Lymphocytic choriomeningitis virus: Emerging fetal teratogen

Barton, Leslie L.; Mets, Marilyn B.; Beauchamp, Cynthia L.

doi:10.1067/mob.2002.126297

Cited by 153 publications

(131 citation statements)

References 3 publications

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“…Human transmission has been shown to occur in utero, upon transplantation with infected organs or upon contact with infected hamsters or laboratory animals (2)(3)(4). Congenital LCMV infection acts as an abortifacient and a fetal teratogen commonly manifested as chorioretinitis, hydrocephalus and microcephaly or macrocephaly (5)(6)(7)(8)(9). Adult infection with LCMV can lead to the development of fever, malaise, headaches, seizure and in some cases fatal meningitis (3,(10)(11)(12)(13).…”

Section: General Background On Lcmvmentioning

confidence: 99%

Lymphocytic choriomeningitis infection of the central nervous system

Kang

McGavern

2008

Front Biosci

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Viral infection of the central nervous system (CNS) can result in a multitude of responses including pathology, persistence or immune clearance. Lymphocytic choriomeningitis virus (LCMV) is a powerful model system to explore these potential outcomes of CNS infection due to the diversity of responses that can be achieved after viral inoculation. Several factors including tropism, timing, dose and variant of LCMV in combination with the development or suppression of the corresponding immune response dictates whether lethal meningitis, chronic infection or clearance of LCMV in the CNS will occur. Importantly, the functionality and positioning of the LCMV-specific CD8 + T cell response are critical in directing the subsequent outcome of CNS LCMV infection. Although a basic understanding of LCMV and immune interactions in the brain exists, the molecular machinery that shapes the balance between pathogenesis and clearance in the LCMV-infected CNS remains to be elucidated. This review covers the various outcomes of LCMV infection in the CNS and what is currently known about the impact of the virus itself versus the immune response in the development of disease or clearance. KeywordsLCMV; Clone 13; Virus; Meningitis; Immunotherapy; Brain; Neurons; Astrocytes; Immunodeficient; Neonates; Growth Hormone; T cell; behavior; Review INTRODUCTIONThe parameters that dictate pathology versus clearance after CNS viral infection are relatively undefined. The CNS contains highly integrated populations of neurons and glial cells responsible for our livelihood, and immune infiltration has the potential to severely disrupt the function of this sensitive compartment. Consequently, through evolutionary pressures the CNS has become immunologically specialized and now possesses the ability to HHS Public AccessAuthor manuscript Front Biosci. Author manuscript; available in PMC 2017 January 30.Published in final edited form as:Front Biosci. ; 13: 4529-4543. Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript modulate (or suppress) leukocyte behavior in a manner that fundamentally differs from that observed in most peripheral tissues. This evolutionary acquisition, which is advantageous from the standpoint of host survival, likely facilitates the entry and replication of viruses within the CNS. A multitude of viruses have the capacity to gain access to the CNS and upon doing so can establish a chronic infection, drive immunopathology, or alter the function of residents cells, making clearance of the invading pathogen essential. Therefore, a fundamental knowledge of viral-immune interactions in the CNS is essential if we ultimately intend to therapeutically modulate CNS immune responses in humans to achieve viral clearance in the absence of immunopathology. LCMV infection of mice provides an outstanding model system to explore such interactions and extend the lessons learned to virus infections of humans. GENERAL BACKGROUND ON LCMVLCMV is a natural pathogen of both human and murine populations (1). Human transmissio...

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Section: General Background On Lcmvmentioning

confidence: 99%

Lymphocytic choriomeningitis infection of the central nervous system

Kang

McGavern

2008

Front Biosci

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“…On the South American continent, the New World arenaviruses Junin (JUNV), Machupo, Guanarito, and Sabia viruses have emerged as causative agents of severe hemorrhagic fevers in Argentina, Bolivia, Venezuela, and Brazil, respectively (31). Moreover, compelling evidence indicates that the globally distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance, especially in cases of congenital infection leading to hydrocephalus, mental retardation, and chorioretinitis in infants (1,26). In addition, LCMV poses a special threat to immunocompromised individuals, as tragically illustrated by recent cases of transplant-associated infections by LCMV with fatal outcomes (11,28).…”

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confidence: 99%

Targeting the Proteolytic Processing of the Viral Glycoprotein Precursor Is a Promising Novel Antiviral Strategy against Arenaviruses

Rojek

Pasqual

Sánchez

et al. 2010

J Virol

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A crucial step in the arenavirus life cycle is the biosynthesis of the viral envelope glycoprotein (GP) responsible for virus attachment and entry. Processing of the GP precursor (GPC) by the cellular proprotein convertase site 1 protease (S1P), also known as subtilisin-kexin-isozyme 1 (SKI-1), is crucial for cell-to-cell propagation of infection and production of infectious virus. Here, we sought to evaluate arenavirus GPC processing by S1P as a target for antiviral therapy using a recently developed peptide-based S1P inhibitor, decanoyl (dec)-RRLL-chloromethylketone (CMK), and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). To control for off-target effects of dec-RRLL-CMK, we employed arenavirus reverse genetics to introduce a furin recognition site into the GPC of LCMV. The rescued mutant virus grew to normal titers, and the processing of its GPC critically depended on cellular furin, but not S1P.

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“…In addition, the recent identification of two novel HF-causing arenaviruses, Chapare virus in Bolivia (10) and Lujo virus in South Africa (11), has further reinforced concerns about the emergence of novel HF-causing arenaviruses. Additionally, evidence indicates that the lymphocytic choriomeningitis virus (LCMV) prototypic arenavirus, distributed worldwide, is a neglected human pathogen of clinical significance (12)(13)(14)(15). Besides their impact in human public health, arenaviruses pose also a credible biodefense threat, and six of them, including LCMV, LASV, and JUNV, are classified as NIAID category A agents (2,16).…”

mentioning

confidence: 99%

Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines

Cheng

Ortiz-Riaño

Torre

et al. 2015

J Virol

100

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Several members of the Arenaviridae family cause hemorrhagic fever disease in humans and pose serious public health problems in their geographic regions of endemicity as well as a credible biodefense threat. To date, there have been no FDA-approved arenavirus vaccines, and current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. Arenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome. Each genome segment uses an ambisense coding strategy to direct the synthesis of two viral polypeptides in opposite orientations, separated by a noncoding intergenic region. Here we have used minigenome-based approaches to evaluate expression levels of reporter genes from the nucleoprotein (NP) and glycoprotein precursor (GPC) loci within the S segment of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). We found that reporter genes are expressed to higher levels from the NP than from the GPC locus. Differences in reporter gene expression levels from the NP and GPC loci were confirmed with recombinant trisegmented LCM viruses. We then used reverse genetics to rescue a recombinant LCMV ( A renaviruses are enveloped viruses with a bisegmented negative-strand (NS) RNA genome that cause chronic infections of rodents across the world (1). Zoonotic transmission through either direct contact with contaminated material or inhalation of aerosolized particles can result in severe infection in humans (1). Several arenaviruses, mainly, Lassa virus (LASV), the agent responsible for Lassa fever (LF) in western Africa, and Junín virus (JUNV), the causative agent of Argentine hemorrhagic fever (AHF) in the Argentinean Pampas, cause severe HF diseases in humans that are associated with high morbidity and significant mortality, posing important health problems in their regions of endemicity (1-3). Importantly, increased travel has resulted in the importation of LF into nonendemic metropolitan regions around the globe, including the United States (4, 5), Europe (6), and Japan (7). Moreover, similarly to the situation recently illustrated with the 2014 Ebola virus outbreak in western Africa (8, 9), evidence indicates that regions of LASV endemicity are expanding. In addition, the recent identification of two novel HF-causing arenaviruses, Chapare virus in Bolivia (10) and Lujo virus in South Africa (11), has further reinforced concerns about the emergence of novel HF-causing arenaviruses. Additionally, evidence indicates that the lymphocytic choriomeningitis virus (LCMV) prototypic arenavirus, distributed worldwide, is a neglected human pathogen of clinical significance (12-15). Besides their impact in human public health, arenaviruses pose also a credible biodefense threat, and six of them, including LCMV, LASV, and JUNV, are classified as NIAID category A agents (2, 16). Threats posed by humanpathogenic arenaviruses are further aggravated by the lack of FDA-approved vaccines (1) and by current antiarenaviral therapy

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Lymphocytic choriomeningitis virus: Emerging fetal teratogen

Cited by 153 publications

References 3 publications

Lymphocytic choriomeningitis infection of the central nervous system

Lymphocytic choriomeningitis infection of the central nervous system

Targeting the Proteolytic Processing of the Viral Glycoprotein Precursor Is a Promising Novel Antiviral Strategy against Arenaviruses

Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines

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