scholarly journals Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain Is Essential for Attenuation of Enterovirus 71 in the NOD/SCID Mouse Infection Model

2007 ◽  
Vol 82 (4) ◽  
pp. 1787-1797 ◽  
Author(s):  
Minetaro Arita ◽  
Yasushi Ami ◽  
Takaji Wakita ◽  
Hiroyuki Shimizu
Keyword(s):  
Scid Mouse ◽  
Enterovirus 71 ◽  
Cooperative Effect ◽  
Scid Mice ◽  
Infection Model ◽  
Single Mutation ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
Ev71 Strain ◽  
Nontranslated Region

ABSTRACT Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3′)] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5′ nontranslated region (NTR), 3D polymerase, and 3′ NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3′ NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

scholarly journals Seroprevalence of toxoplasmosis among reproductive-aged women in Myanmar and evaluation of luciferase immunoprecipitation system assay

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khin Myo Aye ◽  
Eiji Nagayasu ◽  
Myat Htut Nyunt ◽  
Ni Ni Zaw ◽  
Kyaw Zin Thant ◽  
...  
Keyword(s):  
Rural Communities ◽  
Toxoplasma Gondii ◽  
Infection Model ◽  
Reference Test ◽  
Serum Samples ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
Younger Age ◽  
Low Sensitivity ◽  
Reproductive Aged Women

Abstract Backgrounds Primary infection with Toxoplasma gondii during pregnancy can pose serious health problems for the fetus. However, the epidemiological status of toxoplasmosis among reproductive-aged population in Myanmar is largely unknown. Although luciferase immunoprecipitation system (LIPS) assays for serodiagnosis of toxoplasmosis was developed mostly using mouse infection model, had not been tested by using field-derived human samples. Methods A total of 251 serum samples were collected from reproductive-aged women, residing in Shwegyin township, Bago region, Myanmar and analyzed with a commercial ELISA kit, as well as in-house LIPS assays. Results The overall seroprevalence for Toxoplasma gondii infection by the commercial ELISA was 11.5%. No clear risk factor was identified except for being in the younger age group (15–30 years old). Overall, LIPS assays showed low sensitivity when the commercial ELSA was used as a reference test. Conclusion We identified the epidemiological situation of toxoplasmosis in some rural communities in Myanmar. The data obtained here will serve as a primary information for the effort to reduce toxoplasmosis in this region. Although looked promising in the previous experiments with mouse infection model, we found that the reported LIPS procedures need further improvements to increase the sensitivities.

scholarly journals Phenotypic and Molecular Biological Analysis of Polymycovirus AfuPmV-1M From Aspergillus fumigatus: Reduced Fungal Virulence in a Mouse Infection Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Azusa Takahashi-Nakaguchi ◽  
Erika Shishido ◽  
Misa Yahara ◽  
Syun-ichi Urayama ◽  
Akihiro Ninomiya ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Sequence Similarity ◽  
Infection Model ◽  
Dsrna Segment ◽  
High Sequence Similarity ◽  
Fungal Virulence ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
Macrophage Phagocytosis ◽  
Free Strain

The filamentous fungal pathogen Aspergillus fumigatus is one of the most common causal agents of invasive fungal infection in humans; the infection is associated with an alarmingly high mortality rate. In this study, we investigated whether a mycovirus, named AfuPmV-1M, can reduce the virulence of A. fumigatus in a mouse infection model. AfuPmV-1M has high sequence similarity to AfuPmV-1, one of the polymycovirus that is a capsidless four-segment double-stranded RNA (dsRNA) virus, previously isolated from the genome reference strain of A. fumigatus, Af293. However, we found the isolate had an additional fifth dsRNA segment, referred to as open reading frame 5 (ORF5), which has not been reported in AfuPmV-1. We then established isogenic lines of virus-infected and virus-free A. fumigatus strains. Mycovirus infection had apparent influences on fungal phenotypes, with the virus-infected strain producing a reduced mycelial mass and reduced conidial number in comparison with these features of the virus-free strain. Also, resting conidia of the infected strain showed reduced adherence to pulmonary epithelial cells and reduced tolerance to macrophage phagocytosis. In an immunosuppressed mouse infection model, the virus-infected strain showed reduced mortality in comparison with mortality due to the virus-free strain. RNA sequencing and high-performance liquid chromatography (HPLC) analysis showed that the virus suppressed the expression of genes for gliotoxin synthesis and its production at the mycelial stage. Conversely, the virus enhanced gene expression and biosynthesis of fumagillin. Viral RNA expression was enhanced during conidial maturation, conidial germination, and the mycelial stage. We presume that the RNA or translation products of the virus affected fungal phenotypes, including spore formation and toxin synthesis. To identify the mycovirus genes responsible for attenuation of fungal virulence, each viral ORF was ectopically expressed in the virus-free KU strain. We found that the expression of ORF2 and ORF5 reduced fungal virulence in the mouse model. In addition, ORF3 affected the stress tolerance of host A. fumigatus in culture. We hypothesize that the respective viral genes work cooperatively to suppress the pathogenicity of the fungal host.

scholarly journals Methionyl-tRNA synthetase inhibitor has potent in vivo activity in a novel Giardia lamblia luciferase murine infection model

2020 ◽  
Vol 75 (5) ◽  
pp. 1218-1227
Author(s):  
Samantha A Michaels ◽  
Han-Wei Shih ◽  
Bailin Zhang ◽  
Edelmar D Navaluna ◽  
Zhongsheng Zhang ◽  
...  
Keyword(s):  
Giardia Lamblia ◽  
Trna Synthetase ◽  
Luciferase Reporter ◽  
Infection Model ◽  
Cell Assay ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
Methionyl Trna Synthetase

Abstract Background Methionyl-tRNA synthetase (MetRS) inhibitors are under investigation for the treatment of intestinal infections caused by Giardia lamblia. Objectives To properly analyse the therapeutic potential of the MetRS inhibitor 1717, experimental tools including a robust cell-based assay and a murine model of infection were developed based on novel strains of G. lamblia that employ luciferase reporter systems to quantify viable parasites. Methods Systematic screening of Giardia-specific promoters and luciferase variants led to the development of a strain expressing the click beetle green luciferase. Further modifying this strain to express NanoLuc created a dual reporter strain capable of quantifying parasites in both the trophozoite and cyst stages. These strains were used to develop a high-throughput cell assay and a mouse infection model. A library of MetRS inhibitors was screened in the cell assay and Compound-1717 was tested for efficacy in the mouse infection model. Results Cell viability in in vitro compound screens was quantified via bioluminescence readouts while infection loads in mice were monitored with non-invasive whole-animal imaging and faecal analysis. Compound-1717 was effective in clearing mice of Giardia infection in 3 days at varying doses, which was supported by data from enzymatic and phenotypic cell assays. Conclusions The new in vitro and in vivo assays based on luciferase expression by engineered G. lamblia strains are useful for the discovery and development of new therapeutics for giardiasis. MetRS inhibitors, as validated by Compound-1717, have promising anti-giardiasis properties that merit further study as alternative therapeutics.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model

2018 ◽  
Vol 53 (5) ◽  
pp. 567-574 ◽  
Author(s):  
Ricardo A. Mosquera ◽  
Wilfredo De Jesus-Rojas ◽  
James M. Stark ◽  
Aravind Yadav ◽  
Cindy K. Jon ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Infection Model ◽  
Mouse Infection Model ◽  
Mouse Infection

scholarly journals YersiniaOuter Protein P Inhibits CD8 T Cell Priming in the Mouse Infection Model

2005 ◽  
Vol 174 (7) ◽  
pp. 4244-4251 ◽  
Author(s):  
Konrad Trülzsch ◽  
Gernot Geginat ◽  
Thorsten Sporleder ◽  
Klaus Ruckdeschel ◽  
Reinhardt Hoffmann ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Infection Model ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
T Cell Priming

Drug delivery using novel nanoplexes against a Salmonella mouse infection model

2009 ◽  
Vol 12 (3) ◽  
pp. 905-914 ◽  
Author(s):  
A. Ranjan ◽  
N. Pothayee ◽  
M. Seleem ◽  
N. Jain ◽  
N. Sriranganathan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Infection Model ◽  
Mouse Infection Model ◽  
Mouse Infection

Comparative chemotherapeutic acitivity of new fluorinated 4-quinolones and standard agents against a variety of bacteria in a mouse infection model

1989 ◽  
Vol 23 (5) ◽  
pp. 729-736 ◽  
Author(s):  
Josephine C. Sesnie ◽  
Peter W. Fritsch ◽  
Timothy J. Griffin ◽  
Carl L. Heifetz ◽  
Evangeline T. Leopold ◽  
...  
Keyword(s):  
Infection Model ◽  
Mouse Infection Model ◽  
Mouse Infection

scholarly journals Insight Into the Virulence Related Secretion Systems, Fimbriae, and Toxins in O2:K1 Escherichia coli Isolated From Bovine Mastitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Sun ◽  
Xing Gao ◽  
Kejie Zhao ◽  
Jiale Ma ◽  
Huochun Yao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bovine Mastitis ◽  
Systemic Infection ◽  
Infection Model ◽  
Secretion Systems ◽  
E Coli ◽  
Bacterial Pathogenicity ◽  
Mouse Infection Model ◽  
Type Iv ◽  
Mouse Infection

Mastitis remains a major infection of dairy cows and an important issue for the dairy farmers, and Escherichia coli (E. coli) bovine mastitis is a disease of significant economic importance in the dairy industry. Our study identified six isolates belong to phylogroup B2 from 69 bovine mastitis E. coli strains. Except for one serotype O1 strain, all group B2 isolates were identified into serotype O2 and showed significantly higher mortality in the mouse infection than other phylogroups' strains. Genomic analyses and further tests were performed to examine the role of secretion systems, fimbriae, and toxins during the systemic infection of O2:K1 strain BCE049. Two integral T6SS loci and three predicted effectors clusters were found to assemble the functional T6SS complex and deliver diverse toxic effectors to modulate bacterial virulence in the mouse infection model. A total of four T4SS loci were harbored in the BCE049 genome, three of them are encoded in different plasmids, respectively, whereas the last one locates within the bacterial chromosome at FQU84_16715 to FQU84_16760, and was significantly involved in the bacterial pathogenicity. Numerous predicted pilus biosynthesis gene loci were found in the BCE049 genome, whereas most of them lost long fragments encoding key genes for the pili assembly. Unexpectedly, a type IV pilus gene locus locating at FQU84_01405 to FQU84_01335 in the plasmid 2, was found to be required for the full virulence of mastitis strain BCE049. It should be noted that a genetic neighborhood inserted with diverse genes is encoded by the plasmid 1, which harbors three prominent toxins including β-hemolysin, cytotoxic necrotizing factor 2 and cytolethal distending toxin type III. Consequent studies verified that these toxins significantly contributed to the bacterial pathogenicity. These findings provide a molecular blueprint for understanding the underlying mechanisms employed by the bovine mastitis E. coli to colonize in host and cause systemic infection.

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