Editorial Material
Multidisciplinary Sciences
Douglas R. Wassarman, Philip J. Kranzusch
Summary: Cells utilize specialized nucleotide signals to activate defense mechanisms. A bacterial study has discovered a previously unknown class of signals formed by linking molecules of ATP and S-adenosyl methionine.
Editorial Material
Multidisciplinary Sciences
Urs Jenal
Summary: There are still many mysteries surrounding how antiviral responses affect a virus' ability to infect bacteria. The discovery that viruses can interfere with signalling mediated by second messengers provides insights into bacterial defences.
Editorial Material
Multidisciplinary Sciences
Mireille Farjo, Christopher B. Brooke
Summary: Influenza viruses infecting the same host can hinder each other's replication, leading to spatial structuring of infected cells in tissue and impacting viral evolution.
Editorial Material
Multidisciplinary Sciences
Richard Hodson
Summary: Researchers provide clear guidelines on what countries should do to prevent another disease outbreak with pandemic potential.
Editorial Material
Multidisciplinary Sciences
Simon Makin
Summary: The article discusses the precise adaptation of viruses to their hosts and the potential threats posed by mutations. Virologist Sara Sawyer shares a worrying discovery made in her laboratory regarding future threats.
News Item
Multidisciplinary Sciences
Miryam Naddaf
Summary: Genetic changes in avian influenza viruses have caused a global outbreak, spreading among numerous wild species.
News Item
Multidisciplinary Sciences
Philip Ball
Summary: Researchers around the world warn that easing restrictions during a surge in infections could lead to the emergence of new variants and pose risks to the health of unvaccinated individuals.
Article
Virology
Maite Freitas Silva Vaslin, Gustavo Peixoto Duarte da Silva, Alessandra Alevato Leal, Larissa Mayumi Bueno, Cintia Bittar, Gabriela Fabiano de Souza, Karine Lourenco, Maria Isabel Maldonado Coelho Guedes, Jose Luiz Proenca-Modena, Joao Pessoa Araujo Junior, Helena Lage Ferreira, Flavio Guimaraes da Fonseca
Summary: The Brazilian Society for Virology organized its annual national meeting in October 2022. After two consecutive online events, the 33rd meeting marked the return to in-person format. The meeting gathered undergraduate, graduate, and postdoc students, as well as international researchers, to discuss the latest virology research. Despite a slight decrease in attendance due to the associated costs, the meeting successfully achieved its goals of inspiring scientists and promoting high-quality research.
Article
Virology
Maite Freitas Silva Vaslin, Alessandra Alevato Leal, Larissa Mayumi Bueno, Cintia Bittar, Gabriela Fabiano de Souza, Karine Lourenco, Gustavo Peixoto Duarte da Silva, Maria Isabel Maldonado Coelho Guedes, Jose Luiz Proenca-Modena, Joao Pessoa Araujo Junior, Helena Lage Ferreira, Flavio Guimaraes da Fonseca
Summary: The Brazilian Society of Virology has successfully organized its 32nd annual meeting, yet again in an online format due to the challenges posed by the COVID-19 pandemic. The meeting attracted a large number of attendees, particularly undergraduate, graduate, and postdoc students, who had the opportunity to hear distinguished scientists from different countries present high-quality conferences and see young scientists showcase their latest research results. Despite the difficulties of another pandemic year, the 32nd SBV annual meeting achieved its primary goal of inspiring young scientists and facilitating discussions on high-quality virology research.
Review
Medicine, General & Internal
Anant Parasher
Summary: COVID-19, caused by the novel coronavirus SARS-CoV-2, has rapidly spread globally and presents in a spectrum of mild, moderate, and severe illness. Diagnosis is currently based on reverse-transcription PCR of nasopharyngeal and oropharyngeal swab samples, with treatment including ventilation, antipyretics, antivirals, antibiotics, and steroids.
POSTGRADUATE MEDICAL JOURNAL
(2021)
News Item
Multidisciplinary Sciences
Freda Kreier
Summary: Teeth from long-dead individuals and animals are providing insight into the history of modern pathogens.
Editorial Material
Multidisciplinary Sciences
Robert F. Garry
Summary: The Ebola virus can remain latent in human survivors for an extended period of time, as shown by a genomic comparison between the 2021 outbreak in Guinea and the West African outbreak that ended in 2016.
Editorial Material
Multidisciplinary Sciences
Caroline K. Martin, Margaret Kielian
Summary: Alphaviruses can be transmitted by mosquitoes to various species, including humans, potentially leading to fatal outcomes. The presence of conserved virus receptors between mosquitoes and humans could possibly explain the broad range of viral hosts.
Editorial Material
Multidisciplinary Sciences
Aris Katzourakis
Summary: This article highlights the dangers of overly optimistic assumptions on public health and urges policymakers to take immediate action in shaping the future.
News Item
Multidisciplinary Sciences
Saima May Sidik
Summary: A variant of H5N1 influenza that can spread between mammals may increase the risk of transmission.
Article
Multidisciplinary Sciences
Xiaojian Shi, Bryn Reinstadler, Hardik Shah, Tsz-Leung To, Katie Byrne, Luanna Summer, Sarah E. Calvo, Olga Goldberger, John G. Doench, Vamsi K. Mootha, Hongying Shen
Summary: A combinatorial genexgenexenvironment CRISPR screen targeting human SLC25 transporter family identified SLC25A39 as critical in mitochondrial glutathione import and its coordination with mitochondrial iron import to support OXPHOS. The study showed the high redundancy of the SLC25 carrier family and their transport activities coupled to metabolic state.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Stephen Tang, Vidyalakshmi Sethunath, Nebiyou Y. Metaferia, Marina F. Nogueira, Daniel S. Gallant, Emma R. Garner, Lauren A. Lairson, Christopher M. Penney, Jiao Li, Maya K. Gelbard, Sarah Abou Alaiwi, Ji-Heui Seo, Justin H. Hwang, Craig A. Strathdee, Sylvan C. Baca, Shatha AbuHammad, Xiaoyang Zhang, John G. Doench, William C. Hahn, David Y. Takeda, Matthew L. Freedman, Peter S. Choi, Srinivas R. Viswanathan
Summary: AR signaling in prostate cancer is driven by protein arginine methyltransferase 1 (PRMT1), which regulates AR recruitment and expression. Inhibition of PRMT1 impairs AR binding at specific sites and decreases expression of key oncogenes. Combined inhibition of AR and PRMT1 shows unique sensitivity in AR-driven prostate cancer cells.
Correction
Microbiology
Rui Guo, Yuchen Zhang, Mingxiang Teng, Chang Jiang, Molly Schineller, Bo Zhao, John G. Doench, Richard J. O'Reilly, Ethel Cesarman, Lisa Giulino-Roth, Benjamin E. Gewurz
NATURE MICROBIOLOGY
(2022)
Article
Oncology
Natalie B. Collins, Rose Al Abosy, Brian C. Miller, Kevin Bi, Qihong Zhao, Michael Quigley, Jeffrey J. Ishizuka, Kathleen B. Yates, Hans W. Pope, Robert T. Manguso, Yashaswi Shrestha, Marc Wadsworth, Travis Hughes, Alex K. Shalek, Jesse S. Boehm, William C. Hahn, John G. Doench, W. Nicholas Haining
Summary: This study found that activating mutations in the oncogene PI3K can enable tumor immune evasion by promoting an inhibitory myeloid microenvironment, leading to reduced effectiveness of immunotherapy. These findings are significant for improving the efficacy of immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Virology
Meagan E. Sullender, Linley R. Pierce, Mridula Annaswamy Srinivas, Stacey L. Crockett, Bria F. Dunlap, Rachel Rodgers, Lawrence A. Schriefer, Elizabeth A. Kennedy, Brittany M. Stewart, John G. Doench, Megan T. Baldridge, Robert C. Orchard
Summary: Viruses encode polyproteins to maximize their genetic capacity, which can be separated into individual components by viral proteases. Recent findings suggest that polyprotein processing can coordinate different phases of the viral life cycle. However, the molecular mechanisms of how host antiviral factors restrict norovirus infection are poorly understood.
JOURNAL OF VIROLOGY
(2022)
Article
Genetics & Heredity
Antoine Rebendenne, Priyanka Roy, Boris Bonaventure, Ana Luiza Chaves Valadao, Lowiese Desmarets, Mary Arnaud-Arnould, Yves Rouille, Marine Tauziet, Donatella Giovannini, Jawida Touhami, Yenarae Lee, Peter DeWeirdt, Mudra Hegde, Serge Urbach, Khadija El Koulali, Francisco Garcia de Gracia, Joe McKellar, Jean Dubuisson, Melanie Wencker, Sandrine Belouzard, Olivier Moncorge, John G. Doench, Caroline Goujon
Summary: Genome-wide CRISPR knockout and activation screens in Calu-3 lung cells and Caco-2 colorectal cells identify host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.
Article
Biochemistry & Molecular Biology
Nicholas Z. Lue, Emma M. Garcia, Kevin C. Ngan, Ceejay Lee, John G. Doench, Brian B. Liau
Summary: In this study, we use base editing and a DNA methylation reporter to scan mutations of DNMT3A in situ in cells. We identify mutations throughout the protein that disrupt function, including mutations at the interdomain interface that block allosteric activation. Surprisingly, we also find mutations in the PWWP domain that modulate enzyme activity by affecting DNA affinity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Oncology
Kimberly R. Hagel, Rand Arafeh, Sydney Gang, Taylor E. Arnoff, Rebecca C. Larson, John G. Doench, Nathan D. Mathewson, Kai W. Wucherpfennig, Marcela Maus, William C. Hahn
Summary: This study uncovers multiple antigen-dependent and independent mechanisms of CAR T-cell evasion by pancreatic cancer, including the loss of genes involved in GPI-anchor biosynthesis and attachment pathway and genes that regulate tumor transcriptional responses. The identification of these resistance mechanisms provides insights into the landscape of tumor cell intrinsic resistance and potential approaches to improve CAR T-cell therapy efficacy in pancreatic cancer.
Article
Multidisciplinary Sciences
Matteo Gentili, Bingxu Liu, Malvina Papanastasiou, Deborah Dele-Oni, Marc A. Schwartz, Rebecca J. Carlson, Aziz M. Al'Khafaji, Karsten Krug, Adam Brown, John G. Doench, Steven A. Carr, Nir Hacohen
Summary: In this study, genes regulating STING trafficking were systematically characterized, and their impact on STING-mediated responses was examined. The study revealed that the ESCRT complex promotes STING degradation and terminates STING signaling. Furthermore, a UBAP1 mutation was found to increase steady-state STING-dependent responses. Overall, this study uncovers the role of the ESCRT complex in regulating STING signaling.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Guoxun Wang, Di Zhang, Robert C. C. Orchard, Dustin C. C. Hancks, Tiffany A. A. Reese
Summary: This study identified a molecular mechanism of norovirus-induced cell death, which involves targeting mitochondria and inducing mitochondrial dysfunction. These findings provide insights into how noroviruses facilitate viral egress by inducing cell death and mitochondrial dysfunction.
Editorial Material
Cell Biology
Rajesh Gupta, Lisa A. Purcell, Davide Corti, Herbert W. Virgin
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Kathryn Gunn, Matti Myllykoski, John Z. Cao, Manna Ahmed, Bofu Huang, Betty Rouaisnel, Bill H. Diplass, Michael M. Levitt, Ryan Looper, John G. Doench, Keith L. Ligon, Harley I. Kornblum, Samuel K. McBrayers, Hai Yan, Cihangir Duy, Lucy A. Godley, Peppi Koivunen, Julie-Aurore Losman
Summary: Oncogenic mutations in IDH1 and IDH2 are commonly found in various cancers, including AML and glioma. The mutant IDH enzymes produce (R)-2HG, which is believed to promote cellular transformation by disrupting 2OG-dependent enzymes. This study reveals that (R)-2HG inhibits KDM5 histone lysine demethylases, contributing to cellular transformation in IDH-mutant AML and glioma.
Article
Oncology
Yoshinaga Ito, Deng Pan, Wubing Zhang, Xixi Zhang, Tiffany Y. Juan, Jason W. Pyrdol, Oleksandr Kyrysyuk, John G. Doench, X. Shirley Liu, Kai W. Wucherpfennig
Summary: Tumor heterogeneity is a major obstacle in cancer therapy, including immunotherapy. By targeting autophagy and TNF signaling pathways, MHC-I-deficient tumor cells can be sensitized to T cell-mediated apoptosis. Antigens from apoptotic MHC-I-deficient tumor cells can be efficiently cross-presented by dendritic cells, leading to increased infiltration of T cells producing IFN-γ and TNF-α. Targeting both pathways enables T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient cells.
Article
Medicine, Research & Experimental
Tianxia Li, Osamu Kikuchi, Jin Zhou, Yichen Wang, Babita Pokharel, Klavdija Bastl, Prafulla Gokhale, Aine Knott, Yanxi Zhang, John G. Doench, Zandra V. Ho, Daniel V. T. Catenacci, Adam J. Bass
Summary: Gastroesophageal adenocarcinomas (GEAs) frequently exhibit amplification of KRAS gene, resulting in overexpression of WT KRAS protein. This study investigates potential targets to enhance the efficacy of SHP2 inhibition in KRAS-amplified GEA, including those within the MAPK pathway and upstream RTKs. In vitro and in vivo experiments demonstrate that pan-ERBB kinase inhibition has potent cytotoxicity. Additionally, the combination of CDK4/6 inhibition with SHP2 inhibition shows greater efficacy in KRAS-amplified GEA compared to KRAS-mutant tumors. These findings suggest potential therapeutic combinations for clinical study in KRAS-amplified GEAs.
Review
Immunology
Hao Shi, John G. Doench, Hongbo Chi
Summary: CRISPR-based technologies offer a powerful platform for unbiased screening and functional genomics in various fields, including immunology. These technologies have uncovered previously unknown intracellular drivers and intercellular regulators in immune cells, and have expanded the readouts to the transcriptome for better mechanistic insights. CRISPR screens also allow for mapping of genetic interactions to identify genes that synergize or alleviate complex immune phenotypes.
NATURE REVIEWS IMMUNOLOGY
(2023)