ICTV Virus Taxonomy Profile: Arenaviridae 2023.

Arenaviridae is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three single-stranded RNA segments and encodes a nucleoprotein (NP), a glycoprotein (GP) and a large (L) protein containing RNA-directed RNA polymerase (RdRP) domains; some arenavirids encode a zinc-binding protein (Z). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Arenaviridae, which is available at www.ictv.global/report/arenaviridae.

Crowdsensing IoT Architecture for Pervasive Air Quality and Exposome Monitoring: Design, Development, Calibration, and Long-Term Validation.

A pervasive assessment of air quality in an urban or mobile scenario is paramount for personal or city-wide exposure reduction action design and implementation. The capability to deploy a high-resolution hybrid network of regulatory grade and low-cost fixed and mobile devices is a primary enabler for the development of such knowledge, both as a primary source of information and for validating high-resolution air quality predictive models. The capability of real-time and cumulative personal exposure monitoring is also considered a primary driver for exposome monitoring and future predictive medicine approaches. Leveraging on chemical sensing, machine learning, and Internet of Things (IoT) expertise, we developed an integrated architecture capable of meeting the demanding requirements of this challenging problem. A detailed account of the design, development, and validation procedures is reported here, along with the results of a two-year field validation effort.

ICTV Virus Taxonomy Profile: Arenaviridae.

Members of the family Arenaviridae produce enveloped virions containing genomes consisting of two or three single-stranded RNA segments totalling about 10.5 kb. Arenaviruses can infect mammals, including humans and other primates, snakes, and fish. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Arenaviridae, which is available at www.ictv.global/report/arenaviridae.

Electronic Noses for Composites Surface Contamination Detection in Aerospace Industry.

The full exploitation of Composite Fiber Reinforced Polymers (CFRP) in so-called green aircrafts design is still limited by the lack of adequate quality assurance procedures for checking the adhesive bonding assembly, especially in load-critical primary structures. In this respect, contamination of the CFRP panel surface is of significant concern since it may severely affect the bonding and the mechanical properties of the joint. During the last years, the authors have developed and tested an electronic nose as a non-destructive tool for pre-bonding surface inspection for contaminants detection, identification and quantification. Several sensors and sampling architectures have been screened in view of the high Technology Readiness Level (TRL) scenarios requirements. Ad-hoc pattern recognition systems have also been devised to ensure a fast and reliable assessment of the contamination status, by combining real time classifiers and the implementation of a suitable rejection option. Results show that e-noses could be used as first line low cost Non Destructive Test (NDT) tool in aerospace CFRP assembly and maintenance scenarios.

IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice.

Recent studies have revealed IL-33 as a key factor in promoting antiviral T-cell responses. However, it is less clear as to how IL-33 regulates innate immunity. In this study, we infected wild-type (WT) and IL-33(-/-) mice with lymphocytic choriomeningitis virus and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-γ production in the liver. We first show that IL-33 deficiency resulted in a marked reduction in the number of IFN-γ(+) γδ T and NK cells, but an increase in that of IL-17(+) γδ T cells at 16 h postinfection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-γ-producing γδ T and NK cells, and inhibiting IL-17(+) γδ T cells. We also found that rIL-33-induced type 2 innate lymphoid cells were not involved in T-cell responses and liver injury, since the adoptive transfer of type 2 innate lymphoid cells neither affected the IFN-γ and TNF-α production in T cells, nor liver transferase levels in lymphocytic choriomeningitis virus infected mice. Interestingly, we found that while IL-33 was not required for costimulatory molecule expression, it was critical for DC proliferation and cytokine production. Together, this study highlights an essential role of IL-33 in regulating innate IFN-γ-production and DC function during viral hepatitis.

Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate.

The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.

Past, present, and future of arenavirus taxonomy.

Until recently, members of the monogeneric family Arenaviridae (arenaviruses) have been known to infect only muroid rodents and, in one case, possibly phyllostomid bats. The paradigm of arenaviruses exclusively infecting small mammals shifted dramatically when several groups independently published the detection and isolation of a divergent group of arenaviruses in captive alethinophidian snakes. Preliminary phylogenetic analyses suggest that these reptilian arenaviruses constitute a sister clade to mammalian arenaviruses. Here, the members of the International Committee on Taxonomy of Viruses (ICTV) Arenaviridae Study Group, together with other experts, outline the taxonomic reorganization of the family Arenaviridae to accommodate reptilian arenaviruses and other recently discovered mammalian arenaviruses and to improve compliance with the Rules of the International Code of Virus Classification and Nomenclature (ICVCN). PAirwise Sequence Comparison (PASC) of arenavirus genomes and NP amino acid pairwise distances support the modification of the present classification. As a result, the current genus Arenavirus is replaced by two genera, Mammarenavirus and Reptarenavirus, which are established to accommodate mammalian and reptilian arenaviruses, respectively, in the same family. The current species landscape among mammalian arenaviruses is upheld, with two new species added for Lunk and Merino Walk viruses and minor corrections to the spelling of some names. The published snake arenaviruses are distributed among three new separate reptarenavirus species. Finally, a non-Latinized binomial species name scheme is adopted for all arenavirus species. In addition, the current virus abbreviations have been evaluated, and some changes are introduced to unequivocally identify each virus in electronic databases, manuscripts, and oral proceedings.

Pathogenic Old World arenaviruses inhibit TLR2/Mal-dependent proinflammatory cytokines in vitro.

Lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, and Lassa virus (LASV), the causative agent of Lassa fever (LF), have extensive strain diversity and significant variations in pathogenicity for humans and experimental animals. The WE strain of LCMV (LCMV-WE), but not the Armstrong (Arm) strain, induces a fatal LF-like disease in rhesus macaques. We also demonstrated that LASV infection of human macrophages and endothelial cells resulted in reduced levels of proinflammatory cytokines. Here we have shown that cells infected with LASV or with LCMV-WE suppressed Toll-like receptor 2 (TLR2)-dependent proinflammatory cytokine responses. The persisting isolate LCMV clone 13 (CL13) also failed to stimulate interleukin-6 (IL-6) in macrophages. In contrast, nonpathogenic Mopeia virus, which is a genetic relative of LASV and LCMV-Arm induced robust responses that were TLR2/Mal dependent, required virus replication, and were enhanced by CD14. Superinfection experiments demonstrated that the WE strain of LCMV inhibited the Arm-mediated IL-8 response during the early stage of infection. In cells transfected with the NF-κB-luciferase reporter, infection with LCMV-Arm resulted in the induction of NF-κB, but cells infected with LCMV-WE and CL13 did not. These results suggest that pathogenic arenaviruses suppress NF-κB-mediated proinflammatory cytokine responses in infected cells.

An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.

BACKGROUND: Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection. RESULTS: SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1ß, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity. CONCLUSION: SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

Cauliflower mosaic virus: Virus-host interactions and its uses in biotechnology and medicine.

Cauliflower mosaic virus (CaMV) was the first discovered plant virus with genomic DNA that uses reverse transcriptase for replication. The CaMV 35S promoter is a constitutive promoter and thus, an attractive driver of gene expression in plant biotechnology. It is used in most transgenic crops to activate foreign genes which have been artificially inserted into the host plant. In the last century, producing food for the world's population while preserving the environment and human health is the main topic of agriculture. The damage caused by viral diseases has a significant negative economic impact on agriculture, and disease control is based on two strategies: immunization and prevention to contain virus spread, so correct identification of plant viruses is important for disease management. Here, we discuss CaMV from different aspects: taxonomy, structure and genome, host plants and symptoms, transmission and pathogenicity, prevention, control and application in biotechnology as well as in medicine. Also, we calculated the CAI index for three ORFs IV, V, and VI of the CaMV virus in host plants, the results of which can be used in the discussion of gene transfer or antibody production to identify the CaMV.

Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus.

Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression once a host is exposed to the pathogen. One potential mechanism for escaping pre-existing immunity is to trigger death among antigen-activated cells. We tested whether FasL/CD178 is involved in destroying preexisting immunity. Rhesus macaques were immunized with recombinant vesicular stomatitis virus vaccine expressing SIV Gag to elicit cellular immune responses, then treated with antibody that neutralizes FasL and challenged with intravenous SIVmac251. Compared with animals injected with control antibody, anti-FasL-treated macaques had superior preservation of central memory CD4(+) and CD8(+) cells and decreased regulatory T cells in the blood. The CD4(+) and CD8(+) lymphocytes from treated animals responded better to SIV Gag compared with controls, evidenced by higher cell-mediated immune responses to viral antigens for at least 17 weeks after SIV challenge. Anti-FasL treatment during the initial stages of acute SIV infection preserved the T-cell compartment and sustained cell-mediated immunity to SIV.

The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections.

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.

Cauliflower Mosaic Virus TAV, a Plant Virus Protein That Functions like Ribonuclease H1 and is Cytotoxic to Glioma Cells.

Recent comparisons between plant and animal viruses reveal many common principles that underlie how all viruses express their genetic material, amplify their genomes, and link virion assembly with replication. Cauliflower mosaic virus (CaMV) is not infectious for human beings. Here, we show that CaMV transactivator/viroplasmin protein (TAV) shares sequence similarity with and behaves like the human ribonuclease H1 (RNase H1) in reducing DNA/RNA hybrids detected with S9.6 antibody in HEK293T cells. We showed that TAV is clearly expressed in the cytosol and in the nuclei of transiently transfected human cells, similar to its distribution in plants. TAV also showed remarkable cytotoxic effects in U251 human glioma cells in vitro. These characteristics pave the way for future analysis on the use of the plant virus protein TAV, as an alternative to human RNAse H1 during gene therapy in human cells.

Role of the Fas/FasL pathway in HIV or SIV disease.

Human immunodeficiency virus disease involves progressive destruction of host immunity leading to opportunistic infections and increased rates for malignancies. Both depletion in immune cell numbers as well as defects in their effector functions are responsible for this immunodeficiency The broad impact of HIV reflects a similarly broad pattern of cell depletion including subsets that do not express viral receptors or support viral replication. Indirect cell killing, the destruction of uninfected cells, is due partly to activation of the Fas/FasL system for cell death. This death-signaling pathway is induced during HIV disease and contributes significantly to viral pathogenesis and disease.

Gene expression in primate liver during viral hemorrhagic fever.

BACKGROUND: Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV) provide a model for human Lassa fever. Disease begins with flu-like symptoms and progresses rapidly with fatal consequences. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al J. Virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. RESULTS: Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a broader effect on liver cell function than did infection with non-virulent LCMV-Armstrong. During the first few days after infection, LCMV altered expression of genes associated with energy production, including fatty acid and glucose metabolism. The transcriptome profile resembled that of an organism in starvation: mRNA for acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis was reduced while genes for enzymes in gluconeogenesis were up-regulated. Expression was also altered for genes associated with complement and coagulation cascades, and with signaling pathways involving STAT1 and TGF-beta. CONCLUSION: Most of the 4500 differentially expressed transcripts represented a general response to both virulent and mild infections. However, approximately 250 of these transcripts had significantly different expression in virulent infections as compared to mild infections, with approximately 30 of these being differentially regulated during the pre-viremic stage of infection. The genes that are expressed early and differently in mild and virulent disease are potential biomarkers for prognosis and triage of acute viral disease.

Circulating natural killer and gammadelta T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus.

Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs). Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK) and gammadelta T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3-CD8+ or CD3-CD16+ and not the NKT (primarily CD3+CD56+) subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and gammadelta T cells, indicating that this is not a pathogenic event. V(3)9 T cells, representing the majority of circulating gammadelta T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections.

T-Cell Response to Viral Hemorrhagic Fevers.

Viral hemorrhagic fevers (VHF) are a group of clinically similar diseases that can be caused by enveloped RNA viruses primarily from the families Arenaviridae, Filoviridae, Hantaviridae, and Flaviviridae. Clinically, this group of diseases has in common fever, fatigue, dizziness, muscle aches, and other associated symptoms that can progress to vascular leakage, bleeding and multi-organ failure. Most of these viruses are zoonotic causing asymptomatic infections in the primary host, but in human beings, the infection can be lethal. Clinical and experimental evidence suggest that the T-cell response is needed for protection against VHF, but can also cause damage to the host, and play an important role in disease pathogenesis. Here, we present a review of the T-cell immune responses to VHF and insights into the possible ways to improve counter-measures for these viral agents.

A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge.

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.

Structural Transformation to Attain Responsible BIOSciences (STARBIOS2): Protocol for a Horizon 2020 Funded European Multicenter Project to Promote Responsible Research and Innovation.

BACKGROUND: Promoting Responsible Research and Innovation (RRI) is a major strategy of the "Science with and for Society" work program of the European Union's Horizon 2020 Framework Programme for Research and Innovation. RRI aims to achieve a better alignment of research and innovation with the values, needs, and expectations of society. The RRI strategy includes the "keys" of public engagement, open access, gender, ethics, and science education. The Structural Transformation to Attain Responsible BIOSciences (STARBIOS2) project promotes RRI in 6 European research institutions and universities from Bulgaria, Germany, Italy, Slovenia, Poland, and the United Kingdom, in partnership with a further 6 institutions from Brazil, Denmark, Italy, South Africa, Sweden, and the United States. OBJECTIVE: The project aims to attain RRI structural change in 6 European institutions by implementing action plans (APs) and developing APs for 3 non-European institutions active in the field of biosciences; use the implementation of APs as a learning process with a view to developing a set of guidelines on the implementation of RRI; and develop a sustainable model for RRI in biosciences. METHODS: The project comprises interrelated research and implementation designed to achieve the aforementioned specific objectives. The project is organized into 6 core work packages and 5 supporting work packages. The core work packages deal with the implementation of institutional APs in 6 European institutions based on the structural change activation model. The supporting work packages include technical assistance, learning process on RRI-oriented structural change, monitoring and assessment, communication and dissemination, and project management. RESULTS: The project is funded by Horizon 2020 and will run for 4 years (May 2016-April 2020). As of June 2018, the initial phase has been completed. The participating institutions have developed and approved APs and commenced their implementation. An observation tool has been launched by the Technical Assistance Team to collect information from the implementation of APs; the Evaluation & Assessment team has started monitoring the advancement of the project. As part of the communication and dissemination strategy, a project website, a Facebook page, and a Twitter account have been launched and are updated periodically. The International Scientific Advisory Committee has been formed to advise on the reporting and dissemination of the project's results. CONCLUSIONS: In the short term, we anticipate that the project will have a considerable impact on the organizational processes and structures, improving the RRI uptake in the participating institutions. In the medium term, we expect to make RRI-oriented organizational change scalable across Europe by developing guidelines on RRI implementation and an RRI model in biosciences. In the long term, we expect that the project would help increase the ability of research institutions to make discoveries and innovations in better alignment with societal needs and values. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11745.

Improving the Breadth of the Host's Immune Response to Lassa Virus.

In 2017, the global Coalition for Epidemic Preparedness (CEPI) declared Lassa virus disease to be one of the world's foremost biothreats. In January 2018, World Health Organization experts met to address the Lassa biothreat. It was commonly recognized that the diversity of Lassa virus (LASV) isolated from West African patient samples was far greater than that of the Ebola isolates from the West African epidemic of 2013⁻2016. Thus, vaccines produced against Lassa virus disease face the added challenge that they must be broadly-protective against a wide variety of LASV. In this review, we discuss what is known about the immune response to Lassa infection. We also discuss the approaches used to make broadly-protective influenza vaccines and how they could be applied to developing broad vaccine coverage against LASV disease. Recent advances in AIDS research are also potentially applicable to the design of broadly-protective medical countermeasures against LASV disease.