Article
Medicine, Research & Experimental
Matthew Weichseldorfer, Yutaka Tagaya, Marvin Reitz, Anthony L. DeVico, Olga S. Latinovic
Summary: This study aims to understand the different conformations of CCR5 involved in HIV entry and identify the specific CCR5 populations that are best targeted to inhibit HIV-1 entry. Through quantification and visualization, it was found that a decreased surface presence of certain CCR5 subpopulations after infection represents a highly relevant target for future antiviral therapy strategies. The findings will contribute to the development of inhibitors to block CCR5 usage by HIV-1 and inform future HIV-1 vaccine design.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Vilim Molnar, Vid Matisic, Ivan Kodvanj, Roko Bjelica, Zeljko Jelec, Damir Hudetz, Eduard Rod, Fabijan Cukelj, Trpimir Vrdoljak, Dinko Vidovic, Mario Staresinic, Srecko Sabalic, Borut Dobricic, Tadija Petrovic, Darko Anticevic, Igor Boric, Rok Kosir, Ursula Prosenc Zmrzljak, Dragan Primorac
Summary: Osteoarthritis is a common cause of disability worldwide, affecting all joint tissues equally. The pathogenesis involves low-grade inflammation leading to an imbalance between anabolic and catabolic processes. The complex network of cytokines regulating these processes plays a central role in the development and progression of osteoarthritis, with concentrations of proinflammatory and anti-inflammatory cytokines varying based on disease stage and activity levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Lida Mo, Guosheng Su, Hanzhen Su, Wanhong Huang, Xiaolu Luo, Chuanmin Tao
Summary: This study aimed to investigate the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM). The study found that IL-10 was positively correlated with other inflammatory indicators in both blood and cerebrospinal fluid, suggesting its involvement in both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Virology
Biao Zhang, Jin-Biao Liu, Lina Zhou, Xu Wang, Shazheb Khan, Wen-Hui Hu, Wen-Zhe Ho
Summary: Activation of cytosolic DNA sensors inhibits HIV infection and replication in macrophages by inducing the production of interferons and other antiviral factors.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ramesh Kumar, Madhav Bhatia, Kalpana Pai
Summary: Visceral leishmaniasis is caused by the protozoan parasite Leishmania donovani, characterized by the host's inability to generate an effective immune response. Different types of macrophages play important roles in the disease progression, and chemokines and chemokine receptors are crucial in the pathogenesis.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Bjoern-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Luebke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Galvez, Christiane Mummert, Caroline Passaes, Johanna M. M. Eberhard, Carsten Muenk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gabor A. Dunay, Florian Klein, Dieter Haeussinger, Johannes C. C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Saez-Cirion, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado, Guido Kobbe
Summary: A 53-year-old male who received CCR5 Delta 32/Delta 32 hematopoietic stem cell transplantation for acute myeloid leukemia showed long-term remission of HIV-1. Despite sporadic traces of HIV-1 DNA, replication-competent virus was not detected in ex vivo and in vivo assays. Low levels of immune activation and declining HIV-1-specific immune responses indicated a lack of ongoing antigen production. After 4 years of treatment interruption, the absence of viral rebound and immunological correlates provide strong evidence for HIV-1 cure after CCR5 Delta 32/Delta 32 HSCT.
Review
Immunology
Mojgan Noroozi Karimabad, Gholamhossein Hassanshahi, Nicholas G. Kounis, Virginia Mplani, Pavlos Roditis, Christos Gogos, Maria Lagadinou, Stelios F. Assimakopoulos, Periklis Dousdampanis, Ioanna Koniari
Summary: COVID-19 is a progressive viral pandemic associated with immunological mechanisms. The CC and CXC chemokines play a role in COVID-19 and may reflect the development of reasonable strategies for COVID-19 management.
Article
Oncology
Mohd Mughees, Jyoti Bala Kaushal, Gunjan Sharma, Saima Wajid, Surinder Kumar Batra, Jawed Akhtar Siddiqui
Summary: Chemokines play a crucial role in tumorigenesis and cancer progression, particularly in prostate cancer. Inflammatory processes and the secretion of chemokines and cytokines in the tumor microenvironment play a key role in cancer development and treatment resistance.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Cell Biology
Anca Filimon, Iulia A. Preda, Adina F. Boloca, Gabriela Negroiu
Summary: Cutaneous melanoma, accounting for a small percentage of skin cancers but causing the majority of deaths, has unique mutations and capabilities to evade immune control. Interleukin-8 (IL-8) plays a significant role in advanced melanomas and operates in orchestrated programs within signaling webs. Understanding the molecular mechanisms of IL-8's impact on immune cells is crucial for changing the fate of tumors. Further scientific exploration of IL-8's targets in the therapeutic management of melanoma is of great importance.
Article
Medicine, General & Internal
Manukumar Honnayakanahalli Marichannegowda, Michelle Zemil, Lindsay Wieczorek, Eric Sanders-Buell, Meera Bose, Anne Marie O'Sullivan, David King, Leilani Francisco, Felisa Diaz-Mendez, Saini Setua, Nicolas Chomont, Nittaya Phanuphak, Jintanat Ananworanich, Denise Hsu, Sandhya Vasan, Nelson L. Michael, Leigh Anne Eller, Sodsai Tovanabutra, Yutaka Tagaya, Merlin L. Robb, Victoria R. Polonis, Hongshuo Song
Summary: The earliest X4 viruses evolved de novo from the transmitted/founder (T/F) strains, and strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive the X4 variants to replicate mainly in the central memory (CM) and naive CD4 subsets. The origin of the X4 viruses preceded accelerated CD4 decline. All except one X4 virus identified in the current study lost the conserved V3 N301 glycan site.
Review
Microbiology
Erin P. Madeen, Frank Maldarelli, John D. Groopman
Summary: The transmission risk of HIV depends on the infectivity of the HIV+ partner and personal susceptibility factors of the HIV- partner. Aflatoxin B1 (AFB(1)) exposure correlates with HIV viral load, leading to inflammation in mucosal tissues and increased susceptibility to HIV infection. Geographically, AFB(1) exposure and HIV sexual transmission hotspots overlap in many low-income countries, suggesting a potential link between dietary toxins and increased risk of HIV transmission.
Review
Genetics & Heredity
Carlo Giacomo Leo, Pierpaolo Mincarone, Maria Rosaria Tumolo, Alessandra Panico, Marcello Guido, Antonella Zizza, Roberto Guarino, Giuseppe De Santis, Raffaella Sedile, Saverio Sabina
Summary: miRNAs play crucial roles in gene expression regulation and dysregulation can lead to human diseases. This study systematically analyzed scientific literature to identify miRNAs associated with HIV, highlighting hsa-miR-29 family, hsa-miR-146b-5p, and hsa-miR-150-5p as frequently reported miRNAs.
Article
Immunology
Rebekka F. Thudium, Hedda Ringheim, Andreas Ronit, Hedda Hoel, Thomas Benfield, Amanda Mocroft, Jan Gerstoft, Marius Troseid, Alvaro H. Borges, Sisse R. Ostrowski, Jorgen Vestbo, Susanne D. Nielsen
Summary: The study found that two markers of systemic inflammation, TNF alpha and IL-1 beta, were independently associated with emphysema in PLWH, potentially contributing to the pathogenesis of emphysema. The effect of IL-1 beta on emphysema appears to be mediated through pathways independent of excessive smoking.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Dermatology
Zhongshuai Wang, Huijuan Zhao, Wanying Zhai, Xiaofeng Zhang, Li Li, Chen Yuan, Yi Li, Yangqun Li, Yan Yan, Baoxi Wang
Summary: Mutations in the gamma-secretase complex have been well-described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60%-70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. This study investigated the involvement of epigenetic modifications in sporadic HS and found downregulation of CXCL16 and CXCR6 in HS.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Immunology
Seth H. Pincus, Ryan B. Craig, Lauren Weachter, Celia C. LaBranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, David C. Montefiori, Pamela A. Kozlowski
Summary: Research has shown that bispecific immunoadhesins binding to HIV envelope glycoproteins exhibit potent neutralization activity and deliver cytotoxic effects.
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
Developmental Biology
Elena Melendez, Dafni Chondronasiou, Lluc Mosteiro, Jaime Martinez de Villarreal, Marcos Fernandez-Alfara, Cian J. Lynch, Dirk Grimm, Francisco X. Real, Jose Alcami, Nuria Climent, Federico Pietrocola, Manuel Serrano
Summary: The presence of natural killer (NK) cells significantly hampers the reprogramming of cells, both in vitro and in vivo. NK cells recognize and kill partially reprogrammed cells, leading to a decrease in in vivo reprogramming. Depletion of NK cells increases the efficiency of in vivo reprogramming.
Article
Microbiology
Mingyu Han, Vincent Cantaloube-Ferrieu, Maorong Xie, Marie Armani-Tourret, Marie R. Woottum, Jean-Christophe Pages, Philippe R. Colin, Bernard Lagane, Serge R. Benichou
Summary: The study shows that HIV-1 can effectively infect macrophages through cell-to-cell transfer, even with virus isolates initially defined as non-macrophage tropic in cell-free infection. This intercellular viral transfer is facilitated by enhanced interactions between the HIV-1 envelope glycoproteins and cellular entry receptors.
Article
Immunology
Jenifer Masip, Norma Rallon, Elena Yeregui, Montserrat Olona, Salvador Resino, Jose M. Benito, Consuelo Vilades, Graciano Garcia-Pardo, Jose Alcami, Ezequiel Ruiz-Mateos, Frederic Gomez-Bertomeu, Montserrat Vargas, Marta Navarro, Jose A. Oteo, Juan A. Pineda, Anna Marti, Veronica Alba, Francesc Vidal, Joaquin Peraire, Anna Rull
Summary: Long-term elite controllers exhibit elevated tricarboxylic acid (TCA) cycle function and alpha-ketoglutaric acid is identified as a key metabolite in persistent control. Conversely, lipidomics analysis suggests that an elevated lipidomics plasma profile could predict the reignition of viral replication in LTEC individuals.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Multidisciplinary Sciences
Carolina Herrera, Mackenzie L. Cottrell, John Prybylski, Angela D. M. Kashuba, Ronald S. Veazey, Javier Garcia-Perez, Natalia Olejniczak, Clare F. McCoy, Paul Ziprin, Nicola Richardson-Harman, Jose Alcami, Karl R. Malcolm, Robin J. Shattock
Summary: The utility of non-human primates in evaluating antiretroviral drugs for HIV treatment and prevention is questionable due to pharmacological differences between humans and macaques. We developed an ex vivo model using tissue explants to identify differences in drug efficacy between the two species. Our results showed that high concentrations of tenofovir and maraviroc predicted anti-viral efficacy, with greater inhibitory potency observed in macaques compared to humans.
Article
Immunology
Tomas M. Grosso, Jose Alcami, Jose R. Arribas, Marta Martin, Irini Sereti, Philip Tarr, Pedro Cahn, Bonaventura Clotet, Omar Sued, Eugenia Negredo
Summary: Aging is a significant research topic as the average age of the population increases. Factors such as epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive cell senescence and promote tissue inflammation. Individuals living with HIV are more susceptible to accelerated aging, and inflammation biomarkers can be helpful for prognosis and treatment strategies.
Article
Biology
Fanny Momboisse, Giacomo Nardi, Philippe Colin, Melanie Hery, Nelia Cordeiro, Simon Blachier, Olivier Schwartz, Fernando Arenzana-Seisdedos, Nathalie Sauvonnet, Jean-Christophe Olivio-Marin, Bernard Lagane, Thibault Lagache, Anne Brelot
Summary: This study investigated the impact of different states on the biological function and therapeutic targeting of CC chemokine receptor 5 (CCR5). The researchers used microscopy and statistical methods to track and classify the motion of different receptor subpopulations. The results showed that CCR5 exists in various ligand-free forms, stabilized by different ligands. Agonist stimulation restricted the mobility of CCR5 and led to its clustering, while inverse agonist stimulation had the opposite effect. The study also demonstrated the importance of CCR5 dimerization in its coupling to G proteins, immobilization and clustering upon activation, and receptor endocytosis.
Review
Immunology
Erick De La Torre-tarazona, Ruben Ayala-Suarez, Francisco Diez-Fuertes, Jose Alcami
Summary: This article reviews the main discoveries achieved by transcriptomic approaches on HIV controller (HIC) and long-term non-progressor (LTNP) individuals. Different studies using high throughput techniques have elucidated multifactorial causes implied in natural control of HIV infection. Genes related to IFN response, calcium metabolism, ribosome biogenesis, among others, are commonly differentially expressed in LTNP/HIC individuals. Additionally, pathways related with activation, survival, proliferation, apoptosis and inflammation, can be deregulated in these individuals. Likewise, recent transcriptomic studies include high-throughput sequencing in specific immune cell subpopulations, finding additional gene expression patterns associated to viral control and/or non-progression in immune cell subsets.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhicheng Zhou, Isabelle Staropoli, Anne Brelot, Peggy Suzanne, Aurelien Lesnard, Fanny Fontaine, Serge Perato, Sylvain Rault, Olivier Helynck, Fernando Arenzana-Seisdedos, Jana Sopkova-de Oliveira Santos, Bernard Lagane, Helene Munier-Lehmann, Philippe Colin
Summary: In this study, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These bis-imidazoline compounds showed potent displacement of CXCL12 binding and inhibition of CXCL12-mediated chemotaxis and HIV-1 infection. Further studies revealed that the alkyl chain length of these compounds influenced their properties and functions on CXCR4. These findings may contribute to the design of specific CXCR4 antagonists targeting different functions of the receptor.
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
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
Microbiology
Rajesh P. Ringe, Philippe Colin, Gabriel Ozorowski, Joel D. Allen, Anila Yasmeen, Gemma E. Seabright, Jeong Hyun Lee, Aleksandar Antanasijevic, Kimmo Rantalainen, Thomas Ketas, John P. Moore, Andrew B. Ward, Max Crispin, P. J. Klasse
Summary: The study reveals that the neutralizing antibodies against HIV-1 have different effects on different fusion peptide epitopes, which are associated with persistent fractions. By conducting pseudovirus depletion experiments and analyzing the structure of soluble trimers, it is found that glycosylation variation may be the cause of the differences in binding and neutralization effects.