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Peilin Wang, Yang Liu, Guangshun Zhang, Shaobo Wang, Jiao Guo, Junyuan Cao, Xiaoying Jia, Leike Zhang, Gengfu Xiao, Wei Wang
Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae ) and causes severe hemorrhagic fever in humans. At present, there are no Food and Drug Administration (FDA)-approved drugs or vaccines specific for LASV. Herein, high-throughput screening of an FDA-approved drug library was performed against LASV entry by using pseudotype virus bearing LASV envelope glycoprotein (GPC). Two hit compounds, lacidipine and phenothrin, were identified as LASV entry inhibitors in the micromolar range. A mechanistic study revealed that both compounds inhibited LASV entry by blocking low-pH-induced membrane fusion...
June 13, 2018: Journal of Virology
Kyle Rosenke, Heinz Feldmann, Jonna B Westover, Patrick William Hanley, Cynthia Martellaro, Friederike Feldmann, Greg Saturday, Jamie Lovaglio, Dana P Scott, Yousuke Furuta, Takashi Komeno, Brian B Gowen, David Safronetz
Lassa virus, the cause of Lassa fever in humans, is endemic to West Africa. Treatment of Lassa fever is primarily supportive, although ribavirin has shown limited efficacy if administered early during infection. We tested favipiravir in Lassa virus-viremic macaques and found that 300 mg/kg daily for 2 weeks successfully treated infection.
September 17, 2018: Emerging Infectious Diseases
Rachel B Brouillette, Elisabeth K Phillips, Radhika Patel, Wadie Mahauad-Fernandez, Sven Moller-Tank, Kai J Rogers, Jacob A Dillard, Ashley L Cooney, Luis Martinez-Sobrido, Chioma Okeoma, Wendy Maury
Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year. LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor, α-dystroglycan (αDG). Yet, cells lacking αDG are permissive to LASV infection, suggesting that alternative receptors exist. Previous studies demonstrate that phosphatidylserine (PtdSer)-binding receptors, Axl and Tyro3 along with C-type lectin receptors, mediate αDG-independent entry...
June 6, 2018: Journal of Virology
Sarah Moeschler, Samira Locher, Gert Zimmer
Cellular kinases are crucial for the transcription/replication of many negative-strand RNA viruses and might serve as targets for antiviral therapy. In this study, a library comprising 80 kinase inhibitors was screened for antiviral activity against vesicular stomatitis virus (VSV), a prototype member of the family Rhabdoviridae . 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125), an inhibitor of eukaryotic elongation factor 2 (eEF2) kinase, significantly inhibited entry of single-cycle VSV encoding a luciferase reporter...
June 5, 2018: Viruses
Kathryn M Hastie, Erica Ollmann Saphire
The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery...
May 26, 2018: Current Opinion in Virology
Markus H Kainulainen, Jessica R Spengler, Stephen R Welch, JoAnn D Coleman-McCray, Jessica R Harmon, John D Klena, Stuart T Nichol, César G Albariño, Christina F Spiropoulou
Lassa fever is a viral zoonosis that can be transmitted from person to person, especially in the hospital setting. The disease is endemic to several countries in West Africa and can be a major contributor to morbidity and mortality in affected areas. There are no approved vaccines to prevent Lassa virus infection. In this work, we present a vaccine candidate that combines the scalability and efficacy benefits of a live vaccine with the safety benefits of single-cycle replication. The system consists of Lassa virus replicon particles devoid of the virus essential glycoprotein gene, and a cell line that expresses the glycoprotein products, enabling efficient vaccine propagation...
May 25, 2018: Journal of Infectious Diseases
Anna Grahn, Andreas Bråve, Thomas Tolfvenstam, Marie Studahl
Nosocomial transmission of Lassa virus (LASV) is reported to be low when care for the index patient includes proper barrier nursing methods. We investigated whether asymptomatic LASV infection occurred in healthcare workers who used standard barrier nursing methods during the first 15 days of caring for a patient with Lassa fever in Sweden. Of 76 persons who were defined as having been potentially exposed to LASV, 53 provided blood samples for detection of LASV IgG. These persons also responded to a detailed questionnaire to evaluate exposure to different body fluids from the index patient...
June 2018: Emerging Infectious Diseases
Rebecca J Eisen, Linda A Atiku, Karen A Boegler, Joseph T Mpanga, Russell E Enscore, Katherine MacMillan, Kenneth L Gage
Rodents pose a significant threat to human health, particularly in rural subsistence farming communities in Africa, where rodents threaten food security and serve as reservoirs of human pathogens, including the agents of plague, leptospirosis, murine typhus, rat-bite fever, Lassa fever, salmonellosis, and campylobacteriosis. Our study focused on the plague-endemic West Nile region of Uganda, where a majority of residents live in Uganda government-defined poverty, rely on subsistence farming for a living, and frequently experience incursions of rodents into their homes...
May 16, 2018: Vector Borne and Zoonotic Diseases
Miranda J Delahoy, Breanna Wodnik, Lydia McAliley, Gauthami Penakalapati, Jenna Swarthout, Matthew C Freeman, Karen Levy
Animals found in close proximity to humans in low-and middle-income countries (LMICs) harbor many pathogens capable of infecting humans, transmissible via their feces. Contact with animal feces poses a currently unquantified-though likely substantial-risk to human health. In LMIC settings, human exposure to animal feces may explain some of the limited success of recent water, sanitation, and hygiene interventions that have focused on limiting exposure to human excreta, with less attention to containing animal feces...
March 15, 2018: International Journal of Hygiene and Environmental Health
Fatima Amanat, James Duehr, Lisa Oestereich, Kathryn M Hastie, Erica Ollmann Saphire, Florian Krammer
Arenaviruses pose a major public health threat and cause numerous infections in humans each year. Although most viruses belonging to this family do not cause disease in humans, some arenaviruses, such as Lassa virus and Machupo virus, are the etiological agents of lethal hemorrhagic fevers. The absence of a currently licensed vaccine and the highly pathogenic nature of these viruses both make the necessity of developing viable vaccines and therapeutics all the more urgent. Arenaviruses have a single glycoprotein on the surface of virions, the glycoprotein complex (GPC), and this protein can be used as a target for vaccine development...
June 27, 2018: MSphere
Matthew L Boisen, Jessica N Hartnett, Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John Demby Sandi, Mohamed Fullah, Diana K S Nelson, Duane J Bush, Megan M Rowland, Megan L Heinrich, Anatoliy P Koval, Robert W Cross, Kayla G Barnes, Anna E Lachenauer, Aaron E Lin, Mahan Nekoui, Dylan Kotliar, Sarah M Winnicki, Katherine J Siddle, Michael Gbakie, Mbalu Fonnie, Veronica J Koroma, Lansana Kanneh, Peter C Kulakosky, Kathryn M Hastie, Russell B Wilson, Kristian G Andersen, Onikepe O Folarin, Christian T Happi, Pardis C Sabeti, Thomas W Geisbert, Erica Ollmann Saphire, S Humarr Khan, Donald S Grant, John S Schieffelin, Luis M Branco, Robert F Garry
Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient's clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR...
April 12, 2018: Scientific Reports
Martin Gabriel, Donatus I Adomeh, Jacqueline Ehimuan, Jennifer Oyakhilome, Emmanuel O Omomoh, Yemisi Ighodalo, Thomas Olokor, Kofi Bonney, Meike Pahlmann, Petra Emmerich, Michaela Lelke, Linda Brunotte, Stephan Ölschläger, Corinna Thomé-Bolduan, Beate Becker-Ziaja, Carola Busch, Ikponmwosa Odia, Ephraim Ogbaini-Emovon, Peter O Okokhere, Sylvanus A Okogbenin, George O Akpede, Herbert Schmitz, Danny A Asogun, Stephan Günther
BACKGROUND: The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen. METHODOLOGY/PRINCIPAL FINDINGS: The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody-antigen complexes using rheumatoid factor or Fc gamma receptor CD32a...
March 2018: PLoS Neglected Tropical Diseases
Xavier Carnec, Mathieu Mateo, Audrey Page, Stéphanie Reynard, Jimmy Hortion, Caroline Picard, Elsie Yekwa, Laura Barrot, Stéphane Barron, Audrey Vallve, Hervé Raoul, Caroline Carbonnelle, François Ferron, Sylvain Baize
Several Old World and New World arenaviruses are responsible for severe endemic and epidemic hemorrhagic fevers, whereas other members of the Arenaviridae family are nonpathogenic. To date, no approved vaccines, antivirals, or specific treatments are available, except for Junín virus. However, protection of nonhuman primates against Lassa fever virus (LASV) is possible through the inoculation of the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with LASV. We reasoned that this virus, modified by using reverse genetics, would represent the basis for the generation of a vaccine platform against LASV and other pathogenic arenaviruses...
June 15, 2018: Journal of Virology
Masaharu Iwasaki, Juan C de la Torre
Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis...
June 1, 2018: Journal of Virology
Leslie Roberts
No abstract text is available yet for this article.
March 16, 2018: Science
The Lancet Infectious Diseases
No abstract text is available yet for this article.
April 2018: Lancet Infectious Diseases
Hoai J Hallam, Steven Hallam, Sergio E Rodriguez, Alan D T Barrett, David W C Beasley, Arlene Chua, Thomas G Ksiazek, Gregg N Milligan, Vaseeharan Sathiyamoorthy, Lisa M Reece
Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens...
2018: NPJ vaccines
Joachim Mariën, Fodé Kourouma, N'Faly Magassouba, Herwig Leirs, Elisabeth Fichet-Calvet
The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa arenavirus, the etiological agent of Lassa fever in humans. Because there exists no vaccine for human use, rodent control and adjusting human behavior are currently considered to be the only options for Lassa fever control. In order to develop efficient rodent control programs, more information about the host's ecology is needed. In this study, we investigated the spatial behavior of M. natalensis and other small rodents in two capture-mark-recapture and four dyed bait (Rhodamine B) experiments in Lassa fever-endemic villages in Upper Guinea...
March 23, 2018: EcoHealth
Amy Maxmen
No abstract text is available yet for this article.
March 22, 2018: Nature
Leen Delang, Rana Abdelnabi, Johan Neyts
Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections. The drug is converted intracellularly into its active, phosphoribosylated form, which is recognized as a substrate by the viral RNA-dependent RNA polymerase. Interestingly, besides its anti-influenza virus activity, this molecule is also able to inhibit the replication of flavi-, alpha-, filo-, bunya-, arena-, noro-, and of other RNA viruses, which include neglected and (re)emerging viruses for which no antiviral therapy is currently available...
May 2018: Antiviral Research
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