Lassa fever diagnostics: past, present, and future

Happi, Anise N.; Happi, Christian; Schoepp, Randal J.

doi:10.1016/j.coviro.2019.08.002

Cited by 54 publications

(63 citation statements)

References 48 publications

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“…2). Lassa virus is the causative agent of the often fatal Lassa hemorrhagic fever and is prevalent only in Africa (reviewed in [68]); the GTEx samples were collected in the USA. We are unable to completely exclude the possibility that the GTEx samples positive for Lassa virus transcripts came from subjects asymptomatically infected with this virus.…”

Section: Discussionmentioning

confidence: 99%

A tissue level atlas of the healthy human virome

et al. 2020

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Background: Human-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the "virome") is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis. Results: To characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject's brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood. Conclusions: To our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.

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Section: Discussionmentioning

confidence: 99%

A tissue level atlas of the healthy human virome

et al. 2020

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“…Several mammarenaviruses, chiefly Lassa virus (LASV) in Western Africa and Junín virus (JUNV) in the Argentinian Pampas, can cause severe disease in humans (Lassa fever and Argentinian hemorrhagic fever, respectively), and pose important public health problems in their endemic regions. LASV is highly prevalent in Western Africa, where the virus infects hundreds of thousands of individuals yearly resulting in a high number of Lassa fever cases that are associated with high morbidity and a high case fatality rate among hospitalized patients [2]. Notably, increased travel has resulted in imported cases of Lassa fever into non-endemic metropolitan regions, including the United States (U.S.) [3,4].…”

Section: Introductionmentioning

confidence: 99%

Novel Dihydroorotate Dehydrogenase Inhibitors with Potent Interferon-Independent Antiviral Activity against Mammarenaviruses In Vitro

Kim

Cubitt

Caì

et al. 2020

Viruses

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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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“…Blood represents a complex matrix where the virus may be protected from damage that occurs during drying processes. Blood is also the basis for several Lassa virus diagnostic tests [ 16 , 17 ] and therefore was deemed to be a relevant and common sample type with which to investigate viral survival. The two temperatures selected for investigation represented indoor conditions (air conditioned laboratory) and an elevated temperature that represented the higher temperatures that might occur in West Africa [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Survival of Lassa Virus in Blood and Tissue Culture Media and in a Small Particle Aerosol

et al. 2020

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Knowledge of the survival and stability of a pathogen is important for understanding its risk, reducing its transmission, and establishing control measures. Lassa virus is endemic in West Africa, causes severe disease, and is an emerging pathogen of concern. Our study examined the survival of Lassa virus in blood and tissue culture media at two different temperatures. The stability of Lassa virus held within a small particle aerosol was also measured. In liquids, Lassa virus was found to decay more quickly at 30 °C compared to room temperature. Sealed samples protected from environmental desiccation were more stable than samples open to the environment. In a small particle aerosol, the decay rate of Lassa virus was determined at 2.69% per minute. This information can contribute to risk assessments and inform mitigation strategies in the event of an outbreak of Lassa virus.

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Lassa fever diagnostics: past, present, and future

Cited by 54 publications

References 48 publications

A tissue level atlas of the healthy human virome

A tissue level atlas of the healthy human virome

Novel Dihydroorotate Dehydrogenase Inhibitors with Potent Interferon-Independent Antiviral Activity against Mammarenaviruses In Vitro

Survival of Lassa Virus in Blood and Tissue Culture Media and in a Small Particle Aerosol

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