Ecology of Lassa Virus

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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Designing a multi-epitope vaccine against the Lassa virus through reverse vaccinology, subtractive proteomics, and immunoinformatics approaches

Informatics in Medicine Unlocked ◽

10.1016/j.imu.2021.100683 ◽

2021 ◽

pp. 100683

Author(s):

Akinyemi Ademola Omoniyi ◽

Samuel Sunday Adebisi ◽

Sunday Abraham Musa ◽

James Oliver Nzalak ◽

Barnabas Danborno ◽

...

Keyword(s):

Reverse Vaccinology ◽

Lassa Virus ◽

Epitope Vaccine ◽

Subtractive Proteomics

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Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.0c11516 ◽

2021 ◽

Author(s):

Suyong Re ◽

Kenji Mizuguchi

Keyword(s):

Lassa Virus ◽

Antibody Epitopes

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Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles

Journal of Virology ◽

10.1128/jvi.01711-08 ◽

2009 ◽

Vol 83 (7) ◽

pp. 3228-3237 ◽

Cited By ~ 34

Author(s):

François-Loic Cosset ◽

Philippe Marianneau ◽

Geraldine Verney ◽

Fabrice Gallais ◽

Noel Tordo ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Cell Attachment ◽

Low Ph ◽

Cell Entry ◽

Lassa Virus ◽

Ph Optimum ◽

Humoral Immune

ABSTRACT The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.

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Identification of Protective Lassa Virus Epitopes That Are Restricted by HLA-A2

Journal of Virology ◽

10.1128/jvi.00896-06 ◽

2006 ◽

Vol 80 (17) ◽

pp. 8351-8361 ◽

Cited By ~ 44

Author(s):

Jason Botten ◽

Jeff Alexander ◽

Valerie Pasquetto ◽

John Sidney ◽

Polly Barrowman ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Sequence Data ◽

Recombinant Vaccinia Virus ◽

Target Cells ◽

Lassa Virus ◽

Primary Role ◽

Emerging Pathogens ◽

Glycoprotein Precursor ◽

Predictive Algorithm ◽

Positive Target

ABSTRACT Recovery from Lassa virus (LASV) infection usually precedes the appearance of neutralizing antibodies, indicating that cellular immunity plays a primary role in viral clearance. To date, the role of LASV-specific CD8+ T cells has not been evaluated in humans. To facilitate such studies, we utilized a predictive algorithm to identify candidate HLA-A2 supertype epitopes from the LASV nucleoprotein and glycoprotein precursor (GPC) genes. We identified three peptides (GPC42-50, GLVGLVTFL; GPC60-68, SLYKGVYEL; and GPC441-449, YLISIFLHL) that displayed high-affinity binding (≤98 nM) to HLA-A*0201, induced CD8+ T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LASV GPC in human HLA-A*0201-positive target cells. HLA-A*0201 mice immunized with either GPC42-50 or GPC60-68 were protected against challenge with a recombinant vaccinia virus that expressed LASV GPC. The epitopes identified in this study represent potential diagnostic reagents and candidates for inclusion in epitope-based vaccine constructs. Our approach is applicable to any pathogen with existing sequence data, does not require manipulation of the actual pathogen or access to immune human donors, and should therefore be generally applicable to category A through C agents and other emerging pathogens.

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