Editorial Material
Immunology
Sherazaan D. Ismail, Catherine Riou, Sarah B. Joseph, Nancie M. Archin, David M. Margolis, Alan S. Perelson, Tyler Cassidy, Melissa-Rose Abrahams, Matthew Moeser, Olivia D. Council, Lyle R. McKinnon, Farzana Osman, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald Swanstrom, Carolyn Williamson, Nigel J. Garrett, Wendy A. Burgers
Summary: Pretreatment CD8(+) T-cell activation, nadir CD4 count, and CD4:CD8 ratio were found to predict the size of the HIV-1 reservoir after 5 years of suppressive antiretroviral therapy initiated during chronic infection.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Cell Biology
Carl J. Balibar, Daniel J. Klein, Beata Zamlynny, Tracy L. Diamond, Zhiyu Fang, Carol A. Cheney, Jan Kristoff, Meiqing Lu, Marina Bukhtiyarova, Yangsi Ou, Min Xu, Lei Ba, Steven S. Carroll, Abdellatif El Marrouni, John F. Fay, Ashley Forster, Shih Lin Goh, Meigang Gu, Daniel Krosky, Daniel I. S. Rosenbloom, Payal Sheth, Deping Wang, Guoxin Wu, Matthias Zebisch, Tian Zhao, Paul Zuck, Jay Grobler, Daria J. Hazuda, Bonnie J. Howell, Antonella Converso
Summary: Antiretroviral therapy can inhibit HIV-1 replication but cannot cure the infection due to the persistence of a reservoir in the host genome. Reduction of this reservoir is important for HIV-1 cure. Some nonnucleoside reverse transcriptase inhibitors have shown selective cytotoxicity against HIV-1 in vitro, but their concentrations required are much higher than approved dosages. By focusing on this secondary activity, researchers have discovered bifunctional compounds called targeted activators of cell kill (TACK) that can kill HIV-1-infected cells at clinically achievable concentrations. These TACK molecules bind to the reverse transcriptase-p66 domain of monomeric Gag-Pol and act as allosteric modulators, promoting dimerization and premature intracellular viral protease activation, leading to death of HIV-1(+) cells. TACK molecules retain potent antiviral activity and selectively eliminate infected CD4(+) T cells, providing a potential immune-independent clearance strategy.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Hannah L. Itell, Daryl Humes, Julie Overbaugh
Summary: This study identifies new ISGs that inhibit HIV and confirms the role of certain factors in IFN restriction in T cells. The findings demonstrate the multifaceted nature of IFN restriction against HIV and establish a screening model for identifying HIV-restricting ISGs.
Article
Multidisciplinary Sciences
Basiel Cole, Laurens Lambrechts, Pierre Gantner, Ytse Noppe, Noah Bonine, Wojciech Witkowski, Lennie Chen, Sarah Palmer, James I. Mullins, Nicolas Chomont, Marion Pardons, Linos Vandekerckhove
Summary: The authors developed a single-cell approach, STIP-Seq, to simultaneously sequence TCR, integration sites, and proviral genomes, revealing that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5'-end of the genome. They also found that cell clones with predicted pathogen-specificity may harbor inducible proviruses.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Laurent Hany, Marc-Olivier Turmel, Corinne Barat, Michel Ouellet, Michel J. Tremblay
Summary: Although LRAs can efficiently reactivate latent CD4(+) T cells, their impact on HIV-1 infection and production in macrophages remains unclear. This study found that certain LRAs exhibit antireplicative features in human macrophages and identified a new viral production inhibition mechanism by bryostatin-1 specific to myeloid cells. Further research is needed to fully assess the efficacy of HIV-1 eradicating strategies.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Kien Nguyen, Curtis Dobrowolski, Meenakshi Shukla, Won-Kyung Cho, Benjamin Luttge, Jonathan Karn
Summary: The "block and lock" strategy for a functional cure of HIV-1 aims to permanently suppress the rebound of quiescent HIV-1 by epigenetic silencing. H3K27me3 and DNA methylation are associated with viral suppression, while H3K4me3 is correlated with viral expression. Inhibition of UTX/KDM6A can enhance H3K27me3 levels and increase DNA methylation to suppress latent HIV-1 reactivation in T cells.
Article
Medicine, Research & Experimental
Yik Lim Kok, Valentina Vongrad, Sandra E. Chaudron, Mohaned Shilaih, Christine Leemann, Kathrin Neumann, Katharina Kusejko, Francesca Di Giallonardo, Herbert Kuster, Dominique L. Braun, Roger D. Kouyos, Huldrych F. Gunthard, Karin J. Metzner
Summary: Characteristics of HIV-1 integration sites are established as early as during primary infection and are found in both resting and activated CD4(+) T cells. HIV-1 integration sites preferentially occur in specific genes and highly expressed genes, regardless of the activation state of CD4(+) T cells. The preference for cancer-related genes is more prominent at later stages of HIV-1 infection.
Article
Multidisciplinary Sciences
Paula C. Soto, Valeri H. Terry, Mary K. Lewinski, Savitha Deshmukh, Nadejda Beliakova-Bethell, Celsa A. Spina
Summary: This study investigates the relationship between T cell activation and proliferation and the establishment of HIV latency. The findings suggest that cells infected during the height of cell proliferation retain the least amount of latent infection, while cells that did not divide or exhibited limited division after virus exposure and stimulation contained greater amounts of latent HIV. Co-culture experiments demonstrate that latent infection can be established directly in non-dividing cells through cell-to-cell transmission.
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
Virology
Michelle E. Wong, Chad J. Johnson, Anna C. Hearps, Anthony Jaworowski
Summary: In this study, a robust experimental model was established to quantify and investigate HIV reactivation in latently infected macrophages, showing that different macrophage phenotypes, cellular and tissue environments influence HIV reactivation. Additionally, the study demonstrated that certain latency-reversing agents may have different effects on latently infected macrophages compared to T cells, suggesting the need for dedicated strategies to target these populations in vivo.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Ann-Kathrin Reuschl, Dejan Mesner, Maitreyi Shivkumar, Matthew V. X. Whelan, Laura J. Pallett, Jose Afonso Guerra-Assuncao, Rajhmun Madansein, Kaylesh J. Dullabh, Alex Sigal, John P. Thornhill, Carolina Herrera, Sarah Fidler, Mahdad Noursadeghi, Mala K. Maini, Clare Jolly
Summary: HIV-1 can infect resting memory T cells through cell-to-cell spread, and the infection leads to a reprogramming of T cells, acquiring characteristics of tissue-resident memory T cells.
Article
Medicine, Research & Experimental
Kim Anthony-Gonda, Alex Ray, Hang Su, Yuge Wang, Ying Xiong, Danica Lee, Ariele Block, Vanessa Chilunda, Jessica Weiselberg, Lily Zemelko, Yen Y. Wang, Sarah Kleinsorge-Block, Jane S. Reese, Marcos de Lima, Christina Ochsenbauer, John C. Kappes, Dimiter S. Dimitrov, Rimas Orentas, Steven G. Deeks, Rachel L. Rutishauser, Joan W. Berman, Harris Goldstein, Boro Dropulic
Summary: HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapy holds promise for curing HIV infection by eliminating infected cells. The study shows that anti-HIV duoCAR T cells can localize to lymphoid tissues and eliminate HIV-infected cells. Furthermore, the therapy effectively senses and kills HIV-infected CD4+ T cells and monocytes/macrophages.
Article
Microbiology
Helene Bauby, Christopher C. Ward, Rupert Hugh-White, Chad M. Swanson, Reiner Schulz, Caroline Goujon, Michael H. Malim
Summary: The interaction between HIV-1 and CD4(+) T cells have been studied through transcriptomics analysis, unveiling global changes in gene expression. The viral accessory protein Vpr plays a crucial role in these gene expression changes, highlighting its significance in infection and pathogenesis. This finding sheds new light on the interplay between HIV-1 and its host at the cellular level.
Article
Virology
Jie Lan, Wei Li, Richard Yu, Fahim Syed, Qigui Yu
Summary: This article investigates the kinetics and mechanisms of HIV-1 protein expression, virion production, and cell-to-cell virus transmission during provirus reactivation. The study finds that HIV-1 transmission through cell-to-cell contact is more efficient than cell-free spread and relies on the presence of Env on the cell surface and F-actin remodeling. Resting CD4(+) T cells, especially memory cells, are highly susceptible to HIV-1 infection via cell-to-cell transmission. Protease inhibitors and neutralizing antibodies targeting the CD4-binding site can significantly reduce HIV-1 cell-to-cell transmission.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Biology
Mie Kobayashi-Ishihara, Katarina Frazao Smutna, Florencia E. Alonso, Jordi Argilaguet, Anna Esteve-Codina, Kerstin Geiger, Meritxell Genesca, Judith Grau-Exposito, Clara Duran-Castells, Selina Rogenmoser, Rene Boettcher, Jennifer Jungfleisch, Baldomero Oliva, Javier P. Martinez, Manqing Li, Michael David, Makoto Yamagishi, Marta Ruiz-Riol, Christian Brander, Yasuko Tsunetsugu-Yokota, Maria J. Buzon, Juana Diez, Andreas Meyerhans
Summary: In cell lines and HIV-1 patient PBMCs, the Schlafen 12 protein (SLFN12) is shown to be an HIV-1 restriction factor that inhibits HIV-1 replication and virus reactivation. SLFN12 establishes a post-transcriptional block in HIV-1-infected cells, dependent on the HIV-1 codon usage and its RNase active sites. SLFN12 expression in PBMCs of HIV-1-infected individuals correlates with viral loads.
COMMUNICATIONS BIOLOGY
(2023)
Review
Immunology
John Michael S. Sanchez, Ana Beatriz DePaula-Silva, Jane E. Libbey, Robert S. Fujinami
CLINICAL IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Jozefien De Clercq, Sofie Rutsaert, Marie-Angelique De Scheerder, Chris Verhofstede, Steven Callens, Linos Vandekerckhove
Summary: Initiating ART during acute HIV infection has significant benefits for individuals, society, and future HIV cure research. Early diagnosis should be equally emphasized to implement this strategy.
ACTA CLINICA BELGICA
(2022)
Article
Biochemical Research Methods
Willem van Snippenberg, David Gleerup, Sofie Rutsaert, Linos Vandekerckhove, Ward De Spiegelaere, Wim Trypsteen
Summary: The development of an HIV-1 cure is hindered by the presence of a persistent reservoir of intact proviruses. It is crucial to accurately evaluate and quantify these proviruses to determine the efficacy of HIV-1 cure strategies. This study presents two triplex digital PCR assays and validates their performance in detecting HIV-1 reservoirs.
Article
Pharmacology & Pharmacy
Erin T. Larragoite, Racheal A. Nell, Laura J. Martins, Louis R. Barrows, Vicente Planelles, Adam M. Spivak
Summary: Latency reversing agents such as PKC agonists hold promise for eliminating HIV-1 latent reservoir, but can induce harmful proinflammatory cytokine production. Adjuvant pharmacological agents like JAK inhibitors have been used to reduce pro-inflammatory cytokine secretion without inhibiting HIV-1 reactivation. HDAC inhibitors are known to dampen proinflammatory cytokine secretion and can synergize with LRAs, but may not significantly reactivate latent HIV-1.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Veterinary Sciences
Nadia Ayurini Anantama, Charis Du Cheyne, Ann Martens, Susanne Pauline Roth, Janina Burk, Ward De Spiegelaere, Jule Kristin Michler
Summary: Exuberant granulation tissue (EGT) is commonly observed in horses during second intention wound healing. The mechanisms leading to EGT are still unclear, and effective strategies to prevent and treat EGT are lacking. This study conducted a systematic search and scoping review to consolidate the literature on EGT and identify knowledge gaps and research opportunities. The results highlight the need for evidence-based recommendations on EGT treatment and the importance of incorporating basic research knowledge into clinical trials.
VETERINARY JOURNAL
(2022)
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
Infectious Diseases
Sofie Rutjens, Nick Vereecke, Ward De Spiegelaere, Siska Croubels, Mathias Devreese
Summary: Optimizing antimicrobial treatment during bacterial infections in livestock requires a deep understanding of the impact of such treatment on the pathogen and commensal microbiota. This study investigated the excretion of ceftiofur and cefquinome in the gut and feces of pigs after intramuscular administration. The findings provide valuable information on the gut excretion of these antimicrobials.
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
Oncology
Jonas Steenbrugge, Julie Bellemans, Niels Vander Elst, Kristel Demeyere, Josephine De Vliegher, Timothy Perera, Olivier De Wever, Wim Van Den Broeck, Ward De Spiegelaere, Niek N. Sanders, Evelyne Meyer
Summary: This study examines the immunomodulatory effects of cisplatin in triple-negative breast cancer (TNBC). The results show that cisplatin not only directly kills tumor cells but also stimulates anti-tumor immunity, reducing disease progression. These immunomodulatory effects are established after the first dose of cisplatin and can provide durable immunostimulation, even after a single dose.
Article
Immunology
Thessa Laeremans, Sigrid D'haese, Jonathan Aernout, Kurt Barbe, Pieter Pannus, Sofie Rutsaert, Ellen Vancutsem, Guido Vanham, Coca Necsoi, Ward De Spiegelaere, Marie Couttenye, Natacha Herssens, Marie-Angelique De Scheerder, Stephane De Wit, Linos Vandekerckhove, Eric Florence, Joeri L. Aerts, Sabine D. Allard
Summary: This study investigates the use of qualitative plasma viral load (pVL) measurements to estimate viral reservoir size. The results show a positive correlation between t-DNA and the qualitative pVL measurements. Patients with a smaller viral reservoir have significantly lower qualitative pVL measurements. The study also suggests that t-DNA can be detected whenever the qualitative pVL measurements are higher than 56%.
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
Medical Laboratory Technology
Matthijs Vynck, Yao Chen, David Gleerup, Jo Vandesompele, Wim Trypsteen, Antoon Lievens, Olivier Thas, Ward De Spiegelaere
Summary: Background partition classification is essential in digital PCR data analysis. This review provides an overview of available methods and their challenges, serving as a guide for practitioners. Strengths, weaknesses, and application gaps are discussed, stimulating method development.
CLINICAL CHEMISTRY
(2023)
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.
Meeting Abstract
Cell & Tissue Engineering
Marguerite Meeremans, Lana Van Damme, Ward De Spiegelaere, Mario Van Poucke, Luc Peelman, Sandra Van Vlierberghe, Catharina De Schauwer
TISSUE ENGINEERING PART A
(2022)