Detection of Lassa Virus, Mali

Safronetz, David; López, Job E.; Sogoba, Nafomon; Traorè, Sékou F.; Raffel, Sandra J.; Fischer, Elizabeth R.; Ebihara, Hideki; Branco, Luis M.; Garry, Robert F.; Schwan, Tom G.; Feldmann, Heinz

doi:10.3201/eid1607.100146

Cited by 96 publications

(97 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These viruses are carried asymptomatically in wild rodents and are transmitted through contact with contaminated excretions. Endemic infection in these rodents maintains a reservoir of virus that can reemerge in human populations as outbreaks (1,18,30) or as novel pathogenic species (6). No FDA-licensed vaccines exist for these viruses, and current antiarenaviral therapy is limited to the off-label use of the nucleoside analogue ribavirin, which has had mixed success in treating cases of arenaviral hemorrhagic fever (HF) disease, while being associated with significant side effects (5).…”

mentioning

confidence: 99%

Conserved Residues in Lassa Fever Virus Z Protein Modulate Viral Infectivity at the Level of the Ribonucleoprotein

Capul

Torre

Buchmeier

2011

J Virol

View full text Add to dashboard Cite

Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a model for dissecting virus-host interactions in persistent and acute disease. The RING finger protein Z has been identified as the driving force of arenaviral budding and acts as the viral matrix protein. While residues in Z required for viral budding have been described, residues that govern the Z matrix function(s) have yet to be fully elucidated. Because this matrix function is integral to viral assembly, we reasoned that this would be reflected in sequence conservation. Using sequence alignment, we identified several conserved residues in Z outside the RING and late domains. Nine residues were each mutated to alanine in Lassa fever virus Z. All of the mutations affected the expression of an LCMV minigenome and the infectivity of virus-like particles, but to greatly varying degrees. Interestingly, no mutations appeared to affect Z-mediated budding or association with viral GP. Our findings provide direct experimental evidence supporting a role for Z in the modulation of the activity of the viral ribonucleoprotein (RNP) complex and its packaging into mature infectious viral particles.Arenaviruses are the causative agents of a number of human diseases, including lymphocytic choriomeningitis, Lassa fever, and Bolivian hemorrhagic fever. These viruses are carried asymptomatically in wild rodents and are transmitted through contact with contaminated excretions. Endemic infection in these rodents maintains a reservoir of virus that can reemerge in human populations as outbreaks (1,18,30) or as novel pathogenic species (6). No FDA-licensed vaccines exist for these viruses, and current antiarenaviral therapy is limited to the off-label use of the nucleoside analogue ribavirin, which has had mixed success in treating cases of arenaviral hemorrhagic fever (HF) disease, while being associated with significant side effects (5).The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is ubiquitous in wild rodents and can infect domesticated mice and hamsters. These infected hamsters have most recently been responsible for reported disease in humans (2, 34). Additionally, reports of transplant-associated LCMV disease and fatality highlight the clinical relevance of arenaviral infection in immunocompromised individuals (15). In addition, congenital transmission of LCMV has been implicated in a variety of clinical conditions that affect mainly the retina and brain (3, 4).Arenaviruses are enveloped viruses bearing a bi-segmented, negative-sense RNA genome. Each segment contains two open reading frames (ORFs) in the ambisense orientation that are separated by a noncoding intergenic region (IGR) and bounded at their 5Ј and 3Ј ends by untranslated regions (UTRs) that are critical for the control of viral R...

show abstract

mentioning

confidence: 99%

Conserved Residues in Lassa Fever Virus Z Protein Modulate Viral Infectivity at the Level of the Ribonucleoprotein

Capul

Torre

Buchmeier

2011

J Virol

View full text Add to dashboard Cite

show abstract

“…However, with highly diverse pathogens such as Lassa virus, genetic diversity can be problematic for nucleic acid-based assays, as even a single nucleotide variant in one of the primers can have a significant negative impact on assay sensitivity depending on the location of the nucleotide variant (43). Multiple real-time RT-PCR assays are published in the literature for Lassa virus (41,(44)(45)(46). For example, Safronetz and colleagues initially detected Lassa virus circulating in Mali using a SYBR green real-time RT-PCR assay targeting the Lassa virus S RNA segment (45), and Trombley and colleagues developed multiple probe-based Lassa virus assays due to strain diversity (44).…”

Section: Nucleic Acid Detection Methodsmentioning

confidence: 99%

“…Multiple real-time RT-PCR assays are published in the literature for Lassa virus (41,(44)(45)(46). For example, Safronetz and colleagues initially detected Lassa virus circulating in Mali using a SYBR green real-time RT-PCR assay targeting the Lassa virus S RNA segment (45), and Trombley and colleagues developed multiple probe-based Lassa virus assays due to strain diversity (44). However, standard RT-PCR assays are commonly used (28,29,46) due to their ease of use and the decreased specificity for probe-based real-time RT-PCR.…”

Section: Nucleic Acid Detection Methodsmentioning

confidence: 99%

Laboratory Diagnosis of Lassa Fever

Raabe

Koehler

2017

J Clin Microbiol

View full text Add to dashboard Cite

Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses.

show abstract

“…Low-passage (defined as Ͻ4 passages) LASV isolates Josiah (LASVJos) (10), Z-132 (LASVZ132) (11,12), and Soromba-R (LASVSor) (11), as well as LUJV, were cultured in Vero cells and titrated using standard methods for determining the median tissue culture infective dose (TCID 50 ).…”

Section: Methodsmentioning

confidence: 99%

Delayed Inflammatory and Cell Death Responses Are Associated with Reduced Pathogenicity in Lujo Virus-Infected Cynomolgus Macaques

Rasmussen

Tchitchek

Safronetz

et al. 2015

J Virol

Self Cite

View full text Add to dashboard Cite

To identify host factors associated with arenavirus virulence, we used a cynomolgus macaque model to evaluate the pathogenesis of Lujo virus (LUJV), a recently emerged arenavirus that caused an outbreak of severe viral hemorrhagic fever in southern Africa. In contrast to human cases, LUJV caused mild, nonlethal illness in macaques. We then compared this to contrasting clinical outcomes during arenavirus infection, specifically to samples obtained from macaques infected with three highly pathogenic lines of Lassa virus (LASV), the causative agent of Lassa fever (LF). We assessed gene expression in peripheral blood mononuclear cells (PBMC) and determined genes that significantly changed expression relative to that in uninfected animals over the course of infection. We detected a 72-h delay in the induction of host responses to infection during LUJV infection compared to that of the animals infected with LASV. This included genes associated with inflammatory and antiviral responses and was particularly apparent among groups of genes promoting cell death. We also observed early differential expression of a subset of genes specific to LUJV infection that accounts for the delayed inflammatory response. Cell type enrichment analysis suggested that host response induction delay and an LUJV-specific profile are due to a different proportion of natural killer cells responding in LUJV infection than that in the LASV-infected animals. Together, these data indicate that delayed proinflammatory and proapoptotic host responses to arenavirus infection could ameliorate disease severity. This conclusion provides insight into the cellular and molecular mechanisms of arenaviral hemorrhagic fever and suggests potential strategies for therapeutic development. IMPORTANCEOld World arenaviruses are significant human pathogens that often are associated with high mortality. However, mechanisms underlying disease severity and virulence in arenavirus hemorrhagic fever are largely unknown, particularly regarding host responses that contribute to pathogenicity. This study describes a comparison between Lujo and Lassa virus infection in cynomolgus macaques. Lujo virus-infected macaques developed only mild illness, while Lassa virus-infected macaques developed severe illness consistent with Lassa fever. We determined that mild disease is associated with a delay in host expression of genes linked to virulence, such as those causing inflammation and cell death, and with distinct cell types that may mediate this delay. This is the first study to associate the timing and directionality of gene expression with arenaviral pathogenicity and disease outcome and evokes new potential approaches for developing effective therapeutics for treating these deadly emerging pathogens. Since their discovery in the early 20th century, arenaviruses have been consistently associated with outbreaks of severe illness, including viral hemorrhagic fever (VHF) and encephalitis. Arenaviruses are bisegmented, ambisense, single-stranded, negative-sense RNA viruses t...

show abstract

Detection of Lassa Virus, Mali

Cited by 96 publications

References 10 publications

Conserved Residues in Lassa Fever Virus Z Protein Modulate Viral Infectivity at the Level of the Ribonucleoprotein

Conserved Residues in Lassa Fever Virus Z Protein Modulate Viral Infectivity at the Level of the Ribonucleoprotein

Laboratory Diagnosis of Lassa Fever

Delayed Inflammatory and Cell Death Responses Are Associated with Reduced Pathogenicity in Lujo Virus-Infected Cynomolgus Macaques

Contact Info

Product

Resources

About