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Journal PLoS Pathog

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Enveloped RNA virus utilization of phosphatidylserine receptors: Advantages of exploiting a conserved, widely available mechanism of entry.

Dana Bohan, Wendy Maury,

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009899]

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The viral nucleocapsid protein and the human RNA-binding protein Mex3A promote translation of the Andes orthohantavirus small mRNA.

Jorge Vera-Otarola, Estefania Castillo-Vargas, Jenniffer Angulo, Francisco M Barriga, Eduard Batlle, Marcelo Lopez-Lastra,

The capped Small segment mRNA (SmRNA) of the Andes orthohantavirus (ANDV) lacks a poly(A) tail. In this study, we characterize the mechanism driving ANDV-SmRNA translation. Results show that the ANDV-nucleocapsid protein (ANDV-N) promotes in vitro translation from capped mRNAs without replacing eukaryotic initiation factor (eIF) 4G. Using an RNA affinity ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009931]

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Research with variola virus after smallpox eradication: Development of a mouse model for variola virus infection.

Bernard Moss, Geoffrey L Smith,

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009911]

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The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.

Charlotte Vandermeulen, Tina O'Grady, Jerome Wayet, Bartimee Galvan, Sibusiso Maseko, Majid Cherkaoui, Alice Desbuleux, Georges Coppin, Julien Olivet, Lamya Ben Ameur, Keisuke Kataoka, Seishi Ogawa, Olivier Hermine, Ambroise Marcais, Marc Thiry, Franck Mortreux, Michael A Calderwood, Johan Van Weyenbergh, Jean-Marie Peloponese, Benoit Charloteaux, Anne Van den Broeke, David E Hill, Marc Vidal, Franck Dequiedt, Jean-Claude Twizere,

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009919]

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Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes.

Courtney E McDougal, Zachary T Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M Stevenson, Daniel Amador-Noguez, Mark J Miller, John-Demian Sauer,

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009493]

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A 3,000-year-old, basal S. enterica lineage from Bronze Age Xinjiang suggests spread along the Proto-Silk Road.

Xiyan Wu, Chao Ning, Felix M Key, Aida Andrades Valtueña, Aditya Kumar Lankapalli, Shizhu Gao, Xuan Yang, Fan Zhang, Linlin Liu, Zhongzhi Nie, Jian Ma, Johannes Krause, Alexander Herbig, Yinqiu Cui,

Salmonella enterica (S. enterica) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S. enterica. ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009886]

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Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.

Saray Gutiérrez, Julia Fischer, Raja Ganesan, Nina Judith Hos, Gökhan Cildir, Martina Wolke, Alberto Pessia, Peter Frommolt, Vincenzo Desiderio, Vidya Velagapudi, Nirmal Robinson,

Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009943]

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Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.

Johanna West, Juliane Röder, Tatyana Matrosovich, Jana Beicht, Jan Baumann, Nancy Mounogou Kouassi, Jennifer Doedt, Nicolai Bovin, Gianpiero Zamperin, Michele Gastaldelli, Annalisa Salviato, Francesco Bonfante, Sergei Kosakovsky Pond, Sander Herfst, Ron Fouchier, Jochen Wilhelm, Hans-Dieter Klenk, Mikhail Matrosovich,

The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino acids in the corresponding positions of HA. The precursor ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009566]

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Immunological exhaustion: How to make a disparate concept operational?

Hannah Kaminski, Maël Lemoine, Thomas Pradeu,

In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009892]

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Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.

Mingzhu Ding, Jinfeng Wu, Rui Sun, Lijun Yan, Lei Bai, Jiajian Shi, Hua Feng, Yuqi Zhang, Ke Lan, Xing Wang,

Kaposi's sarcoma-associated herpesvirus (KSHV) preferentially infects and causes Kaposi's sarcoma (KS) in male patients. However, the biological mechanisms are largely unknown. This study was novel in confirming the extensive nuclear distribution of the androgen receptor (AR) and its co-localization with viral oncoprotein of latency-associated nuclear antigen in KS lesions, indicating ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009947]

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The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection.

Jinlin Li, Noemi Nagy, Jiangnan Liu, Soham Gupta, Teresa Frisan, Thomas Hennig, Donald P Cameron, Laura Baranello, Maria G Masucci,

Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009954]

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Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species.

Josie F Gibson, Grace R Pidwill, Oliver T Carnell, Bas G J Surewaard, Daria Shamarina, Joshua A F Sutton, Charlotte Jeffery, Aurélie Derré-Bobillot, Cristel Archambaud, Matthew K Siggins, Eric J G Pollitt, Simon A Johnston, Pascale Serror, Shiranee Sriskandan, Stephen A Renshaw, Simon J Foster,

Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S. aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009880]

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Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice.

Aurore Demars, Armelle Vitali, Audrey Comein, Elodie Carlier, Abdulkader Azouz, Stanislas Goriely, Justine Smout, Véronique Flamand, Mégane Van Gysel, Johan Wouters, Jan Abendroth, Thomas E Edwards, Arnaud Machelart, Eik Hoffmann, Priscille Brodin, Xavier De Bolle, Eric Muraille,

Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009887]

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PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection.

Zhenyu Wang, Jing Chen, Xingchen Wu, Dan Ma, Xiaohua Zhang, Ruizhen Li, Cong Han, Haixin Liu, Xiangrui Yin, Qian Du, Dewen Tong, Yong Huang,

Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009940]

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HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration.

Anabel Guedán, Callum D Donaldson, Eve R Caroe, Ophélie Cosnefroy, Ian A Taylor, Kate N Bishop,

The capsid (CA) lattice of the HIV-1 core plays a key role during infection. From the moment the core is released into the cytoplasm, it interacts with a range of cellular factors that, ultimately, direct the pre-integration complex to the integration site. For integration to occur, the CA lattice must ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009484]

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Structural basis for antibody binding to adenylate cyclase toxin reveals RTX linkers as neutralization-sensitive epitopes.

Jory A Goldsmith, Andrea M DiVenere, Jennifer A Maynard, Jason S McLellan,

RTX leukotoxins are a diverse family of prokaryotic virulence factors that are secreted by the type 1 secretion system (T1SS) and target leukocytes to subvert host defenses. T1SS substrates all contain a C-terminal RTX domain that mediates recruitment to the T1SS and drives secretion via a Brownian ratchet mechanism. Neutralizing ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009920]

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Phase separation of a plant virus movement protein and cellular factors support virus-host interactions.

Shelby L Brown, Dana J Garrison, Jared P May,

Both cellular and viral proteins can undergo phase separation and form membraneless compartments that concentrate biomolecules. The p26 movement protein from single-stranded, positive-sense Pea enation mosaic virus 2 (PEMV2) separates into a dense phase in nucleoli where p26 and related orthologues must interact with fibrillarin (Fib2) as a pre-requisite for ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009622]

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The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands.

Sebastian Hutchinson, Sophie Foulon, Aline Crouzols, Roberta Menafra, Brice Rotureau, Andrew D Griffiths, Philippe Bastin,

The long and complex Trypanosoma brucei development in the tsetse fly vector culminates when parasites gain mammalian infectivity in the salivary glands. A key step in this process is the establishment of monoallelic variant surface glycoprotein (VSG) expression and the formation of the VSG coat. The establishment of VSG monoallelic ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009904]

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TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation.

Suyan Wang, Mengmeng Yu, Aijing Liu, Yuanling Bao, Xiaole Qi, Li Gao, Yuntong Chen, Peng Liu, Yulong Wang, Lixiao Xing, Lingzhai Meng, Yu Zhang, Linjin Fan, Xinyi Li, Qing Pan, Yanping Zhang, Hongyu Cui, Kai Li, Changjun Liu, Xijun He, Yulong Gao, Xiaomei Wang,

Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3-6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009900]

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Corallicolids: The elusive coral-infecting apicomplexans.

Patrick J Keeling, Varsha Mathur, Waldan K Kwong,

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009845]

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Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques.

Margherita Rosati, Mahesh Agarwal, Xintao Hu, Santhi Devasundaram, Dimitris Stellas, Bhabadeb Chowdhury, Jenifer Bear, Robert Burns, Duncan Donohue, Laurent Pessaint, Hanne Andersen, Mark G Lewis, Evangelos Terpos, Meletios Athanasios Dimopoulos, Alexander Wlodawer, James I Mullins, David J Venzon, George N Pavlakis, Barbara K Felber,

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009701]

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Trypanosoma brucei triggers a broad immune response in the adipose tissue.

Henrique Machado, Tiago Bizarra-Rebelo, Mariana Costa-Sequeira, Sandra Trindade, Tânia Carvalho, Filipa Rijo-Ferreira, Barbara Rentroia-Pacheco, Karine Serre, Luisa M Figueiredo,

Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009933]

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Protective CD4+ Th1 cell-mediated immunity is reliant upon execution of effector function prior to the establishment of the pathogen niche.

Leah S Hohman, Zhirong Mou, Matheus B Carneiro, Gabriel Ferland, Rachel M Kratofil, Paul Kubes, Jude E Uzonna, Nathan C Peters,

Intracellular infection with the parasite Leishmania major features a state of concomitant immunity in which CD4+ T helper 1 (Th1) cell-mediated immunity against reinfection coincides with a chronic but sub-clinical primary infection. In this setting, the rapidity of the Th1 response at a secondary site of challenge in the skin ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009944]

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Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways.

Uri Mbonye, Konstantin Leskov, Meenakshi Shukla, Saba Valadkhan, Jonathan Karn,

The switch between HIV latency and productive transcription is regulated by an auto-feedback mechanism initiated by the viral trans-activator Tat, which functions to recruit the host transcription elongation factor P-TEFb to proviral HIV. A heterodimeric complex of CDK9 and one of three cyclin T subunits, P-TEFb is expressed at vanishingly ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009581]

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Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis.

Jae Hak Son, Brian L Weiss, Daniela I Schneider, Kiswend-Sida M Dera, Fabian Gstöttenmayer, Robert Opiro, Richard Echodu, Norah P Saarman, Geoffrey M Attardo, Maria Onyango, Adly M M Abdalla, Serap Aksoy,

Tsetse flies (Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host's metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma, was recently discovered to reside within multiple tissues of ... Read more >>

PLoS Pathog (PLoS pathogens)
[2021, 17(9):e1009539]

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