scholarly journals Virus–Host Interactions Involved in Lassa Virus Entry and Genome Replication

Pathogens ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 17 ◽  
Author(s):  
María Loureiro ◽  
Alejandra D’Antuono ◽  
Nora López
Keyword(s):  
Rational Design ◽  
Virus Entry ◽  
Lassa Fever ◽  
Hemorrhagic Disease ◽  
Lassa Virus ◽  
Genome Replication ◽  
Host Proteins ◽  
Mortality And Morbidity ◽  
Host Interactions ◽  
Cellular Factors

Lassa virus (LASV) is the causative agent of Lassa fever, a human hemorrhagic disease associated with high mortality and morbidity rates, particularly prevalent in West Africa. Over the past few years, a significant amount of novel information has been provided on cellular factors that are determinant elements playing a role in arenavirus multiplication. In this review, we focus on host proteins that intersect with the initial steps of the LASV replication cycle: virus entry and genome replication. A better understanding of relevant virus–host interactions essential for sustaining these critical steps may help to identify possible targets for the rational design of novel therapeutic approaches against LASV and other arenaviruses that cause severe human disease.

scholarly journals CP100356 Hydrochloride, a P-Glycoprotein Inhibitor, Inhibits Lassa Virus Entry: Implication of a Candidate Pan-Mammarenavirus Entry Inhibitor

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1763
Author(s):  
Toru Takenaga ◽  
Zihan Zhang ◽  
Yukiko Muramoto ◽  
Sarah Katharina Fehling ◽  
Ai Hirabayashi ◽  
...  
Keyword(s):  
Virus Entry ◽  
Lassa Fever ◽  
Lymphocytic Choriomeningitis ◽  
Entry Inhibitor ◽  
Lassa Virus ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Vesicular Stomatitis ◽  
Approved Drugs

Lassa virus (LASV)—a member of the family Arenaviridae—causes Lassa fever in humans and is endemic in West Africa. Currently, no approved drugs are available. We screened 2480 small compounds for their potential antiviral activity using pseudotyped vesicular stomatitis virus harboring the LASV glycoprotein (VSV-LASVGP) and a related prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). Follow-up studies confirmed that CP100356 hydrochloride (CP100356), a specific P-glycoprotein (P-gp) inhibitor, suppressed VSV-LASVGP, LCMV, and LASV infection with half maximal inhibitory concentrations of 0.52, 0.54, and 0.062 μM, respectively, without significant cytotoxicity. Although CP100356 did not block receptor binding at the cell surface, it inhibited low-pH-dependent membrane fusion mediated by arenavirus glycoproteins. P-gp downregulation did not cause a significant reduction in either VSV-LASVGP or LCMV infection, suggesting that P-gp itself is unlikely to be involved in arenavirus entry. Finally, our data also indicate that CP100356 inhibits the infection by other mammarenaviruses. Thus, our findings suggest that CP100356 can be considered as an effective virus entry inhibitor for LASV and other highly pathogenic mammarenaviruses.

scholarly journals Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Megan L. Heinrich ◽  
Matthew L. Boisen ◽  
Diana K. S. Nelson ◽  
Duane J. Bush ◽  
Robert W. Cross ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Vaccine Development ◽  
Natural Infection ◽  
Development Program ◽  
Lassa Fever ◽  
Cross Reactivity ◽  
Hemorrhagic Disease ◽  
Lassa Virus ◽  
Human Immune System ◽  
Sierra Leonean

Abstract Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI’s (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II–IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.

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 Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 448
Author(s):  
Sineewanlaya Wichit ◽  
Nuttamonpat Gumpangseth ◽  
Rodolphe Hamel ◽  
Sakda Yainoy ◽  
Siwaret Arikit ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Antiviral Agent ◽  
Viral Proteins ◽  
Targeted Therapeutics ◽  
Limited Information ◽  
Mosquito Vectors ◽  
Host Proteins ◽  
Host Interactions ◽  
Viral Host Interactions

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

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 Viruses go modular

2020 ◽  
Vol 295 (14) ◽  
pp. 4604-4616 ◽  
Author(s):  
Ariel Shepley-McTaggart ◽  
Hao Fan ◽  
Marius Sudol ◽  
Ronald N. Harty
Keyword(s):  
Hippo Pathway ◽  
Host Proteins ◽  
Dna Viruses ◽  
Ww Domain ◽  
Ww Domains ◽  
Host Interactions ◽  
New Class ◽  
Domain Interactions ◽  
Molecular Aspects ◽  
The Hippo Pathway

The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics.

Lassa hemorrhagic fever model using new generalized Caputo-type fractional derivative operator

2021 ◽  
pp. 2150055
Author(s):  
Pushpendra Kumar ◽  
Vedat Suat Erturk ◽  
Abdullahi Yusuf ◽  
Tukur Abdulkadir Sulaiman
Keyword(s):  
Pregnant Women ◽  
Fractional Order ◽  
Research Work ◽  
Hemorrhagic Fever ◽  
Hemorrhagic Disease ◽  
Lassa Virus ◽  
Research Fields ◽  
Negative Impacts ◽  
Predictor Corrector ◽  
The Given

In some of the previous decades, we have observed that mathematical modeling has become one of the most interesting research fields and has attracted many researchers. In this regard, thousands of researchers have proposed different varieties of mathematical models to study the dynamics of a number of real-world problems. This research work is framed to analyzing the structure of the well-known Lassa hemorrhagic epidemic; a dangerous epidemic for pregnant women, via new generalized Caputo type noninteger order derivative with the help of a modified Predictor–Corrector scheme. Lassa hemorrhagic disease is an epidemical and biocidal fever, whose negative impacts were initially recognized in the countries of Africa. This virus has killed many pregnant women as compared to the Ebola epidemic. It was noticed that Lassa virus was isolated in Vero cell cultures from a blood pattern, and after 12 days it was ejective, after the climb of the sickness. In this research study, necessary theorems and lemmas are reminded to prove the existence of a unique solution and stability of given fractional approximation scheme. All necessary results are reminded to confirm the effectiveness of the proposed approximation algorithm by graphical observations for various fractional-order values. In our practical calculations, we plotted the graphs for two different values of natural death rate along with various values of given fractional-order operator. Our major target is to show the importance of the proposed modified version of the Predictor–Corrector algorithm in epidemic studies by exploring the given Lassa hemorrhagic fever dynamics.

scholarly journals Unleashing the Full Potential of Oncolytic Adenoviruses against Cancer by Applying RNA Interference: The Force Awakens

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 228 ◽  
Author(s):  
Tereza Brachtlova ◽  
Victor van Beusechem
Keyword(s):  
Rna Interference ◽  
Immune Responses ◽  
Oncolytic Viruses ◽  
Full Potential ◽  
Anticancer Efficacy ◽  
Host Interactions ◽  
Oncolytic Adenoviruses ◽  
Cellular Factors ◽  
Immunotherapy Of Cancer ◽  
Cellular Pathways

Oncolytic virus therapy of cancer is an actively pursued field of research. Viruses that were once considered as pathogens threatening the wellbeing of humans and animals alike are with every passing decade more prominently regarded as vehicles for genetic and oncolytic therapies. Oncolytic viruses kill cancer cells, sparing healthy tissues, and provoke an anticancer immune response. Among these viruses, recombinant adenoviruses are particularly attractive agents for oncolytic immunotherapy of cancer. Different approaches are currently examined to maximize their therapeutic effect. Here, knowledge of virus–host interactions may lead the way. In this regard, viral and host microRNAs are of particular interest. In addition, cellular factors inhibiting viral replication or dampening immune responses are being discovered. Therefore, applying RNA interference is an attractive approach to strengthen the anticancer efficacy of oncolytic viruses gaining attention in recent years. RNA interference can be used to fortify the virus’ cancer cell-killing and immune-stimulating properties and to suppress cellular pathways to cripple the tumor. In this review, we discuss different ways of how RNA interference may be utilized to increase the efficacy of oncolytic adenoviruses, to reveal their full potential.

scholarly journals Bacteria Use Structural Imperfect Mimicry To Hijack The Host Interactome

2020 ◽  
Author(s):  
Natalia Sanchez de Groot ◽  
Marc Torrent Burgas
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Eukaryotic Proteins ◽  
Host Pathogen ◽  
Imperfect Mimicry ◽  
The Way

ABSTRACTBacteria use protein-protein interactions to infect their hosts and hijack fundamental pathways, which ensures their survival and proliferation. Hence, the infectious capacity of the pathogen is closely related to its ability to interact with host proteins. Here, we show that hubs in the host-pathogen interactome are isolated in the pathogen network by adapting the geometry of the interacting interfaces. An imperfect mimicry of the eukaryotic interfaces allows pathogen proteins to actively bind to the host’s target while preventing deleterious effects on the pathogen interactome. Understanding how bacteria recognize eukaryotic proteins may pave the way for the rational design of new antibiotic molecules.

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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