Pathogenicity and virulence mechanisms of Lassa virus and its animal modeling, diagnostic, prophylactic, and therapeutic developments

: Here, we summarized recent advances in laboratory and clinical research on gut microbiome. The goal is to highlight recent discoveries on the biology and behavioral manifestations of gut microbiomes under normal and pathologic conditions. With this new scientific knowledge, we wish to cultivate cross-fertilization of science across multi-disciplines in the hopes of exploiting the gut microbiome as a key component of human development and its dysbiosis may signal pathological alterations that can be therapeutically targeted for regenerative medicine. In the end, we identify innovative research avenues that will merit from collaborations across biomedical disciplines that may facilitate the development of gut microbiome-based biomarkers and therapeutics. Gut microbiome stands as a core research area that transcends pediatric and nursing care, cancer biology, neurodegenerative disorders, cardiac function and diseases, among many other basic science and clinical arenas.

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cccccImmunological screening of Lassa Virus among Health workers and Contacts of patients of Lassa fever in Ondo State

Immunobiology ◽

10.1016/j.imbio.2021.152076 ◽

2021 ◽

pp. 152076

Author(s):

Joseph Ojonugwa Shaibu ◽

Olumuyiwa Babalola Salu ◽

Olufemi Samuel Amoo ◽

Ifeoma Idigbe ◽

Adesola Zaidat Musa ◽

...

Keyword(s):

Health Workers ◽

Lassa Fever ◽

Lassa Virus ◽

Ondo State

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Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes

npj Genomic Medicine ◽

10.1038/s41525-021-00201-z ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Stetson Thacker ◽

Charis Eng

Keyword(s):

Autism Spectrum ◽

Pten Expression ◽

Differentially Expressed ◽

Risk Genes ◽

Animal Modeling ◽

Network Analyses ◽

Phosphorylated Proteins ◽

Mass Spectrometry Technology ◽

Neurological Processes

AbstractPTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential insight into ASD pathogenesis. Subsequently, we comprehensively characterized the neural (phospho)proteome of Ptenm3m4/m3m4 mice, which exhibits cytoplasmic-predominant Pten expression, by applying mass spectrometry technology to their brains at two-weeks- (P14) and six-weeks-of-age (P40). The differentially expressed/phosphorylated proteins were subjected to gene enrichment, pathway, and network analyses to assess the affected biology. We identified numerous differentially expressed/phosphorylated proteins, finding greater dysregulation at P40 consistent with prior transcriptomic data. The affected pathways were largely related to PTEN function or neurological processes, while scant direct overlap was found across datasets. Network analysis pointed to ASD risk genes like Pten and Psd-95 as major regulatory hubs, suggesting they likely contribute to initiation or maintenance of cellular and perhaps organismal phenotypes related to ASD.

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Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

Viruses ◽

10.3390/v13050851 ◽

2021 ◽

Vol 13 (5) ◽

pp. 851

Author(s):

Chris Hoffmann ◽

Stephanie Wurr ◽

Elisa Pallasch ◽

Sabrina Bockholt ◽

Toni Rieger ◽

...

Keyword(s):

Persistent Infection ◽

Virus Transmission ◽

Host Population ◽

Natural Host ◽

Lassa Virus ◽

Mastomys Natalensis ◽

Natural Hosts ◽

History Of ◽

Morogoro Virus ◽

The Impact

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population.

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Lassa Virus Circulation in Small Mammal Populations in Bo District, Sierra Leone

Biology ◽

10.3390/biology10010028 ◽

2021 ◽

Vol 10 (1) ◽

pp. 28

Author(s):

Umaru Bangura ◽

Jacob Buanie ◽

Joyce Lamin ◽

Christopher Davis ◽

Gédéon Ngiala Bongo ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Sierra Leone ◽

Small Mammal ◽

Hemorrhagic Fever ◽

Lassa Fever ◽

Lassa Virus ◽

Sierra Leonean ◽

Bayesian Phylogenetic Analysis ◽

Prevalent Species ◽

Lineage Iv

Lassa fever is a viral hemorrhagic fever caused by the Lassa virus LASV, which was first isolated in the rodent Mastomys natalensis in 1974 in Kenema, Sierra Leone. As little is known about the abundance and the presence of LASV in rodents living in the Bo area, we carried out a small mammal longitudinal population survey. A standardized trapping session was performed in various habitats and seasons in six villages over two years (2014–2016) and samples collected were tested for arenavirus IgG and LASV. A Bayesian phylogenetic analysis was performed on sequences identified by PCR. A total of 1490 small mammals were collected, and 16 rodent species were identified, with M. natalensis (355, 24%) found to be the most prevalent species. Forty-one (2.8%) samples were IgG positive, and 31 of these were trapped in homes and 10 in surrounding vegetation. Twenty-nine of 41 seropositive rodents were M. natalensis. We detected four LASV by PCR in two villages, all found in M. natalensis. Phylogenetic analysis showed that the sequences were distributed within the Sierra Leonean clade within lineage IV, distinguishing a Bo sub-clade older than a Kenema sub-clade. Compared to other settings, we found a low abundance of M. natalensis and a low circulation of LASV in rodents in villages around Bo district.

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