Article
Biochemistry & Molecular Biology
Sergi Chumillas, Saurabh Loharch, Manuela Beltran, Mateusz P. Szewczyk, Silvia Bernal, Maria C. Puertas, Javier Martinez-Picado, Jose Alcami, Luis M. Bedoya, Vicente Marchan, Jose Gallego
Summary: This study explored the optimization of the antiretroviral properties of benfluron and found that both the benzo[c] and cyclopentanone components are essential for its activity. The results provide insights for the design of new anti-HIV agents targeting the inhibition of Rev function.
Article
Pharmacology & Pharmacy
Alvaro Simba-Lahuasi, Jose Alcami, Manuela Beltran, Luis M. Bedoya, Jose Gallego
Summary: A virtual compound screening identified new chemical scaffolds that can block the interaction between HIV-1 and RRE-Rev. These compounds inhibit the complex formation by binding to the RRE and show antiretroviral activity.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Virology
YoungHyun Shin, Chul Min Park, Hong Gi Kim, Dong-Eun Kim, Min Suk Choi, Jeong-ah Kim, Byeong-Sun Choi, Cheol-Hee Yoon
Summary: The study identified an aristolactam derivative with potent anti-HIV-1 effects and investigated the differing effects of residue substitutions on HIV-1 infection and cell viability through a structure-activity relationship study.
Article
Microbiology
Mollie M. McDonnell, Suzanne C. Karvonen, Amit Gaba, Ben Flath, Linda Chelico, Michael Emerman
Summary: The study demonstrated that synthetic A3C/A3H double deaminase domain proteins exhibit stronger antiviral activity against HIV-1 compared to A3G, with a mechanism that involves both deaminase-independent actions and enhanced RNA binding affinity.
Article
Microbiology
Michael Roling, Mahsa Mollapour Sisakht, Enrico Ne, Panagiotis Moulos, Raquel Crespo, Mateusz Stoszko, Elisa De Crignis, Helen Bodmer, Tsung Wai Kan, Maryam Akbarzadeh, Vaggelis Harokopos, Pantelis Hatzis, Robert-Jan Palstra, Tokameh Mahmoudi
Summary: This study identified novel host factors contributing to HIV-1 latency through genetic screening, including CHD9 which maintains latency by direct association with the HIV-1 5' LTR. FDA-approved inhibitors targeting ADK, NF1, and GRIK5 were characterized for their latency reversal potential, with topiramate showing promise as a latency reversal agent with clinical potential for individuals living with HIV-1 under suppressive antiretroviral therapy.
Article
Microbiology
Yuki Kurebayashi, Shringkhala Bajimaya, Masahiro Watanabe, Nicholas Lim, Michael Lutz, Megan Dunagan, Toru Takimoto
Summary: This study investigated the interaction of human parainfluenza viruses type 1 (hPIV1) and type 3 (hPIV3) with human airway cells. The results showed that hPIV1 infection downregulated cholesterol-related genes, induced ISGs stronger than hPIV3, and led to ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, disrupting formation of cholesterol-rich lipid rafts in infected cells. These findings suggest that hPIV1 has the ability to regulate cholesterol biogenesis, which along with ISGs, contributes to the establishment of quiescent infection.
Article
Microbiology
Han Xiao, Emanuel Wyler, Miha Milek, Bastian Grewe, Philipp Kirchner, Arif Ekici, Ana Beatriz Oliveira Villela Silva, Doris Jungnickl, Florian Full, Marco Thomas, Markus Landthaler, Armin Ensser, Klaus Ueberla
Summary: The HIV-1 Rev protein is crucial for nuclear export of unspliced and incompletely spliced HIV-1 RNAs. Depletion of proteins like CRNKL1 can significantly enhance levels of unspliced HIV-1 RNA in the cytoplasm, potentially revealing a cellular mechanism exploited by HIV-1 to regulate its complex splicing pattern.
Article
Multidisciplinary Sciences
Viviana Cobos Jimenez, Aviva Geretz, Andrey Tokarev, Philip K. Ehrenberg, Selase Deletsu, Kawthar Machmach, Prakriti Mudvari, J. Natalie Howard, Amanda Zelkoski, Dominic Paquin-Proulx, Gregory Q. Del Prete, Caroline Subra, Eli A. Boritz, Alberto Bosque, Rasmi Thomas, Diane L. Bolton
Summary: AP-1 transcription factor plays an important role in latent HIV-1 infection and reactivation. Inhibiting AP-1 may be a potential therapeutic approach to limit HIV-1 reservoirs.
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
Jonathan M. O. Rawson, Olga A. Nikolaitchik, Saurabh Shakya, Brandon F. Keele, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 selectively packages specific unspliced RNA species during genome packaging, and this mechanism is conserved in various primate lentiviruses.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Andrew Atkinson, Marcel Zwahlen, Diana Barger, Antonella d'Arminio Monforte, Stephane De Wit, Jade Ghosn, Enrico Girardi, Veronica Svedhem, Philippe Morlat, Cristina Mussini, Antoni Noguera-Julian, Christoph Stephan, Giota Touloumi, Ole Kirk, Amanda Mocroft, Peter Reiss, Jose M. Miro, James R. Carpenter, Hansjakob Furrer
Summary: The study suggests that primary prophylaxis for pneumocystis pneumonia (PcP) may be safely withheld in confirmed virologically suppressed patients on antiretroviral therapy (ART), regardless of their CD4 count.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Bradley R. Jones, Jeffrey B. Joy
Summary: This study explores Bayesian methods using BEAST2 software to estimate the integration dates of HIV proviruses in the persistent reservoir. By collecting HIV sequences during suppressive therapy and implementing a tip date random walker and a latency-specific prior, the researchers were able to accurately estimate the integration dates. The Bayesian method outperforms previous techniques and provides an adaptable framework for inferring proviral integration dates.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Virology
Ling Ma, Shumin Chen, Zhen Wang, Saisai Guo, Jianyuan Zhao, Dongrong Yi, Quanjie Li, Zhenlong Liu, Fei Guo, Xiaoyu Li, Pingping Jia, Jiwei Ding, Chen Liang, Shan Cen
Summary: CRTCs can inhibit HIV-1 transcription and decrease viral RNA expression, having a negative impact on HIV-1 infection, and may drive HIV-1 into latency.
Article
Virology
Sarwat Zgheib, Nedal Taha, Manon Zeiger, Thiebault Lequeu, Oleksandr Glushonkov, Halina Anton, Pascal Didier, Emmanuel Boutant, Yves Mely, Eleonore Real
Summary: The specific interaction between HIV-1 nucleocapsid protein (NCp7) and human nucleolar protein 12 (hNoL12) in the nucleolus was confirmed. This interaction takes place in the subcellular compartment where NCp7 accumulates. This study is important for understanding the molecular mechanism of HIV-1 infection.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Alice Duchon, Steven Santos, Jianbo Chen, Matthew Brown, Olga A. Nikolaitchik, Sheldon Tai, Jeffrey A. Chao, Eric O. Freed, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 Gag selects and packages the HIV RNA genome during virus assembly, with multimerization and plasma membrane anchoring properties playing critical roles in efficient genome packaging. Studying these properties can provide insights into the mechanisms of viral RNA packaging and assembly of infectious virions.
Article
Microbiology
Judith Grau-Exposito, David Perea, Marina Suppi, Nuria Massana, Ander Vergara, Maria Jose Soler, Benjamin Trinite, Julia Blanco, Javier Garcia-Perez, Jose Alcami, Anna Serrano-Mollar, Joel Rosado, Vicenc Falco, Meritxell Genesca, Maria J. Buzon
Summary: We developed a rapid platform for studying SARS-CoV-2 by using primary human lung tissue cells directly, which can identify viral targets, express viral entry factors, and screen viral entry inhibitors and anti-inflammatory compounds. The method preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2, and maintains the expression of proteins involved in viral infection. Additionally, the method allows for highly reproducible antiviral testing and provides the identification of new compounds missed by conventional systems like VeroE6.
Article
Medicine, General & Internal
Sara Rodriguez-Mora, Magdalena Corona, Montserrat Torres, Guiomar Casado-Fernandez, Javier Garcia-Perez, Fernando Ramos-Martin, Lorena Vigon, Mario Manzanares, Elena Mateos, Fernando Martin-Moro, Alejandro Zurdo-Castronuno, Maria Aranzazu Murciano-Anton, Jose Alcami, Mayte Perez-Olmeda, Javier Lopez-Jimenez, Valentin Garcia-Gutierrez, Mayte Coiras
Summary: Patients with oncohematological diseases may have impaired immune response against vaccines due to their disease or treatment characteristics. While humoral response against SARS-CoV-2 was found to be suboptimal in these patients, cellular immune response appeared to be enhanced, especially in individuals with certain types of OHD such as chronic myeloid leukemia and chronic lymphocytic leukemia. Further analysis of immune response to subsequent vaccine doses will help determine the efficacy of COVID-19 vaccines in individuals with OHD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Lorena Vigon, Adrian Sanchez-Tornero, Sara Rodriguez-Mora, Javier Garcia-Perez, Magdalena Corona de Lapuerta, Lucia Perez-Lamas, Guiomar Casado-Fernandez, Gemma Moreno, Montserrat Torres, Elena Mateos, Maria Aranzazu Murciano-Anton, Jose Alcami, Mayte Perez-Olmeda, Javier Lopez-Jimenez, Valentin Garcia-Gutierrez, Mayte Coiras
Summary: Oncohematological patients have a reduced immune response to SARS-CoV-2, both from natural infection and vaccination. This study examined the immune response in individuals who underwent chemotherapy and autologous stem cell transplantation (ASCT) after natural infection. It was found that the humoral response was limited prior to ASCT, but an enhanced cellular immune response was observed after chemotherapy plus ASCT.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Francisco Diez-Fuertes, Maria Rosa Lopez-Huertas, Javier Garcia-Perez, Esther Calonge, Mercedes Bermejo, Elena Mateos, Pilar Marti, Nuria Muelas, Juan Jesus Vilchez, Mayte Coiras, Jose Alcami, Sara Rodriguez-Mora
Summary: LGMDD2 is a rare form of muscular dystrophy characterized by the addition of a 15-amino acid tail in the C-terminus of the TNPO3 gene. The study found that LGMDD2 patients exhibit a pro-inflammatory state, with alterations in IL-17 signaling pathway and increased activity of metallopeptidases and TNF response. Additionally, LGMDD2 patients have elevated levels of interferons and inflammatory mediators, suggesting an antiviral environment and resistance to HIV-1 infection, but potentially impairing muscular function and worsening disease progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Paula Martinez-Roman, Celia Crespo-Bermejo, Daniel Valle-Millares, Violeta Lara-Aguilar, Sonia Arca-Lafuente, Luz Martin-Carbonero, Pablo Ryan, Ignacio de los Santos, Maria Rosa Lopez-Huertas, Claudia Palladino, Maria Munoz-Munoz, Amanda Fernandez-Rodriguez, Mayte Coiras, Veronica Briz
Summary: This study found that the elimination of hepatitis C virus (HCV) using direct-acting antivirals (DAAs) did not modify the HIV reservoir and viral splicing. Additionally, individuals who spontaneously cleared HCV showed a significant decrease in the HIV reservoir, possibly due to an enhanced immune response.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Lorna Leal, Alberto C. Guardo, Luis M. Bedoya, Cristina Rodriguez de Miguel, Nuria Climent, Cristina Rovira, Manuela Beltran, Josep Llach, Jose Alcami, Angela D. M. Kashuba, Jose M. Gatell, Montserrat Plana, Felipe Garcia
Summary: Using colorectal tissue explants, we studied the impact of maraviroc (MVC), raltegravir (RAL), and ritonavir-boosted lopinavir (LPV/r) PEP-based regimens on rectal mucosal susceptibility to HIV-1 infection. We found that 28-day MVC treatment significantly suppressed viral replication and infectivity correlated with immune activation and senescence.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2023)
Article
Oncology
Sara Rodriguez-Mora, Lucia Perez-Lamas, Miriam Solera Sainero, Montserrat Torres, Clara Sanchez-Menendez, Magdalena Corona, Elena Mateos, Guiomar Casado-Fernandez, Jose Alcami, Javier Garcia-Perez, Mayte Perez-Olmeda, Maria Aranzazu Murciano-Anton, Javier Lopez-Jimenez, Valentin Garcia-Gutierrez, Mayte Coiras
Summary: Individuals with hematological diseases may not be fully protected from severe forms of COVID-19 after vaccination due to the disease or treatment they receive. A study found that individuals with hematological cancer who received a stem cell transplant showed reduced antibody levels in plasma, but those with autologous transplant had a similar cellular immune response to healthy donors, while those with allogeneic transplant had severely impaired cellular immune response. Transplantation did not affect the immune response against SARS-CoV-2 and most post-transplant infections were mild, indicating some level of immune protection.
Review
Pharmacology & Pharmacy
Andrea Rodriguez-Agustin, Victor Casanova, Judith Grau-Exposito, Sonsoles Sanchez-Palomino, Jose Alcami, Nuria Climent
Summary: Tyrosine kinase inhibitors (TKIs) are widely used to treat chronic myeloid leukemia (CML). Dasatinib, a broad-spectrum TKI with off-target effects, has immunomodulatory capabilities that enhance innate immune responses against cancerous and viral-infected cells. Studies have shown that dasatinib expands memory-like natural killer (NK) cells and γδ T cells, which are associated with improved control of CML and HIV infection. Additionally, dasatinib has potential as a senolytic drug by inducing apoptosis in senescent cells. This review examines the virological and immunogenetic factors associated with dasatinib's cytotoxic effects and discusses its therapeutic potential against CML, HIV infection, and aging.
Article
Pharmacology & Pharmacy
Alvaro Simba-Lahuasi, Jose Alcami, Manuela Beltran, Luis M. Bedoya, Jose Gallego
Summary: A virtual compound screening identified new chemical scaffolds that can block the interaction between HIV-1 and RRE-Rev. These compounds inhibit the complex formation by binding to the RRE and show antiretroviral activity.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sergi Chumillas, Saurabh Loharch, Manuela Beltran, Mateusz P. Szewczyk, Silvia Bernal, Maria C. Puertas, Javier Martinez-Picado, Jose Alcami, Luis M. Bedoya, Vicente Marchan, Jose Gallego
Summary: This study explored the optimization of the antiretroviral properties of benfluron and found that both the benzo[c] and cyclopentanone components are essential for its activity. The results provide insights for the design of new anti-HIV agents targeting the inhibition of Rev function.
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)