4,827 results match your criteria Arenaviruses

Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals.

Nat Microbiol 2021 Jun 14. Epub 2021 Jun 14.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.

Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, the multifunctional Z protein interacts with the L polymerase to shut down RNA synthesis and initiate virion assembly. Read More

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The board is set, the pieces are moving: Modulation of New World arenavirus entry by host proteins.

PLoS Pathog 2021 Jun 10;17(6):e1009605. Epub 2021 Jun 10.

Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States of America.

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Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways.

PLoS Pathog 2021 06 7;17(6):e1009662. Epub 2021 Jun 7.

University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.

Signal-regulatory protein alpha (SIRPA) is a well-known inhibitor of phagocytosis when it complexes with CD47 expressed on target cells. Here we show that SIRPA decreased in vitro infection by a number of pathogenic viruses, including New World and Old World arenaviruses, Zika virus, vesicular stomatitis virus and pseudoviruses bearing the Machupo virus, Ebola virus and SARS-CoV-2 glycoproteins, but not HSV-1, MLV or mNoV. Moreover, mice with targeted mutation of the Sirpa gene that renders it non-functional were more susceptible to infection with the New World arenaviruses Junín virus vaccine strain Candid 1 and Tacaribe virus, but not MLV or mNoV. Read More

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Validation of Inactivation Methods for Arenaviruses.

Viruses 2021 May 24;13(6). Epub 2021 May 24.

Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Several of the human-pathogenic arenaviruses cause hemorrhagic fever and have to be handled under biosafety level 4 conditions, including Lassa virus. Rapid and safe inactivation of specimens containing these viruses is fundamental to enable downstream processing for diagnostics or research under lower biosafety conditions. We established a protocol to test the efficacy of inactivation methods using the low-pathogenic Morogoro arenavirus as surrogate for the related highly pathogenic viruses. Read More

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Activation of the STAT3 Signaling Pathway by the RNA-Dependent RNA Polymerase Protein of Arenavirus.

Viruses 2021 May 25;13(6). Epub 2021 May 25.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China.

Arenaviruses cause chronic and asymptomatic infections in their natural host, rodents, and several arenaviruses cause severe hemorrhagic fever that has a high mortality in infected humans, seriously threatening public health. There are currently no FDA-licensed drugs available against arenaviruses; therefore, it is important to develop novel antiviral strategies to combat them, which would be facilitated by a detailed understanding of the interactions between the viruses and their hosts. To this end, we performed a transcriptomic analysis on cells infected with arenavirus lymphocytic choriomeningitis virus (LCMV), a neglected human pathogen with clinical significance, and found that the signal transducer and activator of transcription 3 (STAT3) signaling pathway was activated. Read More

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Experimental Morogoro Virus Infection in Its Natural Host, .

Viruses 2021 05 7;13(5). Epub 2021 May 7.

Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely (). In this study, we investigated the history of infection and virus transmission within the natural host population. Read More

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Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family.

Heliyon 2021 May 19;7(5):e07022. Epub 2021 May 19.

Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh.

Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. Read More

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Molecular characterization of a new highly divergent Mobala related arenavirus isolated from Praomys sp. rodents.

Sci Rep 2021 May 13;11(1):10188. Epub 2021 May 13.

The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai - Chinese Academy of Sciences, Discovery and Molecular Characterization of Pathogens, Shanghai, 200031, China.

Arenaviruses represent a family of viruses that are naturally present in rodents belonging to subfamily Murinae, Neotominae or Sigmodontinae. Except for Lassa virus, little information is available on other Old-World arenaviruses. Here, we describe strain AnRB3214, a virus isolated from a presumed Praomys sp. Read More

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Discovery of a novel highly potent broad-spectrum heterocyclic chemical series of arenavirus cell entry inhibitors.

Bioorg Med Chem Lett 2021 Jun 5;41:127983. Epub 2021 May 5.

Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego 92121, CA, United States. Electronic address:

We identified and explored the structure-activity relationship (SAR) of a novel heterocyclic chemical series of arenavirus cell entry inhibitors. Optimized lead compounds, including diphenyl-substituted imidazo[1,2-a]pyridines, benzimidazoles, and benzotriazoles exhibited low to sub-nanomolar potency against both pseudotyped and infectious Old and New World arenaviruses, attractive metabolic stability in human and most nonhuman liver microsomes as well as a lack of hERG K + channel or CYP enzyme inhibition. Moreover, the straightforward synthesis of several lead compounds (e. Read More

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Second-Generation Live-Attenuated Candid#1 Vaccine Virus Resists Reversion and Protects against Lethal Junín Virus Infection in Guinea Pigs.

J Virol 2021 Jun 24;95(14):e0039721. Epub 2021 Jun 24.

Montana Biotechnology Center, University of Montana, Missoula, Montana, USA.

Live-attenuated virus vaccines are highly effective in preventing viral disease but carry intrinsic risks of residual virulence and reversion to pathogenicity. The classically derived Candid#1 virus protects seasonal field workers in Argentina against zoonotic infection by Junín virus (JUNV) but is not approved in the United States, in part due to the potential for reversion at the attenuating locus, a phenylalanine-to-isoleucine substitution at position 427 in the GP2 subunit of the GPC envelope glycoprotein. Previously, we demonstrated facile reversion of recombinant Candid#1 (rCan) in cell culture and identified an epistatic interaction between the attenuating I427 and a secondary K33S mutation in the stable signal peptide (SSP) subunit of GPC that imposes an evolutionary barrier to reversion. Read More

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Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses.

Viruses 2021 04 16;13(4). Epub 2021 Apr 16.

Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.

Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficacious antiviral agents an urgent need. Inhibiting viral attachment and entry is a promising strategy for the development of new treatments and to prevent all subsequent steps in virus infection. Read More

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Special Issue "Arenaviruses 2020".

Viruses 2021 04 18;13(4). Epub 2021 Apr 18.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to murid subfamily (New World arenaviruses) [... Read More

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A unified atlas of CD8 T cell dysfunctional states in cancer and infection.

Mol Cell 2021 06 22;81(11):2477-2493.e10. Epub 2021 Apr 22.

Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Read More

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Therapy for Argentine hemorrhagic fever in nonhuman primates with a humanized monoclonal antibody.

Proc Natl Acad Sci U S A 2021 03;118(11)

Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555.

The COVID-19 pandemic has reemphasized the need to identify safe and scalable therapeutics to slow or reverse symptoms of disease caused by newly emerging and reemerging viral pathogens. Recent clinical successes of monoclonal antibodies (mAbs) in therapy for viral infections demonstrate that mAbs offer a solution for these emerging biothreats. We have explored this with respect to Junin virus (JUNV), an arenavirus classified as a category A high-priority agent and the causative agent of Argentine hemorrhagic fever (AHF). Read More

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Crystal structures of β-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies.

Acta Crystallogr D Struct Biol 2021 Apr 30;77(Pt 4):486-495. Epub 2021 Mar 30.

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. Read More

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Construction and Immunological Evaluation of an Adenoviral Vector-Based Vaccine Candidate for Lassa Fever.

Viruses 2021 03 15;13(3). Epub 2021 Mar 15.

Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.

Lassa virus (LASV) is a rodent-borne arenavirus circulating in West African regions that causes Lassa fever (LF). LF is normally asymptomatic at the initial infection stage, but can progress to severe disease with multiorgan collapse and hemorrhagic fever. To date, the therapeutic choices are limited, and there is no approved vaccine for avoiding LASV infection. Read More

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The Janus Kinase Inhibitor Ruxolitinib Prevents Terminal Shock in a Mouse Model of Arenavirus Hemorrhagic Fever.

Microorganisms 2021 Mar 9;9(3). Epub 2021 Mar 9.

Department of Biomedicine-Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland.

Arenaviruses such as Lassa virus cause arenavirus hemorrhagic fever (AVHF), but protective vaccines and effective antiviral therapy remain unmet medical needs. Our prior work has revealed that inducible nitric oxide synthase (iNOS) induction by IFN-γ represents a key pathway to microvascular leak and terminal shock in AVHF. Here we hypothesized that Ruxolitinib, an FDA-approved JAK inhibitor known to prevent IFN-γ signaling, could be repurposed for host-directed therapy in AVHF. Read More

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Phylogenetic and Mutational Analysis of Lassa Virus Strains Isolated in Nigeria: Proposal for an In Silico Study.

JMIR Res Protoc 2021 Mar 26;10(3):e23015. Epub 2021 Mar 26.

Department of Natural and Environmental Sciences, American University of Nigeria, Yola, Nigeria.

Background: In 2018, the total number of Lassa fever cases in Nigeria was significantly higher than that observed in previous years. Hence, studies had attempted to determine the underlying cause. However, reports using phylogenetic methods to analyze this finding ruled out the emergence of potentially more transmissible Lassa virus strains or an increase in human-to-human viral transmission as the cause underlying the increase in cases. Read More

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Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack.

Cell Rep Med 2021 Mar 3;2(3):100209. Epub 2021 Mar 3.

University of Basel, Department of Biomedicine, Basel, Switzerland.

Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8 T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. Read More

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Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study.

Lancet Glob Health 2021 04;9(4):e469-e478

Inserm 1219, University of Bordeaux, and French National Research Institute for Sustainable Development, Bordeaux, France; Department of Infectious Diseases and Tropical Medicine, Division of Tropical Medicine and Clinical International Health, University Hospital Centre of Bordeaux, Hôpital Pellegrin, Bordeaux, France; Programme PAC-CI/ANRS Research Site, University Hospital Centre of Treichville, Abidjan, Côte d'Ivoire.

Background: Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. Read More

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Hunting and consumption of rodents by children in the Lassa fever endemic area of Faranah, Guinea.

PLoS Negl Trop Dis 2021 03 17;15(3):e0009212. Epub 2021 Mar 17.

Center for International Health Protection, Robert Koch Institute, Berlin, Germany.

As a consequence of the Ebola outbreak, human-animal contact has gained importance for zoonotic transmission surveillance. In Faranah (Upper Guinea), daily life is intertwined with rodents, such as the Natal multimammate mouse, Mastomys natalensis; a reservoir for Lassa virus (LASV). However, this contact is rarely perceived as a health risk by residents, although Lassa fever (LF) is known to be endemic to this region. Read More

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Structural analysis of viral ExoN domains reveals polyphyletic hijacking events.

PLoS One 2021 17;16(3):e0246981. Epub 2021 Mar 17.

Facultad de Ciencias, Universidad Nacional Autónoma de México, México City, México.

Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3'-5' exonuclease domain (ExoN). The proofreading activity of the ExoN domain has played a key role in the growth of nidoviral genomes, while in arenaviruses this domain partakes in the suppression of the host innate immune signaling. Sequence and structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times. Read More

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The reproductive number of Lassa fever: a systematic review.

J Travel Med 2021 04;28(3)

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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Opposing effects of T cell receptor signal strength on CD4 T cells responding to acute versus chronic viral infection.

Elife 2021 Mar 8;10. Epub 2021 Mar 8.

Immune Cell Biology Laboratory, Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.

A hallmark of adaptive immunity is CD4 T cells' ability to differentiate into specialized effectors. A long-standing question is whether T cell receptor (TCR) signal strength can dominantly instruct the development of Th1 and T follicular helper (Tfh) cells across distinct infectious contexts. We characterized the differentiation of murine CD4 TCR transgenic T cells responding to altered peptide ligand lymphocytic choriomeningitis viruses (LCMV) derived from acute and chronic parental strains. Read More

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Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure.

Viruses 2021 02 23;13(2). Epub 2021 Feb 23.

MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G61 1QH, UK.

The order accommodates related viruses (bunyaviruses) with segmented, linear, single-stranded, negative- or ambi-sense RNA genomes. Their glycoproteins form capsomeric projections or spikes on the virion surface and play a crucial role in virus entry, assembly, morphogenesis. Bunyavirus glycoproteins are encoded by a single RNA segment as a polyprotein precursor that is co- and post-translationally cleaved by host cell enzymes to yield two mature glycoproteins, Gn and Gc (or GP1 and GP2 in arenaviruses). Read More

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February 2021

Identification of potential novel hosts and the risk of infection with lymphocytic choriomeningitis virus in humans in Gabon, Central Africa.

Int J Infect Dis 2021 Apr 2;105:452-459. Epub 2021 Mar 2.

Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan; Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki, Japan. Electronic address:

Objectives: Lymphocytic choriomeningitis virus (LCMV), a human pathogenic arenavirus, is distributed worldwide. However, no human cases have been reported in Africa. This study aimed to investigate the current situation and potential risks of LCMV infection in Gabon, Central Africa. Read More

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Glycoprotein N-linked glycans play a critical role in arenavirus pathogenicity.

PLoS Pathog 2021 Mar 1;17(3):e1009356. Epub 2021 Mar 1.

Department of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.

Several arenaviruses cause hemorrhagic fevers in humans with high case fatality rates. A vaccine named Candid#1 is available only against Junin virus (JUNV) in Argentina. Specific N-linked glycans on the arenavirus surface glycoprotein (GP) mask important epitopes and help the virus evade antibody responses. Read More

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Bolivian hemorrhagic fever: A narrative review.

Travel Med Infect Dis 2021 Mar-Apr;40:102001. Epub 2021 Feb 25.

Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.

Bolivian hemorrhagic fever (BHF) is a sporadic high-mortality febrile illness. Two etiological agents are currently recognized: Machupo virus and Chapare virus. Infection in humans occurs by exposure to excreta and secretions of wild native rodents in Bolivia. Read More

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February 2021