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)
Review
Immunology
Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: Immune checkpoint inhibitors have revolutionized immuno-oncology by achieving durable immune control of cancer, however, tumor immune evasion mechanisms pose a challenge for treatment development. Combination therapies targeting NK cell-activating receptors like NKG2D are emerging as frontrunners in immuno-oncology, with strategies to boost MICA/B expression and inhibit their shedding being proposed for enhancing antitumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Lesley R. de Armas, Christina Gavegnano, Suresh Pallikkuth, Stefano Rinaldi, Li Pan, Emilie Battivelli, Eric Verdin, Ramzi T. Younis, Rajendra Pahwa, Sion L. Williams, Raymond F. Schinazi, Savita Pahwa
Summary: The study used the dual reporter virus HIVGKO to investigate latency establishment and maintenance in CD4(+) T cells, and analyzed latently infected cells using single cell technologies. The research found that JAK1/2 inhibitors could reduce HIV infection events and block HIV reactivation from latent cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Article
Biochemistry & Molecular Biology
Daniela A. Covino, Maria G. Desimio, Margherita Doria
Summary: This study explores the potential strategies for clearing latent HIV reservoirs by using combinations of different latency-reversing agents (LRAs), with a focus on investigating the possibility of enhancing NK cell-mediated viral suppression through 2-LRA combinations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Florencia Secchiari, Sol Yanel Nunez, Jessica Mariel Sierra, Andrea Ziblat, Maria Victoria Regge, Ximena Lucia Raffo Iraolagoitia, Agustin Rovegno, Carlos Ameri, Fernando Pablo Secin, Nicolas Richards, Hernando Rios Pita, Gonzalo Vitagliano, Luis Rico, Mauro Mieggi, Florencia Frascheri, Nicolas Bonanno, Leandro Blas, Aldana Trotta, Adrian David Friedrich, Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: NKG2D is an important activating receptor of natural killer (NK) cells that recognizes multiple ligands, including MICA. This study found that MICA is overexpressed in renal cell carcinoma (RCC) and is associated with decreased overall survival in RCC patients. Both tumor cells and tumor-infiltrating leukocytes showed increased MICA expression, while peripheral blood NK cells exhibited downregulated NKG2D. Furthermore, these NKG2D-expressing tumor-infiltrating NK cells displayed functional impairment and altered metabolic fitness.
Article
Microbiology
Ariane Zutz, Lin Chen, Franziska Sippl, Andreas Humpe, Christian Schoelz
Summary: The study focused on screening latent reservoirs in HIV-1 infected individuals and identified two novel compounds with high reactivation efficiency and low toxicity as potential new treatment options for reversing latency.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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)
Review
Medicine, Research & Experimental
Kerry A. Whalen, Kavya Rakhra, Naveen K. Mehta, Alexander Steinle, Jennifer S. Michaelson, Patrick A. Baeuerle
Summary: The field of immuno-oncology has revolutionized cancer patient care, but there are still challenges with current therapeutic approaches targeting T cells. Engaging the innate immune system, especially natural killer (NK) cells, has emerged as a promising modality in immunotherapy. This review focuses on therapeutic strategies that selectively engage NK cells for cancer therapy, particularly targeting the activating receptors NKG2D and CD16A.
Review
Biochemistry & Molecular Biology
Annika P. Schnell, Stephan Kohrt, Andrea K. Thoma-Kress
Summary: HTLV-1, a retrovirus infecting CD4(+) T-cells and causing ATLL, evades efficient CTL responses by repressing viral gene expression. Therapeutic strategies aim to transiently activate viral gene expression and antigen presentation to enhance CTL responses and expose the latent HTLV-1 reservoir. LRAs like HDACi and P-TEFb activators, studied in the context of HIV, may also be effective against HTLV-1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Cristina Ceriani, Gabrielle S. Streeter, Kena J. Lemu, Katherine S. James, Simon Ghofrani, Brigitte Allard, Bonnie E. Shook-Sa, David M. Margolis, Nancie M. Archin
Summary: The study evaluated the stability of reference genes (RGs) after latency-reversing agent (LRA) exposure and found that TBP, UBE2D2, and RPL27A were the most stable RGs, while GAPDH showed the most variability. Using unstable RGs significantly impacted the accuracy of host gene and HIV gene expression data.
JOURNAL OF VIROLOGY
(2021)
Review
Cell Biology
Sushant Khanal, Madison Schank, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao
Summary: Eradication of latent HIV infection is a global health challenge, with popular strategies for HIV cure involving reactivation and killing of virus-infected cells. While antiretroviral therapy can halt HIV replication, it cannot completely eliminate latent proviruses, leading to reservoirs of infection that can cause cellular and systemic complications in HIV patients despite lack of active viral production. Studies into the mechanisms of HIV latency and reservoir formation are crucial for identifying strategies to eliminate viral reservoirs and ultimately cure HIV infection.
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Article
Virology
Terry L. Hafer, Abby Felton, Yennifer Delgado, Harini Srinivasan, Michael Emerman
Summary: This study aimed to investigate whether host factors required for HIV-1 replication also play a role in latency reversal. By using a CRISPR gene library and analyzing RNA sequencing data, several key HIV-1 dependency factors were identified, with CCNT1 being the most crucial factor for latency reactivation.
Article
Immunology
Joana Furtado Milao, Luca Love, George Gourgi, Lukas Derhaschnig, J. Peter Svensson, Anders Soennerborg, Robert van Domselaar
Summary: The establishment of a latency reservoir poses a significant challenge in curing HIV-1. The shock-and-kill strategy, which aims to reactivate latent HIV-1, has not been successful with current latency reversal agents (LRAs). However, this study suggests that NK cells stimulated with a caspase inhibitor can induce latency reversal in co-cultures with HIV-1 latently infected cells. The researchers also identified a secreted factor by NK cells that is responsible for HIV-1 reactivation, indicating the potential of this approach in reducing viral latency reservoirs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Loredana Cifaldi, Margherita Doria, Nicola Cotugno, Sonia Zicari, Caterina Cancrini, Paolo Palma, Paolo Rossi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Maria G. Desimio, Daniela A. Covino, Margherita Doria
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Microbiology
Eleonora Cimini, Alessandra Sacchi, Sara De Minicis, Veronica Bordoni, Rita Casetti, Germana Grassi, Francesca Colavita, Concetta Castilletti, Maria Rosaria Capobianchi, Giuseppe Ippolito, Maria Giovanna Desimio, Margherita Doria, Chiara Agrati
Article
Cell Biology
Cristina Cifaldi, Nicola Cotugno, Silvia Di Cesare, Silvia Giliani, Gigliola Di Matteo, Donato Amodio, Eva Piano Mortari, Maria Chiriaco, Danilo Buonsenso, Paola Zangari, Daria Pagliara, Stefania Gaspari, Rita Carsetti, Paolo Palma, Andrea Finocchi, Franco Locatelli, Paolo Rossi, Margherita Doria, Caterina Cancrini
JOURNAL OF LEUKOCYTE BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Cristina Bertulli, Antonio Marzollo, Margherita Doria, Silvia Di Cesare, Claudio La Scola, Francesca Mencarelli, Andrea Pasini, Maria Carmen Affinita, Enrico Vidal, Pamela Magini, Paola Dimartino, Riccardo Masetti, Laura Greco, Patrizia Palomba, Francesca Conti, Andrea Pession
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Maria Giovanna Desimio, Eleonora Cesari, Maria Sorrenti, Massimo De Felici, Donatella Farini
Summary: STRA8, as a key gene in germ cells, interacts with itself and other transcription factors, playing a negative role in Ebox-mediated transcriptional activity. It was found that STRA8 interacts with different transcription factors, in addition to its known role as an 'amplifier' of the meiotic program, to finely modulate the balance between germ cell proliferation, differentiation and acquisition of meiotic competence.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Editorial Material
Medicine, General & Internal
Margherita Doria
Article
Immunology
Maria Giovanna Desimio, Andrea Finocchi, Gigliola Di Matteo, Silvia Di Cesare, Carmela Giancotta, Francesca Conti, Luciana Chessa, Maria Piane, Davide Montin, Marta Dellepiane, Paolo Rossi, Caterina Cancrini, Margherita Doria
Summary: NK cells in A-T patients show reduced NKG2D expression, possibly contributing to increased susceptibility. The abnormal expression of NKG2D in A-T patients may be associated with disease progression.
CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daniela A. Covino, Maria G. Desimio, Margherita Doria
Summary: This study explores the potential strategies for clearing latent HIV reservoirs by using combinations of different latency-reversing agents (LRAs), with a focus on investigating the possibility of enhancing NK cell-mediated viral suppression through 2-LRA combinations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Loredana Frassinelli, Elisa Orecchini, Sofian Al-Wardat, Marco Tripodi, Carmine Mancone, Margherita Doria, Silvia Galardi, Silvia Anna Ciafre, Alessandro Michienzi
Summary: ADAR2 acts as a suppressor of L1 retrotransposition by inhibiting its activity, forming a complex with multiple non-ribosomal ADAR2-interacting factors.
Article
Immunology
Margherita Doria, Sonia Zicari, Nicola Cotugno, Sara Dominguez-Rodriguez, Alessandra Ruggiero, Giuseppe R. Pascucci, Alfredo Tagarro, Pablo Rojo Conejo, Eleni Nastouli, Kathleen Gartner, Mark Cameron, Brian Richardson, Caroline Foster, Sion L. Williams, Stefano Rinaldi, Anita De Rossi, Carlo Giaquinto, Paolo Rossi, Savita Pahwa, Paolo Palma
Summary: The study found that initiating ART early in infancy can protect the NK cell compartment and reduce the risk of HIV-1 reservoir. Compared to late treated patients, early treated patients showed better NK cell function and lower HIV-1 reservoir.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2021)
Article
Pediatrics
Beatrice Rivalta, Donato Amodio, Cinzia Milito, Maria Chiriaco, Silvia Di Cesare, Carmela Giancotta, Francesca Conti, Veronica Santilli, Lucia Pacillo, Cristina Cifaldi, Maria Giovanna Desimio, Margherita Doria, Isabella Quinti, Rita De Vito, Gigliola Di Matteo, Andrea Finocchi, Paolo Palma, Antonino Trizzino, Alberto Tommasini, Caterina Cancrini
Summary: Activated PI3K-kinase Delta Syndrome (APDS) is an autosomal-dominant primary immunodeficiency caused by constitutive activation of the PI3K delta kinase. Patients show impaired immune function, including lymphopenia, hypogammaglobulinemia, and inflammation. Treatments include targeted pharmacologic inhibitors and HSCT.
FRONTIERS IN PEDIATRICS
(2021)
Article
Oncology
Carla Proserpio, Silvia Galardi, Maria Giovanna Desimio, Alessandro Michienzi, Margherita Doria, Antonella Minutolo, Claudia Matteucci, Silvia Anna Ciafre
Summary: The involvement of the MEOX2 transcription factor in glioblastoma stem cells (GSCs) reveals a novel function in the regulation of GSC metabolism, which is crucial for their survival and growth. These findings provide new insights into the molecular mechanisms of GSCs and potential targets for anti-cancer therapies.
Article
Multidisciplinary Sciences
Erica Giuliani, Maria Giovanna Desimio, Margherita Doria
SCIENTIFIC REPORTS
(2019)
Article
Virology
Naiqing Xu, Xinen Tang, Xin Wang, Miao Cai, Xiaowen Liu, Xiaolong Lu, Shunlin Hu, Min Gu, Jiao Hu, Ruyi Gao, Kaituo Liu, Yu Chen, Xiufan Liu, Xiaoquan Wang
Summary: This study found that the H9N2 subtype avian influenza virus has a high airborne transmissibility, while the H7N9 virus does not. The Hemagglutinin protein of the H9N2 virus was found to play a key role in replication, stability, and airborne transmission.
Article
Virology
Samar S. Ewies, Sabry M. Tamam, Ahmed S. Abdel-Moneim, Sherin R. Rouby
Summary: Contagious ecthyma (CE) is a highly contagious viral disease of sheep and goats worldwide. The study provided a clinical description of CE and screened for genetic variation in the B2L gene. Infected sheep exhibited anorexia and oral lesions, while inoculated chicken embryos showed pock lesions. The B2L gene was successfully amplified and found to be highly conserved.
Article
Virology
Yigal Farnoushi, Dan Heller, Avishai Lublin
Summary: In recent years, new variants of avian reovirus (ARV) have caused a variety of symptoms in chickens worldwide, including viral arthritis/tenosynovitis. This study analyzed emerging ARV variants in Israel and found significant genetic diversity. Most ARV isolates in Israel belonged to genotypic cluster 5 (GC5). The study suggests that Israel has not experienced the emergence of new ARV variants since the introduction of the live vaccine (ISR-7585), but ongoing monitoring is needed due to the continuous emergence of ARV variants.
Article
Virology
Shigeru Tajima, Michiyo Kataoka, Yuki Takamatsu, Hideki Ebihara, Chang-Kweng Lim
Summary: Yokose virus (YOKV), a bat-associated flavivirus, was found to replicate at a slower rate in mosquito cells compared to other mosquito-borne flaviviruses. Specific nucleotide mutations in the virus were identified to enhance its proliferation ability in mosquito cells.
Article
Virology
Alejandra Borjabad, Baojun Dong, Wei Chao, David J. Volsky, Mary Jane Potash
Summary: This study investigated HIV brain disease using a mouse model, and found that poly I:C can reverse associated cognitive impairment and reduce virus burden. The results also revealed transcriptional changes related to neuronal function and innate immune responses.
Article
Virology
Ching-Hung Lin, Feng-Cheng Hsieh, Meilin Wang, Chieh Hsu, Hsuan-Wei Hsu, Chun-Chun Yang, Cheng-Yao Yang, Hung-Yi Wu
Summary: This study demonstrates that the synthesis of coronavirus subgenomic mRNA is not solely determined by the sequence homology between the leader TRS and TRS-B, but also by the disassociation of the coronavirus polymerase from the viral genome. This finding provides a new insight into the transcription mechanism of coronaviruses.
Article
Virology
Nicholas S. Kron, Benjamin W. Neuman, Sathish Kumar, Patricia L. Blackwelder, Dayana Vidal, Delphina Z. Walker-Phelan, Patrick D. I. Gibbs, Lynne A. Fieber, Michael C. Schmale
Summary: Two recent studies documented the genome of a novel virus in marine animals, finding that the virus is widespread in apparently healthy animals but not highly expressed in neurons. The studies also identified viral replication factories and high levels of defective genomes in chronically infected animals.
Article
Virology
Andrew M. Ramey, Laura C. Scott, Christina A. Ahlstrom, Evan J. Buck, Alison R. Williams, Mia Kim Torchetti, David E. Stallknecht, Rebecca L. Poulson
Summary: We successfully detected and characterized highly pathogenic avian influenza viruses in hunter-harvested wild waterfowl samples from western Alaska. Genomic analysis revealed three independent viral introductions into Alaska. Our findings demonstrate the utility and potential limitations of using molecular processing approaches directly on original swab samples for viral research and monitoring.
Article
Virology
Ting Gong, Dongdong Wu, Yongzhi Feng, Xing Liu, Qi Gao, Xiaoyu Zheng, Zebu Song, Heng Wang, Guihong Zhang, Lang Gong
Summary: This study discovered that quercetin can inhibit PEDV replication both in vivo and in vitro, and alleviate the clinical symptoms and intestinal injury caused by the virus. This provides a new direction for the development of PED antiviral drugs.
Article
Virology
Min Zhu, Hao Zeng, Jianqiao He, Yaohui Zhu, Pingping Wang, Jianing Guo, Jinfan Guo, Huabo Zhou, Yifeng Qin, Kang Ouyang, Zuzhang Wei, Weijian Huang, Ying Chen
Summary: The reassortment between avian H9N2 and Eurasian avian-like (EA) H1N1 viruses may have potentially changed from avian-to-mammals adaptation. This study found that the introduction of EA H1N1 internal genes into H9N2 virus restored the replication capability and resulted in extreme virulence in some cases. This raises new concerns for public health due to the possible coexistence of H9N2 and EA H1N1 viruses in dogs.