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Junin virus (JUNV) is a New World arenavirus that is the causative agent of Argentine hemorrhagic fever (AHF). Candid#1 (Can) is a live-attenuated vaccine strain of JUNV that since its introduction has resulted in a marked decrease in AHF incidence within the endemic regions of the Pampas in Argentina. Originally, the viral determinants and mechanisms of Can attenuation were not well understood. Recent work has identified the glycoprotein as the major attenuating factor for Can. The establishment of attenuating strategies based on any of the other viral proteins, however, has not been pursued. Here, we document the role of Can Z resulting in incompatibilities with wild type JUNV that results in decreased growth in vitro. In addition, this incompatibility results in attenuation of the virus in the guinea pig model. Further, we identify a single mutation (V64G) in the Z protein that is able to confer this demonstrated attenuation. By establishing and characterizing a novel attenuation strategy for New World mammarenaviruses, we hope to aid future vaccine development for related emerging pathogens including Machupo virus (MACV), Guanarito virus (GTOV), and Sabia virus (SABV). Author summary: The continual development of safe, effective vaccines against emerging diseases is one of the greatest challenges facing the scientific community. The New World group of mammarenaviruses contains multiple human pathogens, each capable of causing severe hemorrhagic disease. Among these, only Junin virus has a distributed vaccine. By utilizing this vaccine, we are able to determine vaccine development strategies for related New World viruses that represent an emerging threat. Here we demonstrate that manipulation of the viral Z protein is able to produce an incompatibility that ultimately attenuates the virus. This provides yet another tool for future vaccine development to further global public health. [ABSTRACT FROM AUTHOR]

The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice. Author Summary: The new world arenavirus Junín virus (JUNV) is the causative agent of a lethal human infectious disease, Argentine hemorrhagic fever. Laboratory mice are used as models to study many viral diseases. However, adult laboratory mice are generally resistant to JUNV infection. Interferons are early immune regulatory molecules that induce potent anti-viral status in host cells and activate host immune cells to counteract virus infection. The activity of interferons relies on their cell surface receptors. We have previously reported that mutant mice with defect in interferon receptors succumbed to challenge with JUNV, highlighting the critical role of interferon in restricting JUNV infection in mice. Here we further study the basis of mouse resistance to JUNV infection and report that the replication of both pathogenic JUNV and its vaccine strains are highly sensitive to type I IFN treatment in mouse cells. However, both strains replicate efficiently in Africa green monkey-derived Vero cells and human cells when treated with high doses of interferon. Additionally, the vaccine strain replicates less efficiently in mouse cells compared with the pathogenic strain, which might partially explain its attenuation in mice. Our new findings help better understand the JUNV-host interaction. [ABSTRACT FROM AUTHOR]

Junín virus (JUNV), an arenavirus, is the causative agent of Argentine hemorrhagic fever, an infectious human disease with 15–30% case fatality. The pathogenesis of AHF is still not well understood. Elevated levels of interferon and cytokines are reported in AHF patients, which might be correlated to the severity of the disease. However the innate immune response to JUNV infection has not been well evaluated. Previous studies have suggested that the virulent strain of JUNV does not induce IFN in human macrophages and monocytes, whereas the attenuated strain of JUNV was found to induce IFN response in murine macrophages via the TLR-2 signaling pathway. In this study, we investigated the interaction between JUNV and IFN pathway in human epithelial cells highly permissive to JUNV infection. We have determined the expression pattern of interferon-stimulated genes (ISGs) and IFN-β at both mRNA and protein levels during JUNV infection. Our results clearly indicate that JUNV infection activates the type I IFN response. STAT1 phosphorylation, a downstream marker of activation of IFN signaling pathway, was readily detected in JUNV infected IFN-competent cells. Our studies also demonstrated for the first time that RIG-I was required for IFN production during JUNV infection. IFN activation was detected during infection by either the virulent or attenuated vaccine strain of JUNV. Curiously, both virus strains were relatively insensitive to human IFN treatment. Our studies collectively indicated that JUNV infection could induce host type I IFN response and provided new insights into the interaction between JUNV and host innate immune system, which might be important in future studies on vaccine development and antiviral treatment. Author Summary: Junín virus (JUNV), which is endemic to the Argentinean Pampas region, is the causative agent of Argentine hemorrhagic fever (AHF), a severe illness with hemorrhagic and neurological manifestations and with a case fatality of 15–30%. Clinical studies demonstrate that elevated levels of interferon and cytokines are produced in AHF patients, which might be correlated to the severity of disease. However it remains unclear, especially during virus infection, how human cells can sense virus infection and respond by activation of IFN pathway. Our studies clearly demonstrated that JUNV infection could activate type I IFN response in human cells. IFN pathway activation occurred in cells infected with either virulent strain or attenuated vaccine strain of JUNV. Our data also revealed for the first time that RIG-I was required for type I IFN production during virus infection in human cells. Interestingly, both strains of JUNV were relatively insensitive to human IFN treatment, which might have implications for the role of the IFN on virus infection in vivo. Overall, these results indicate that JUNV infection could induce host IFN response and provide new insights into JUNV and host interaction as well as the mechanism underlying AHF. [ABSTRACT FROM AUTHOR]

Junín virus (JUNV), an arenavirus, is the causative agent of Argentine hemorrhagic fever, an infectious human disease with 15-30% case fatality. The pathogenesis of AHF is still not well understood. Elevated levels of interferon and cytokines are reported in AHF patients, which might be correlated to the severity of the disease. However the innate immune response to JUNV infection has not been well evaluated. Previous studies have suggested that the virulent strain of JUNV does not induce IFN in human macrophages and monocytes, whereas the attenuated strain of JUNV was found to induce IFN response in murine macrophages via the TLR-2 signaling pathway. In this study, we investigated the interaction between JUNV and IFN pathway in human epithelial cells highly permissive to JUNV infection. We have determined the expression pattern of interferon-stimulated genes (ISGs) and IFN-β at both mRNA and protein levels during JUNV infection. Our results clearly indicate that JUNV infection activates the type I IFN response. STAT1 phosphorylation, a downstream marker of activation of IFN signaling pathway, was readily detected in JUNV infected IFN-competent cells. Our studies also demonstrated for the first time that RIG-I was required for IFN production during JUNV infection. IFN activation was detected during infection by either the virulent or attenuated vaccine strain of JUNV. Curiously, both virus strains were relatively insensitive to human IFN treatment. Our studies collectively indicated that JUNV infection could induce host type I IFN response and provided new insights into the interaction between JUNV and host innate immune system, which might be important in future studies on vaccine development and antiviral treatment. [ABSTRACT FROM AUTHOR]

As the number of observations submitted to the citizen science platform iNaturalist continues to grow, it is increasingly important that these observations can be identified to the finest taxonomic level, maximizing their value for biodiversity research. Here, we explore the benefits of acting as an identifier on iNaturalist., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)