dowell, Tracey Haigh, Gordon Ryan, James Turner, Heather Long, Graham Taylor
Summary: Epstein Barr Virus (EBV) infects a large percentage of the population and establishes latent infection in B-cells. Efforts to develop EBV prophylactic vaccination have mainly focused on neutralising antibodies, but generating T-cell responses against EBV structural proteins could be a promising alternative strategy. Research has shown that EBV capsid proteins BcLF1, BDLF1, and BORF1 are frequent targets of T-cell responses, and CD4+ T-cells specific for these proteins can recognize and control newly EBV-infected cells, even in long-term viral carriage. This study highlights the potential of targeting structural antigens for prophylactic EBV vaccine development.
Article
Medicine, Research & Experimental
Yanqin Ren, Szu Han Huang, Shabnum Patel, Winiffer D. Conce Alberto, Dean Magat, Dughan Ahimovic, Amanda B. Macedo, Ryan Durga, Dora Chan, Elizabeth Zale, Talia M. Mota, Ronald Truong, Thomas Rohwetter, Chase D. McCann, Colin M. Kovacs, Erika Benko, Avery Wimpelberg, Christopher Cannon, W. David Hardy, Alberto Bosque, Catherine M. Bollard, R. Brad Jones
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Microbiology
Eric S. Sorensen, Amanda B. Macedo, Rachel S. Resop, J. Natalie Howard, Racheal Nell, Indra Sarabia, Daniel Newman, Yanqin Ren, R. Brad Jones, Vicente Planelles, Adam M. Spivak, Alberto Bosque
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Immunology
Ashley I. Heinson, Jeongmin Woo, Amey Mukim, Cory H. White, Bastiaan Moesker, Alberto Bosque, Celsa A. Spina, Christopher H. Woelk, Ben D. Macarthur, Nadejda Beliakova-Bethell
Summary: Despite significant progress in identifying cellular factors and pathways contributing to the latent HIV reservoir, the major obstacle to eradicating the virus remains. Noncoding genes, including microRNAs, have been implicated in regulating HIV expression during latency. This study revealed dysregulation of miRNAs in a primary CD4(+) T cell model of HIV latency, with a subset targeting pathways relevant to HIV expression and establishment of latency, such as the p53 signaling pathway.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2021)
Article
Virology
Indra Sarabia, Szu-Han Huang, Adam R. Ward, R. Brad Jones, Alberto Bosque
Summary: The establishment of HIV-1 latency has posed challenges for curing HIV-1. Current strategies to shock and kill the virus reservoir are not effective in inducing the majority of intact HIV-1 proviruses. The mechanisms behind the non-inducible HIV-1 reservoir still need further investigation.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Yanqin Ren, Szu Han Huang, Amanda B. Macedo, Adam R. Ward, Winiffer D. Conce Alberto, Thais Klevorn, Louise Leyre, Dennis C. Copertino, Talia M. Mota, Dora Chan, Ronald Truong, Thomas Rohwetter, Paul Zumbo, Friederike Dundar, Doron Betel, Colin Kovacs, Erika Benko, Alberto Bosque, R. Brad Jones
Summary: Research has shown that overexpression of BCL-X-L family members in HIV-infected CD4(+) T cells, selective antagonists can induce selective toxicity to these cells, however, the effect on reservoir cells in patients remains limited.
JOURNAL OF VIROLOGY
(2021)
Editorial Material
Immunology
Maria Salgado, Alberto Bosque, Carolina Garrido
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Indra Sarabia, Camille L. Novis, Amanda B. Macedo, Hiroshi Takata, Racheal Nell, Juyeon C. Kakazu, Robert L. Furler, Binita Shakya, Heidi L. Schubert, Christopher P. Hill, Ana Beatriz DePaula-Silva, Adam M. Spivak, Lydie Trautmann, Vicente Planelles, Alberto Bosque
Summary: Research has shown that RIG-I agonists require full length-MAVS, while the AOS response induced by Dynasore through its catechol group can reactivate latent HIV-1 in a MAVS dependent manner through miniMAVS isoform. Furthermore, PKC agonists induce an AOS response in CD4 T cells and require miniMAVS to fully reactivate latent HIV-1.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
E. A. Innis, C. Levinger, M. A. Szaniawski, E. S. C. P. Williams, J. Alcami, A. Bosque, J. T. Schiffer, M. Coiras, A. M. Spivak, V Planelles
Summary: This study investigated FDA-approved oncology drugs and found that dasatinib, ponatinib, and trametinib can significantly reduce proliferation of memory CD4 T cells in HIV-infected individuals. Dasatinib, in particular, blocks both homeostatic and antigen-driven proliferation and aids in reducing the reservoir size. By inhibiting STAT5 phosphorylation, dasatinib hinders IL-7 induced proliferation and prevents spontaneous rebound in cells from people living with HIV-1.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Callie Levinger, J. Natalie Howard, Jie Cheng, Pingtao Tang, Amit Joshi, Marta Catalfamo, Alberto Bosque
Summary: The assessment of HIV-1 persistence is challenging, with most commercially available tests focusing on the measurement of nucleic acid. Despite their high sensitivity, these assays have limitations in evaluating translational competent viral reservoirs.
SCIENTIFIC REPORTS
(2021)
Correction
Multidisciplinary Sciences
Callie Levinger, J. Natalie Howard, Jie Cheng, Pingtao Tang, Amit Joshi, Marta Catalfamo, Alberto Bosque
SCIENTIFIC REPORTS
(2021)
Article
Virology
Rachel S. Resop, Alberto Bosque
Summary: Inhibition of SPHK can reduce HIV-1 transmission between CD4 T cells and decrease susceptibility to infection, which may serve as a basis for developing strategies to prevent HIV-1 infection.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Amanda B. Macedo, Callie Levinger, Bryan N. Nguyen, Jonathan Richard, Mamta Gupta, Conrad Russell Y. Cruz, Andres Finzi, Katherine B. Chiappinelli, Keith A. Crandall, Alberto Bosque
Summary: In this study, we found that HODHBt enhances IL-15 signaling in natural killer cells, leading to increased cytotoxicity and memory-like functions. This suggests that pharmacological enhancement of IL-15-mediated STAT activation could be a new approach for HIV treatment.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Eva M. Stevenson, Sandra Terry, Dennis Copertino, Louise Leyre, Ali Danesh, Jared Weiler, Adam R. Ward, Pragya Khadka, Evan McNeil, Kevin Bernard, Itzayana G. Miller, Grant B. Ellsworth, Carrie D. Johnston, Eli J. Finkelsztein, Paul Zumbo, Doron Betel, Friederike Dundar, Maggie C. Duncan, Hope R. Lapointe, Sarah Speckmaier, Nadia Moran-Garcia, Michelle Premazzi Papa, Samuel Nicholes, Carissa J. Stover, Rebecca M. Lynch, Marina Caskey, Christian Gaebler, Tae-Wook Chun, Alberto Bosque, Timothy J. Wilkin, Guinevere Q. Lee, Zabrina L. Brumme, R. Brad Jones
Summary: In a cohort of people with HIV, COVID mRNA vaccination leads to a temporary increase in a specific profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA, indicating productive immune engagement with infected cells.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Preethi B. Balakrishnan, Carissa S. Holmberg, Debbie K. Ledezma, Alberto Bosque, Rohan Fernandes
Summary: This study investigates the use of nanoparticles as carriers to deliver drugs for the reactivation of latent HIV infection. The results show that polymeric-coated nanoparticles are more effective than free polymers in activating latent HIV and enhancing immune activation.
Review
Virology
J. Natalie Howard, Alberto Bosque
Summary: Despite advances in antiretroviral therapy, the latent reservoir of HIV-infected cells remains a major hurdle in finding a cure. IL-15 and N-803 have shown potential in reactivating latent HIV and enhancing immune effector function, which are crucial for reducing latent reservoirs.