Academic literature on the topic 'Arenaviridae Infections'
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Journal articles on the topic "Arenaviridae Infections"
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Bowick, Gavin C., Susan M. Fennewald, Barry L. Elsom, Judith F. Aronson, Bruce A. Luxon, David G. Gorenstein, and Norbert K. Herzog. "Differential Signaling Networks Induced by Mild and Lethal Hemorrhagic Fever Virus Infections." Journal of Virology 80, no. 20 (October 15, 2006): 10248–52. http://dx.doi.org/10.1128/jvi.01384-06.
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ABSTRACT The family Arenaviridae includes several National Institutes of Allergy and Infections Diseases category A select agents which cause hemorrhagic fever. There are few vaccines available, and treatment is limited to ribavirin, which varies in efficacy. Development of new antiviral compounds has been hindered by a lack of understanding of the molecular basis of pathogenesis. We used two variants of Pichinde virus, one attenuated and one virulent in the guinea pig model, to delineate the host determinants which lead to either viral clearance or lethal disease. By analyzing protein level changes using pathway analysis, we have identified key intermediates which may be targets for therapeutic intervention.
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Perdomo-Celis, Federico, Maria S. Salvato, Sandra Medina-Moreno, and Juan C. Zapata. "T-Cell Response to Viral Hemorrhagic Fevers." Vaccines 7, no. 1 (January 22, 2019): 11. http://dx.doi.org/10.3390/vaccines7010011.
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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.
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Mantlo, Paessler, and Huang. "Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses." Vaccines 7, no. 4 (October 2, 2019): 138. http://dx.doi.org/10.3390/vaccines7040138.
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The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.
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Kim, Yu-Jin, Beatrice Cubitt, Yingyun Cai, Jens H. Kuhn, Daniel Vitt, Hella Kohlhof, and Juan C. de la Torre. "Novel Dihydroorotate Dehydrogenase Inhibitors with Potent Interferon-Independent Antiviral Activity against Mammarenaviruses In Vitro." Viruses 12, no. 8 (July 29, 2020): 821. http://dx.doi.org/10.3390/v12080821.
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Mammarenaviruses cause chronic infections in rodents, which are their predominant natural hosts. Human infection with some of these viruses causes high-consequence disease, posing significant issues in public health. Currently, no FDA-licensed mammarenavirus vaccines are available, and anti-mammarenavirus drugs are limited to an off-label use of ribavirin, which is only partially efficacious and associated with severe side effects. Dihydroorotate dehydrogenase (DHODH) inhibitors, which block de novo pyrimidine biosynthesis, have antiviral activity against viruses from different families, including Arenaviridae, the taxonomic home of mammarenaviruses. Here, we evaluate five novel DHODH inhibitors for their antiviral activity against mammarenaviruses. All tested DHODH inhibitors were potently active against lymphocytic choriomeningitis virus (LCMV) (half-maximal effective concentrations [EC50] in the low nanomolar range, selectivity index [SI] > 1000). The tested DHODH inhibitors did not affect virion cell entry or budding, but rather interfered with viral RNA synthesis. This interference resulted in a potent interferon-independent inhibition of mammarenavirus multiplication in vitro, including the highly virulent Lassa and Junín viruses.
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Pattabhi, Sowmya, Courtney R. Wilkins, Ran Dong, Megan L. Knoll, Jeffrey Posakony, Shari Kaiser, Chad E. Mire, et al. "Targeting Innate Immunity for Antiviral Therapy through Small Molecule Agonists of the RLR Pathway." Journal of Virology 90, no. 5 (December 16, 2015): 2372–87. http://dx.doi.org/10.1128/jvi.02202-15.
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ABSTRACTThe cellular response to virus infection is initiated when pathogen recognition receptors (PRR) engage viral pathogen-associated molecular patterns (PAMPs). This process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory factor 3 (IRF3). IRF3 plays a critical role in antiviral immunity to drive the expression of innate immune response genes, including those encoding antiviral factors, type 1 interferon, and immune modulatory cytokines, that act in concert to restrict virus replication. Thus, small molecule agonists that can promote IRF3 activation and induce innate immune gene expression could serve as antivirals to induce tissue-wide innate immunity for effective control of virus infection. We identified small molecule compounds that activate IRF3 to differentially induce discrete subsets of antiviral genes. We tested a lead compound and derivatives for the ability to suppress infections caused by a broad range of RNA viruses. Compound administration significantly decreased the viral RNA load in cultured cells that were infected with viruses of the familyFlaviviridae, including West Nile virus, dengue virus, and hepatitis C virus, as well as viruses of the familiesFiloviridae(Ebola virus),Orthomyxoviridae(influenza A virus),Arenaviridae(Lassa virus), andParamyxoviridae(respiratory syncytial virus, Nipah virus) to suppress infectious virus production. Knockdown studies mapped this response to the RIG-I-like receptor pathway. This work identifies a novel class of host-directed immune modulatory molecules that activate IRF3 to promote host antiviral responses to broadly suppress infections caused by RNA viruses of distinct genera.IMPORTANCEIncidences of emerging and reemerging RNA viruses highlight a desperate need for broad-spectrum antiviral agents that can effectively control infections caused by viruses of distinct genera. We identified small molecule compounds that can selectively activate IRF3 for the purpose of identifying drug-like molecules that can be developed for the treatment of viral infections. Here, we report the discovery of a hydroxyquinoline family of small molecules that can activate IRF3 to promote cellular antiviral responses. These molecules can prophylactically or therapeutically control infection in cell culture by pathogenic RNA viruses, including West Nile virus, dengue virus, hepatitis C virus, influenza A virus, respiratory syncytial virus, Nipah virus, Lassa virus, and Ebola virus. Our study thus identifies a class of small molecules with a novel mechanism to enhance host immune responses for antiviral activity against a variety of RNA viruses that pose a significant health care burden and/or that are known to cause infections with high case fatality rates.
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Stepanov, A. V., A. L. Buzmakova, A. V. Potapova, M. A. Yudin, and V. Ya Apchel. "Hemorrhagic fevers of viral nature. State of the problem and directions for creating effective means of prevention and treatment." Bulletin of the Russian Military Medical Academy 22, no. 3 (December 15, 2020): 182–87. http://dx.doi.org/10.17816/brmma50557.
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Abstract. An attempt to summarize the data of available information materials on epidemiological aspects, the state and prospects of prevention and treatment of hemorrhagic fevers was. Hemorrhagic fevers of viral nature-zoonotic diseases caused by viruses containing ribonucleic acid are classified into 4 families: Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. They are spread all over the world, and their pathogens are easily transmitted from person to person, thereby spreading quickly enough beyond the main focus of biological infection. That is why the causative agents of hemorrhagic fevers are regarded as highly contagious biological agents, and agents bioterrorism. Unfortunately, there are currently no effective means of specific prevention and treatment of these infections, and therapeutic measures are limited to the use of symptomatic means. In this regard, the search for substances with pronounced antiviral activity against pathogens of hemorrhagic fevers that can effectively protect against these infections, as well as prevent their occurrence and spread is one of the priority areas of research in modern Infectology, and with the involvement of modern achievements in the field of molecular Virology and genetic engineering. The data obtained in this regard allow a more in-depth understanding of the pathogenesis of hemorrhagic fevers, the mechanisms of interaction of the pathogen with the host at the cellular level, the mechanisms of intracellular replication of viruses, the formation of the hosts response to viral invasion and clinical manifestations of diseases.
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Petrov, A. A., V. N. Lebedev, T. M. Plekhanova, L. F. Stobva, O. N. Sidorova, E. V. Mel’Nikova, and S. V. Borisevich. "Future Developments and Applications of the Vaccines against Dangerous Viral Infections, RNA-Replicon-Based, Obtained from the Venezuelan Equine Encephalomyelitis Virus." Problems of Particularly Dangerous Infections, no. 3 (September 20, 2014): 86–91. http://dx.doi.org/10.21055/0370-1069-2014-3-86-91.
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The members of the Filoviridae (Marburg and Ebola viruses) and Arenaviridae (Lassa, Lujo, Machupo, Junin, Guanarito, Sabia viruses) families are the etiological agents of particularly dangerous viral hemorrhagic fevers. These agents pose a potential threat to public health care in view of the possibility of their unintended import into the non-endemic regions, and thus construction of specific medical protectors as regards induced by them diseases is a pressing issue. According to leading experts, vaccination of the cohorts that fall in the risk groups is the most effective and least expensive method to prevent the development of epidemics. The review contains information on a new prospective line of protective preparations development as regards particularly dangerous viral infections - construction of alphavirus-replicon-based vaccine. Elaboration of recombinant replicons does not require cultivation of pathogenic microorganisms. RNA-replicons are distinguished by their incapacity to produce infective progeny, which is of a great importance for the development of vaccines against particularly dangerous viral hemorrhagic fevers. Advantages of alphaviral replicons over other RNA-replicons are as follows: high levels of heterologous gene expression and resistance to anti-vector immunity. RNA-replicons of alphaviruses combine the safety of inactivated, and immunogenicity of live attenuated vaccines. Alphaviruses-based replicons are suitable for express vaccine development with the purpose of specific prophylaxis of viral infectious diseases.
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Gowen, Brian B., Min-Hui Wong, Kie-Hoon Jung, Andrew B. Sanders, Michelle Mendenhall, Kevin W. Bailey, Yousuke Furuta, and Robert W. Sidwell. "In Vitro and In Vivo Activities of T-705 against Arenavirus and Bunyavirus Infections." Antimicrobial Agents and Chemotherapy 51, no. 9 (July 2, 2007): 3168–76. http://dx.doi.org/10.1128/aac.00356-07.
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ABSTRACT There is a need for the development of effective antivirals for the treatment of severe viral diseases caused by members of the virus families Bunyaviridae and Arenaviridae. The pyrazine derivative T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has demonstrated remarkable antiviral activity against influenza virus and, to a lesser degree, against some other RNA viruses (Y. Furuta, K. Takahashi, Y. Fukuda, M. Kuno, T. Kamiyama, K. Kozaki, N. Nomura, H. Egawa, S. Minami, Y. Watanabe, H. Narita, and K. Shiraki, Antimicrob. Agents Chemother., 46:977-981, 2002). Here, we report that T-705 is highly active against a panel of bunyaviruses (La Crosse, Punta Toro, Rift Valley fever, and sandfly fever viruses) and arenaviruses (Junin, Pichinde, and Tacaribe viruses) by cytopathic effect and virus yield reduction cell-based assays. The 50% effective concentrations for T-705 ranged from 5 to 30 μg/ml and 0.7 to 1.2 μg/ml against the bunyaviruses and arenaviruses examined, respectively. We also demonstrate that orally administered T-705 is efficacious in treating Punta Toro virus in the mouse and hamster infection models, as well as Pichinde virus infection in hamsters. When administered twice daily for 5 to 6 days, beginning 4 h pre- or 24 h post-Punta Toro virus challenge, a 30-mg/kg of body weight/day dose provided complete protection from death and limited viral burden and liver disease. A dose of 50 mg/kg/day was found to be optimal for treating Pichinde infection and limiting viral replication and disease severity. In general, T-705 was found to be more active than ribavirin in cell-based assays and in vivo, as reflected by substantially greater therapeutic indexes. Our results suggest that T-705 may be a viable alternative for the treatment of life-threatening bunyaviral and arenaviral infections.
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Goldsmith, C. S., H. G. Morrison, D. D. Auperin, S. G. Whitfield, and E. L. Palmer. "Vaccinia-lassa recombinant produces lassa-like inclusions." Proceedings, annual meeting, Electron Microscopy Society of America 47 (August 6, 1989): 1036–37. http://dx.doi.org/10.1017/s0424820100157164.
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Lassa virus, a member of the Arenaviridae, is the etiologic agent of Lassa fever. The virus is endemic in widespread areas of West Africa, particularly Nigeria, Liberia, and Sierra Leone. Rough estimates indicate that there are upwards of 300,000 human infections annually, resulting in approximately 5000 fatalities. A safe and effective vaccine for Lassa fever is not yet available. Recent studies in our laboratories have focused on the development of recombinant vaccinia viruses that express the nucleoprotein and envelope glycoproteins of Lassa virus as potential vaccine candidates. Tissue culture cells infected with various recombinant viruses were examined by thin-section TEH for any morphological alterations.Tissue culture cells were infected with wild-type Lassa virus or with recombinant vaccinia viruses expressing either the Lassa virus nucleoprotein (NP). the envelope glycoproteins (GPI,GP2), or NP, GPI, and GP2 in combination. Cells were fixed in 2.5% glutaraldehyde in 0.2M cacodylate buffer, postfixed in buffered 1% osmium tetroxide, and en bloc stained with 4% uranyl acetate. The samples were dehydrated and embedded in Polysciences Epon-substitute and Araldite. Sections were stained with uranyl acetate and lead citrate.
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Iannacone, Matteo, Giovanni Sitia, Masanori Isogawa, Jason K. Whitmire, Patrizia Marchese, Francis V. Chisari, Zaverio M. Ruggeri, and Luca G. Guidotti. "Platelets Mediate Clearance of Lymphocytic Choriomeningitis Virus Infection Preventing Lethal Hemorrhage." Blood 108, no. 11 (November 16, 2006): 1089. http://dx.doi.org/10.1182/blood.v108.11.1089.1089.
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Abstract Lymphocytic choriomeningitis virus (LCMV) is a noncytopathic mouse pathogen of the arenaviridae family. Acute LCMV infection in adult mice has been extensively studied and found to be systemic, essentially asymptomatic and associated with a bone marrow aplasia that produces a transient pancytopenic state. The initial lymphopenia is rapidly reversed, such that within one week of LCMV exposure the mice display lymphocytosis and clear the infection through a response mediated by virus-specific cytotoxic T cells (CTLs). In spite of the thrombocytopenia, the occurrence of hemorrhage in these animals has not been previously investigated, likely because of the lack of overt bleeding symptoms. Other arenaviruses (such as Lassa and Junin) produce systemic infections in humans and cause hemorrhagic diseases that are often lethal. Hemorrhage, mostly mucosal and cutaneous, occurs in the context of profound thrombocytopenia (characteristic of Junin infection) and/or platelet dysfunction (characteristic of Lassa infection), but without disseminated intravascular coagulation (DIC) or other coagulation defects. The pathogenesis of arenavirus infections in humans remains elusive, although disease severity has been associated with the extent of hemorrhage, impaired cellular immunity and lack of viral clearance. We recently showed that platelets may contribute to viral pathogenesis by facilitating the accumulation of virus-specific CTLs at sites of infection. Thus, we reasoned that the thrombocytopenia and/or platelet dysfunction that typify arenavirus infections in humans might not only predispose to the development of hemorrhage but also compromise CTL-mediated viral clearance. Here we report our studies based on the model of LCMV infection in mice. We found that normal inbred mice infected with different isolates of LCMV develop thrombocytopenia associated with decreased platelet function, but show only limited mucosal hemorrhage prior to CD8+ T cell-mediated viral clearance. In contrast, mice depleted of platelets, but not those given anticoagulant treatment, fail to produce a normal CD8+ T cell response or clear LCMV; instead, they develop an interferon (IFN)-α/β-dependent lethal hemorrhagic infection. Transfusion of normal but not activation-blocked platelets into these animals restored the CD8+ T cell responses and allowed clearance of the infection, preventing hemorrhage and death. These results indicate that activated platelets are required for CD8+ T cells to clear LCMV infection and for protecting the host against the induction of an IFN-α/β-dependent, lethal hemorrhagic diathesis.
Dissertations / Theses on the topic "Arenaviridae Infections"
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Hayward, Andrea Rosemary. "The experience of a nurse who survived a highly pathogenic novel arenavirus." Thesis, 2015. http://hdl.handle.net/10539/19469.
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A dissertation submitted to the
Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree
of
Master of Science in Nursing
Johannesburg, 2015The purpose of the study was to explore and describe the experience of a nurse in a private sector hospital after contracting a highly pathogenic novel haemorrhagic fever from a patient and to explore the context of the environment in which she was cared for. Patients with complications from severe acute febrile diseases are admitted to intensive care units. During 2008, two patients with an unidentified disease were airlifted from Zambia and admitted to a private sector hospital in Johannesburg, South Africa. Four of five patients died in the outbreak before a diagnosis of Lujo virus was confirmed. Countries to the North and West of South Africa are known to be endemic areas of Viral Haemorrhagic Fevers (VHF). This puts South Africa at risk for imported VHF and future outbreaks. The sole survivor was able to share useful advice for future implementation from experiences during the period of her illness. Unique challenges of the management and environment of this outbreak may assist in future outbreaks. A bounded single case study design using mixed multiple qualitative approaches including phenomenology was used to underpin and guide the study of the participant’s experience. The participant’s reflection was subjected to in-depth analysis using Colaizzi’s framework. Triangulation using the reflection of the contents of the “Outbreak diary” – a journal kept by members of the managing team and clinical nursing records was undertaken. Emerging themes were grouped into four main themes: Initial contact with the source; Admission is inevitable; Moments of care and Always involved, which have been discussed in depth. The information gleaned from these themes can be applied to practice in future. The safety of patients and staff in an outbreak depends on attention to detail. History taking was identified as crucial for appropriate infection prevention methods to be put in place. Contact tracing and monitoring is key to containing an outbreak. The definition of contacts is based on the risk profile. Successful management requires coordination by a team of multi-skilled senior persons who have the authority to make decisions. As with all critically ill patients, the participant experienced many emotions. The lack of ability to control situations and care appeared to be important. Feelings of guilt still remain. A different meaning of kindness was exposed. Infection prevention and isolation is part of routine nursing practice and should be applied if there is an index of suspicion of a contagious disease. Care of patients with VHF is not routinely taught however maintaining basic principles may prevent spread and thus further cases. Support of and communication with all staff in the hospital is important for commitment. The setting in this study was a hospital in the private sector. The revelations of this case study can be used in future research to develop guidelines for use by the outbreak management team. They are intended to improve the management and emotional support of the health care workers as well as the victims and can be applied to outbreaks of any nature.
Books on the topic "Arenaviridae Infections"
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Howard, Colin R. Arenaviruses. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198570028.003.0032.
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There are few groups of viral zoonoses that have attracted such widespread publicity as the arenaviruses, particularly during the 1960’s and 1970’s when Lassa emerged as a major cause of haemorrhagic disease in West Africa. More than any other zoonoses, members of the family are used extensively for the study of virus-host relationships. Thus the study of this unique group of enveloped, single-stranded RNA viruses has been pursued for two quite separate reasons. First, lymphocytic choriomeningitis virus (LCM) has been used as a model of persistent virus infections for over half a century; its study has contributed, and continues to contribute, a number of cardinal concepts to our present understanding of immunology. LCM virus remains the prototype of the Arenaviridae and is a common infection of laboratory mice, rats and hamsters. Once thought rare in humans there is now increasing evidence of LCM virus being implicated in renal disease and as a complication in organ transplantation. Second, certain arenaviruses cause severe haemorrhagic diseases in man, notably Lassa fever in Africa, Argentine and Bolivian haemorrhagic fevers in South America, Guaranito infection in Venezuela and Chaparé virus in Bolivia. The latter is a prime example for the need of ever-continuing vigilance for the emergence of new viral diseases; over the past few years several new arenaviruses have been reported as implicated with severe human disease and indeed the number of new arenaviruses discovered since the last edition of this book have increased the size of this virus family significantly.In common with LCM, the natural reservoir of these infections is a limited number of rodent species (Howard, 1986). Although the initial isolates from South America were at first erroneously designated as newly defined arboviruses, there is no evidence to implicate arthropod transmission for any arenavirus. However, similar methods of isolation and the necessity of trapping small animals have meant that the majority of arenaviruses have been isolated by workers in the arbovirus field. A good example of this is Guaranito virus that emerged during investigation of a dengue virus outbreak in Venezuela (Salas et al. 1991).There is an interesting spectrum of pathological processes among these viruses. All the evidence so far available suggests that the morbidity of Lassa fever and South American haemorrhagic fevers due to arenavirus infection results from the direct cytopathic action of these agents. This is in sharp contrast to the immunopathological basis of ‘classic’ lymphocytic choriomeningitis disease seen in adult mice infected with LCM virus and the use of this system for elucidating the phenomenon of H2-restriction of the host cytotoxic T cell response (Zinkernagel and Doherty 1979). Despite the utility of this experimental model for dissecting the nature of the immune response to virus infection and the growing interest in arenaviruses of rodents, there remains much to be done to elucidate the pathogenesis of these infections in humans.
Book chapters on the topic "Arenaviridae Infections"
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McCormick, Joseph B. "Arenaviridae: The Arenaviruses." In Laboratory Diagnosis of Infectious Diseases Principles and Practice, 647–62. New York, NY: Springer New York, 1988. http://dx.doi.org/10.1007/978-1-4612-3900-0_33.
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Thomsen, A. Randrup, and Charles J. Pfau. "Influence of Host Genes on the Outcome of Murine Lymphocytic Choriomeningitis Virus Infection." In The Arenaviridae, 199–224. Boston, MA: Springer US, 1993. http://dx.doi.org/10.1007/978-1-4615-3028-2_12.
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