scholarly journals Phylogenetic and Mutational Analysis of Lassa Virus Strains Isolated in Nigeria: Proposal for an In Silico Study

10.2196/23015 ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. e23015
Author(s):  
Daniel Kolawole ◽  
Hayatu Raji ◽  
Malachy Ifeanyi Okeke
Keyword(s):  
Phylogenetic Trees ◽  
Mutational Analysis ◽  
Current Knowledge ◽  
Marker Gene ◽  
Lassa Fever ◽  
Reference Sequence ◽  
Lassa Virus ◽  
Viral Marker ◽  
Virus Isolates ◽  
Virus Strains

Background In 2018, the total number of Lassa fever cases in Nigeria was significantly higher than that observed in previous years. Hence, studies had attempted to determine the underlying cause. However, reports using phylogenetic methods to analyze this finding ruled out the emergence of potentially more transmissible Lassa virus strains or an increase in human-to-human viral transmission as the cause underlying the increase in cases. Two years later, the situation seems even worse as the number of confirmed cases has reached an all-time high according to situational reports released by the Nigerian Center for Disease Control. Objective Considering the increasing trend of Lassa fever cases and related mortality, the major objective of this study is to map mutations within the genomes of Lassa virus isolates from 2018 and 2019 using the reference sequence available at the National Center for Biotechnology Information as a benchmark and compare them to the genomes of viruses isolated during 1969-2017. This study would also attempt to identify a viral marker gene for easier identification and grouping. Finally, the time-scaled evolution of Lassa virus in Nigeria will be reconstructed. Methods After collecting the sequence data of Lassa virus isolates, Bayesian phylogenetic trees, a sequence identity matrix, and a single nucleotide polymorphism matrix will be generated using BEAST (version 2.6.2), Base-By-Base, and DIVEIN (a web-based tool for variant calling), respectively. Results Mining and alignment of Lassa virus genome sequences have been completed, while mutational analysis and the reconstruction of time-scaled maximum clade credibility trees, congruence tests for inferred segments, and gene phylogeny analysis are ongoing. Conclusions The findings of this study would further the current knowledge of the evolutionary history of the Lassa virus in Nigeria and would document the mutations in Nigerian isolates from 1969 to 2019. International Registered Report Identifier (IRRID) DERR1-10.2196/23015

scholarly journals Phylogenetic and Mutational Analysis of Lassa Virus Strains Isolated in Nigeria: Proposal for an In Silico Study (Preprint)

2020 ◽  
Author(s):  
Daniel Kolawole ◽  
Hayatu Raji ◽  
Malachy Ifeanyi Okeke
Keyword(s):  
Phylogenetic Trees ◽  
Mutational Analysis ◽  
Current Knowledge ◽  
Marker Gene ◽  
Lassa Fever ◽  
Reference Sequence ◽  
Lassa Virus ◽  
Viral Marker ◽  
Virus Isolates ◽  
Virus Strains

BACKGROUND In 2018, the total number of Lassa fever cases in Nigeria was significantly higher than that observed in previous years. Hence, studies had attempted to determine the underlying cause. However, reports using phylogenetic methods to analyze this finding ruled out the emergence of potentially more transmissible Lassa virus strains or an increase in human-to-human viral transmission as the cause underlying the increase in cases. Two years later, the situation seems even worse as the number of confirmed cases has reached an all-time high according to situational reports released by the Nigerian Center for Disease Control. OBJECTIVE Considering the increasing trend of Lassa fever cases and related mortality, the major objective of this study is to map mutations within the genomes of Lassa virus isolates from 2018 and 2019 using the reference sequence available at the National Center for Biotechnology Information as a benchmark and compare them to the genomes of viruses isolated during 1969-2017. This study would also attempt to identify a viral marker gene for easier identification and grouping. Finally, the time-scaled evolution of Lassa virus in Nigeria will be reconstructed. METHODS After collecting the sequence data of Lassa virus isolates, Bayesian phylogenetic trees, a sequence identity matrix, and a single nucleotide polymorphism matrix will be generated using BEAST (version 2.6.2), Base-By-Base, and DIVEIN (a web-based tool for variant calling), respectively. RESULTS Mining and alignment of Lassa virus genome sequences have been completed, while mutational analysis and the reconstruction of time-scaled maximum clade credibility trees, congruence tests for inferred segments, and gene phylogeny analysis are ongoing. CONCLUSIONS The findings of this study would further the current knowledge of the evolutionary history of the Lassa virus in Nigeria and would document the mutations in Nigerian isolates from 1969 to 2019. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/23015

scholarly journals Phylogeography of Lassa Virus in Nigeria

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Deborah U. Ehichioya ◽  
Simon Dellicour ◽  
Meike Pahlmann ◽  
Toni Rieger ◽  
Lisa Oestereich ◽  
...  
Keyword(s):  
West Africa ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Future Research ◽  
Lassa Virus ◽  
Southeastern Part ◽  
Data Set ◽  
Content Type ◽  
Virus Strains

ABSTRACT Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatiotemporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian states. The final data set, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 states. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while a few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi. Within lineages II and III, seven and five sublineages, respectively, were distinguishable. Phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal toward the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast toward Taraba and Adamawa and south toward Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sublineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at a higher resolution. In addition, we estimated the direction and time frame of virus dispersal in the country. IMPORTANCE Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sublineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows us to predict into which geographical areas the virus might spread in the future and prioritize areas for Lassa fever surveillance. Our study not only aimed to generate Lassa virus sequences from across Nigeria but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.

scholarly journals Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus

2004 ◽  
Vol 78 (6) ◽  
pp. 3162-3169 ◽  
Author(s):  
Marcel Asper ◽  
Thomas Sternsdorf ◽  
Meike Hass ◽  
Christian Drosten ◽  
Antje Rhode ◽  
...  
Keyword(s):  
Vero Cells ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
High Pathogenicity ◽  
Ifn Γ ◽  
Virus Strains

ABSTRACT The high pathogenicity of Lassa virus is assumed to involve resistance to the effects of interferon (IFN). We have analyzed the effects of alpha IFN (IFN-α), IFN-γ, and tumor necrosis factor alpha (TNF-α) on replication of Lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (LCMV). Three low-passage Lassa virus strains (AV, NL, and CSF), isolated from humans with mild to fulminant Lassa fever, were tested. Lassa virus replication was inhibited by IFN-α and IFN-γ, but not TNF-α, in Huh7 and Vero cells. The degree of IFN sensitivity of a Lassa virus isolate did not correlate with disease severity in human patients. Furthermore, cytokine effects observed for Lassa virus and LCMV (strains CH-5692, Armstrong, and WE) were similar. To address the mechanisms involved in the IFN effect, we used cell lines in which overexpression of IFN-stimulated proteins promyelocytic leukemia protein (PML) and Sp100 could be induced. Both proteins reside in PML bodies, a cellular target of the LCMV and Lassa virus Z proteins. Overexpression of PML or Sp100 did not affect replication of either virus. This, together with the previous finding that PML knockout facilitates LCMV replication in vitro and in vivo (M. Djavani, J. Rodas, I. S. Lukashevich, D. Horejsh, P. P. Pandolfi, K. L. Borden, and M. S. Salvato, J. Virol. 75:6204-6208, 2001; W. V. Bonilla, D. D. Pinschewer, P. Klenerman, V. Rousson, M. Gaboli, P. P. Pandolfi, R. M. Zinkernagel, M. S. Salvato, and H. Hengartner, J. Virol. 76:3810-3818, 2002), describes PML as a mediator within the antiviral pathway rather than as a direct effector protein. In conclusion, the high pathogenicity of Lassa virus compared to LCMV is probably not due to increased resistance to the effects of IFN-α or IFN-γ. Both cytokines inhibit replication which is relevant for the design of antiviral strategies against Lassa fever with the aim of enhancing the IFN response.

Endemic Lassa fever in Liberia. III. Characterization of Lassa virus isolates

1985 ◽  
Vol 79 (3) ◽  
pp. 374-379 ◽  
Author(s):  
Peter B. Jahrling ◽  
John D. Frame ◽  
Sheilda B. Smith ◽  
Mark H. Monson
Keyword(s):  
Lassa Fever ◽  
Lassa Virus ◽  
Virus Isolates

scholarly journals Identification of a Novel Consensus Sequence at the Cleavage Site of the Lassa Virus Glycoprotein

2000 ◽  
Vol 74 (23) ◽  
pp. 11418-11421 ◽  
Author(s):  
Oliver Lenz ◽  
Jan ter Meulen ◽  
Heinz Feldmann ◽  
Hans-Dieter Klenk ◽  
Wolfgang Garten
Keyword(s):  
Mutational Analysis ◽  
Consensus Sequence ◽  
Peptide Bond ◽  
Lassa Virus ◽  
Virus Glycoprotein ◽  
Amino Terminal ◽  
Viral Glycoproteins ◽  
Carboxy Terminal ◽  
Cleavage Motif ◽  
Virus Isolates

ABSTRACT The Lassa virus glycoprotein consists of an amino-terminal and a carboxy-terminal cleavage fragment designated GP-1 and GP-2, respectively, that are derived by proteolysis from the precursor GP-C. The membrane-anchored GP-2 obtained from purified virions of the Josiah strain revealed the N-terminal tripeptide GTF262 when analyzed by Edman degradation. Upstream of this site, GP-C contains the tetrapeptide sequence RRLL259, which is conserved in all Lassa virus isolates published to date. Systematic mutational analysis of vector-expressed GP-C revealed that the motif R-X (L/I/V)-L259 (where X stands for L, I, or V) is essential for cleavage of the peptide bond between leucine259 and glycine260. This cleavage motif is homologous to the consensus sequence recognized by a novel class of cellular endoproteases which have so far not been implicated in the processing of viral glycoproteins.

The identification of a novel HIV-1 second-generation recombinant form (CRF01_AE/CRF07_BC) among men who have sex with men in Jiangsu, China

2020 ◽  
Vol 18 ◽  
Author(s):  
Yin Yueqi ◽  
Zhou Ying ◽  
Lu Jing ◽  
Guo Hongxiong ◽  
Chen Jianshuang ◽  
...  
Keyword(s):  
Maximum Likelihood ◽  
Phylogenetic Trees ◽  
Second Generation ◽  
Emergency Situation ◽  
The World ◽  
Break Points ◽  
Sex With Men ◽  
Full Length Genome ◽  
Virus Strains ◽  
Hiv 1

Background: CRF01_AE and CRF07_BC are the two major HIV-1 virus strains circulating in China. The proportion of dominant subtypes (CRF01_AE and CRF07_BC) among MSM in Jiangsu province was over 80%. A large number of URFs have been found in China in recently years. Objective: This study aimed to report on novel HIV-1 recombinants. Method: We constructed Phylogenetic trees using the maximum likelihood (ML) method with 1000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination break points using SimPlot 3.5.1. Results: We identified a novel, second-generation HIV-1 recombinant (JS020202) between CRF01_AE and CRF07_BC. The analysis of near full-length genome (NFLG) showed there were at least 8 breakpoints inner virus, which differed from any previously identified CRF and URF around the world. Conclusion: Novel diverse CRF01_AE/07_BC suggested the complexity trends of HIV-1 genetics. The emergency situation of diverse recombinant strains should be monitored continuously.

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

Immunobiology ◽  
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

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

Biology ◽  
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.

scholarly journals Analysis of SARS-CoV-2 nucleocapsid protein sequence variations in ASEAN countries

2021 ◽  
Author(s):  
Mochammad Rajasa Mukti Negara ◽  
Ita Krissanti ◽  
Gita Widya Pradini
Keyword(s):  
Phylogenetic Tree ◽  
Phylogenetic Trees ◽  
Protein Sequences ◽  
Reference Sequence ◽  
N Protein ◽  
Asean Country ◽  
Sequence Variations ◽  
Complete Sequences ◽  
Asean Countries ◽  
Global Initiative

BACKGROUND Nucleocapsid (N) protein is one of four structural proteins of SARS-CoV-2  which is known to be more conserved than spike protein and is highly immunogenic. This study aimed to analyze the variation of the SARS-CoV-2 N protein sequences in ASEAN countries, including Indonesia. METHODS Complete sequences of SARS-CoV-2 N protein from each ASEAN country were obtained from Global Initiative on Sharing All Influenza Data (GISAID), while the reference sequence was obtained from GenBank. All sequences collected from December 2019 to March 2021 were grouped to the clade according to GISAID, and two representative isolates were chosen from each clade for the analysis. The sequences were aligned by MUSCLE, and phylogenetic trees were built using MEGA-X software based on the nucleotide and translated AA sequences. RESULTS 98 isolates of complete N protein genes from ASEAN countries were analyzed. The nucleotides of all isolates were 97.5% conserved. Of 31 nucleotide changes, 22 led to amino acid (AA) substitutions; thus, the AA sequences were 94.5% conserved. The phylogenetic tree of nucleotide and AA sequences shows similar branches. Nucleotide variations in clade O (C28311T); clade GR (28881–28883 GGG>AAC); and clade GRY (28881–28883 GGG>AAC and C28977T) lead to specific branches corresponding to the clade within both trees. CONCLUSIONS The N protein sequences of SARS-CoV-2 across ASEAN countries are highly conserved. Most isolates were closely related to the reference sequence originating from China, except the isolates representing clade O, GR, and GRY which formed specific branches in the phylogenetic tree.

scholarly journals Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates

2021 ◽  
Vol 17 (10) ◽  
pp. e1009966
Author(s):  
Derek R. Stein ◽  
Bryce M. Warner ◽  
Jonathan Audet ◽  
Geoff Soule ◽  
Vinayakumar Siragam ◽  
...  
Keyword(s):  
Animal Models ◽  
Lassa Fever ◽  
Geographic Region ◽  
World Health ◽  
Limiting Factor ◽  
Lassa Virus ◽  
African Countries ◽  
Animal Models Of Disease ◽  
Medical Countermeasures

Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.

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