Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis

Coronavirus porcine epidemic diarrhea virus (PEDV) is classified in the genu

Molecular epidemiology of hepatitis E virus infections in Shanghai, China

<p>Abstract</p> <p>Background</p> <p>Hepatitis E virus (HEV) causes acute or fulminant hepatitis in humans and is an important public health concern in many developing countries. China has a high incidence of HEV epidemics, with at least three genotypes (1, 3 and 4) and nine subtypes (1b, 1c, 3b, 4a, 4b, 4d, 4g, 4h and 4i) so far identified. Since genotype 3 and the newly identified subtype 4i have been exclusively limited geographically to Shanghai and its neighboring provinces, the epidemiology of HEV infections within the municipality, a major industrial and commercial center, deserves closer attention.</p> <p>Findings</p> <p>A total of 65 sequences, 60 located within the HEV SH-SW-zs1 genome [GenBank:<ext-link ext-link-id="EF570133" ext-link-type="gen">EF570133</ext-link>], together with five full-length swine and human HEV genomic sequences, all emanating from Shanghai, were retrieved from GenBank. Consistent with the primary role of genotype 4 in China overall, analysis of the sequences revealed this to have been the dominant genotype (58/65) in Shanghai. Six HEV subtypes (3b, 4a, 4b, 4d, 4h and 4i) were also represented. However, although subtype 4a is the dominant subtype throughout China, subtype 4i (29/65) was the most prevalent subtype among the Shanghai sequences, followed by subtypes 4d (10/65) and 4h (9/65). Subtypes 4h, 4i and 4d were found in both swine and humans, whereas 4b was found only in swine and subtype 4a only in humans.</p> <p>Conclusions</p> <p>Six different swine and human HEV subtypes have so far been documented in Shanghai. More molecular epidemiological investigations of HEV in swine, and particularly among the human population, should be undertaken.</p

Glass-Forming Ability and Thermal Properties of Al70Fe12.5V12.5X5(X = Zr, Nb, Ni) Amorphous Alloys via Minor Alloying Additions

The Al70Fe12.5V12.5Ni5, Al70Fe12.5V12.5Zr5 and Al70Fe12.5V12.5Nb5 alloys were prepared via mechanical alloying. The influence of Zr, Nb or Ni addition on the glass-forming ability of Al-Fe-V amorphous alloys have been investigated. The structure of Al70Fe12.5V12.5Ni5 was amorphous and Al70Fe12.5V12.5Zr5 was not completely amorphous by transmission electron microscopy, selected area electron diffraction and differential scanning calorimetry. Different criteria were used to evaluate the influence of the addition of alloy elements on the Glass-forming ability. The Al70Fe12.5V12.5Ni5 amorphous alloys exhibits higher glass-forming ability and activation energies of crystallization. Comparison of the effective atomic size ratio and mixture enthalpy on the glass-forming ability of these amorphous alloys demonstrates that the effective atomic size ratio value becomes more significant than the values of mixture enthalpy

Crystallization Behavior of Al₇₀Fe_12.5V_12.5Nb₅ Amorphous Alloy Formed by Mechanical Alloying

In this study, the formation and crystallization of the Al70Fe12.5V12.5Nb5 amorphous alloys has been investigated. The addition of Nb enhances the supercooled liquid region and glass forming ability of the Al-Fe-V amorphous alloys. The Al70Fe12.5V12.5Nb5 amorphous alloy exhibits two distinct crystallization steps and a large supercooled liquid region at more than 100 K. Kissinger and Ozawa analyses showed that the two activation energies for crystallization (Ex) were estimated to be 366.3 &#177; 23.9 and 380.5 &#177; 23.9 kJ/mol. Large supercooled liquid regions are expected to gain an application field of Al-based amorphous alloys

Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants

Abstract Background Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants. Results A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains. Conclusions One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.</p

Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells

The genomes of coronaviruses carry accessory genes known to be associated with viral virulence. The single accessory gene of porcine epidemic diarrhea virus (PEDV), ORF3, is dispensable for virus replication in vitro, while viral mutants carrying ORF3 truncations exhibit an attenuated phenotype of which the underlying mechanism is unknown. Here, we studied the effect of ORF3 deletion on the proliferation of PEDV in Vero cells. To this end, four recombinant porcine epidemic diarrhea viruses (PEDVs) were rescued using targeted RNA recombination, three carrying the full-length ORF3 gene from different PEDV strains, and one from which the ORF3 gene had been deleted entirely. Our results showed that PEDVs with intact or naturally truncated ORF3 replicated to significantly higher titers than PEDV without an ORF3. Further characterization revealed that the extent of apoptosis induced by PEDV infection was significantly lower with the viruses carrying an intact or C-terminally truncated ORF3 than with the virus lacking ORF3, indicating that the ORF3 protein as well as its truncated form interfered with the apoptosis process. Collectively, we conclude that PEDV ORF3 protein promotes virus proliferation by inhibiting cell apoptosis caused by virus infection. Our findings provide important insight into the role of ORF3 protein in the pathogenicity of PEDV

Antigenicity Alternations of Variant PEDV S Protein Disclosed by Linear B Cell Epitope Mapping

The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a significant question how much accumulation of antigenic shift could lead to the antigenic escape of the variant PEDV. To provide an answer in the study, B cell epitopes (BCEs) on the S protein of the PEDV vaccine strain CV777 (SCV777) and variant strain SD2014 (SSD2014) were mapped using biosynthetic peptides and rabbit anti-PEDV S serum. Seventy-nine and 68 linear BCEs were identified from SCV777 and SSD2014, respectively. While 66.2% of the BCEs of SSD2014 could be recognized by anti-SCV777 serum and 67.1% of SCV777 BCEs could be recognized by anti-SSD2014 serum, more than 40% of the BCEs identified using anti-SCV777 serum on SCV777 could not be recognized by anti-SSD2014 serum and vice versa. The completely shared BCEs took low percentages of 29.4% and 25.3% for SSD2014 and SCV777, respectively. These results indicate a low conservation of antigenicity of the S protein compared to a relatively high amino acid sequence similarity of 92.2% between the two strains. The study provided a BCE shift reference of PEDV antigenic escape and surveillance control

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus In Vitro and In Vivo

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC50 values of 2.53, 3.50, and 6.69 &mu;M, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment

Study on Regulation Mechanism of Tomato Root Growth in Greenhouse under Cycle Aerated Subsurface Drip Irrigation

Aerobic irrigation can effectively improve the oxygen environment in the root zone, and enhance crop quality and yield. However, how aerobic irrigation regulates root growth has not been elucidated. In this study, tomato plants were irrigated with three levels of oxygen (high, medium, and low) under underground drip irrigation. The morphology, activity, transcriptome, and hormone content of tomato roots under oxygen irrigation were analyzed. We found that the aeration irrigation significantly promoted root development. Notably, in the high-aeration irrigation treatment (HAI), the total root length, total surface area, total volume, and root activity were 12.41%, 43.2%, 79.1%, and 24.15% higher than in the non-aeration irrigation treatment (CK), respectively. The transcriptome of tomato roots under aeration irrigation was determined with a total of 272 differentially expressed genes (DEGs), including 131 up-regulated and 141 down-regulated genes. The Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed that the DEGs were enriched mainly in the metabolic pathways and plant hormone signal transduction. Among the plant hormone signal transduction, 50% of DEGs belonged to IAA signal-related genes and were upregulated. LC-MS analysis showed that the content of auxin hormones in the tomato roots subjected to aeration irrigation was significantly higher than that in CK. The content of Indole-3-acetic acid (IAA), Indole-3-carboxylic acid (ICA) and Indole-3-carboxaldehyde (ICAld) were 2.3, 2.14 and 1.45 times higher than those of the CK, but insignificant effects were exerted on the contents of cytokinins, salicylic acid, jasmonic acid, abscisic acid, and ethylene. Meanwhile, the key enzyme of auxin synthesis flavin monooxygenase (YUCCA) was significantly up-regulated. The aforementioned results show that aeration irrigation may promote the growth and development of roots by auxin regulation

SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex

Background: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. Methods: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions. Results: We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways. Conclusion: Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells. Electronic supplementary material The online version of this article (10.1186/s12943-018-0824-y) contains supplementary material, which is available to authorized users