The opportunistic human pathogenic fungus
is known to be infected with mycoviruses. In this study, we report a novel mycovirus
partitivirus 1 (AfPV1) that was originally isolated from the abnormal ...colonial morphology isolate LD-3-8 of
. AfPV1 has spherical virus-like particles about 40 nm in diameter, and three double-stranded RNA (dsRNA) segments (dsRNA1, 2, and 3 with lengths of 1.7, 1.4, and 1.1 kbp, respectively) were packaged in the virions. dsRNA1, dsRNA2, and dsRNA3 each contained a single open reading frame and potentially encoded 62, 42, and 32 kDa proteins, respectively. The dsRNA1 encoded protein shows similarity to the RNA-dependent RNA polymerase (RdRp) of partitiviruses, and the dsRNA2 product has no significant similarity to any other capsid protein (CP) in the GenBank databases, beside some homology with the hypothetical "capsid" protein of a few partitiviruses. The dsRNA3 encodes a protein with no similarity to any protein in the GenBank database. SDS-PAGE and polypeptide mass fingerprint-mass spectrum (PMF-MS) analyses indicated that the CP of the AfPV1 was encoded by dsRNA2. Phylogenetic analysis showed that the AfPV1 and relative viruses were found in an unclassified group inside the
family. AfPV1 seems to result in debilitation symptoms, but had no significant effects to murine pathogenicity. These findings provide new insights into the partitiviruses taxonomy and the interactions between viruses and
.
Abstract Helicobacter pylori ( H. pylori ), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, ap optosis, and the development of gastric cancer. Although lncRNA ...H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori . It was observed that cells infected with CagA + H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori . YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.
Abstract
Background
Helicobacter pylori
(
H. pylori
) can disrupt the tight junctions between gastric epithelial cells and penetrate the intercellular spaces acting on epithelial cells, normal ...fibroblasts (NFs), and cancer-associated fibroblasts (CAFs), but their interaction in gastric cancer tumorigenesis and progression remains unclear.
Methods
Primary CAFs and NFs were isolated from paired gastric cancer tissues and adjacent normal tissues and identified by immunofluorescence staining and western blot analysis for FSP-1, α-SMA, FAP, and vimentin expression. RNA-sequencing was used to compare the transcriptomes between CAFs and NFs. The expressions of FAP, lumican, and α-SMA, human cytokine array, and Transwell assay were used to assess the transformation of NFs to CAFs. CCK-8 assay, colony formation, flow cytometry, Transwell assay, and nude mouse xenograft model were used to determine the effects of Serpin E1 on cell proliferation and metastasis in vitro and in vivo. Finally, Serpin E1 and/or FAP expression was measured in
H. pylori
-infected gerbil gastric mucosa and human gastric cancer tissues.
Results
Gastric CAFs are inflammatory CAFs with α-SMA
low
FAP
high
lumican
high
. The interplay of
H. pylori
, fibroblasts, and cancer cells promotes the transition of NFs to CAFs by inducing cytokine release, especially Serpin E1. Long-term
H. pylori
infection and CAFs induce Serpin E1 expression in gerbil gastric tissues and human gastric cancer cells. Serpin E1 overexpression enhances the growth, migration, invasion of gastric cancer cells in vitro, and xenograft tumor growth in nude mice via inducing angiogenesis. Serpin E1 and FAP were highly expressed in cancer cells and CAFs of gastric cancer tissues, respectively, and a good correlation was observed between their expression. Higher Serpin E1 expression is negatively associated with the overall survival of patients with gastric cancer.
Conclusions
The interplay of
H. pylori
, fibroblasts, and cancer cells induced Serpin E1 expression to promote the activation of NFs to CAFs and gastric carcinogenesis. Targeting Serpin E1 will provide a promising therapeutic strategy for gastric cancer by disrupting the interaction between
H. pylori
, CAFs, and gastric cancer cells.
is an opportunistic pathogen that easily resists currently available antibiotics. Phages are considered alternative therapeutic agents to conventional antibiotics for the treatment of ...multidrug-resistant bacteria. We isolated an Acinetobacter virus Abgy202141 from underground sewage in a residential area of Guiyang City in China. Transmission electron microscopy (TEM) analysis showed that Acinetobacter virus Abgy202141 has an icosahedral head attached to a tail. This phage infects
strain GY-4, and was found to have a short latent period of 5 min and with a burst size of 189 particles per infected host cell. Additionally, Acinetobacter virus Abgy202141 remained stable at different concentrations of chloroform and varying pH levels and temperatures. Based on SDS-PAGE analysis, it contained 14 proteins with molecular weights ranging from 12 to 125 kDa. The double-strand (ds) DNA genome of Acinetobacter virus Abgy202141 consisted of 41,242 bp with a GC content of 39.4%. It contained 50 open reading frames (ORFs), of which 29 ORFs had identified functions, but no virulence-related genes, antibiotic-resistance genes, or tRNAs were found. Phylogenetic analysis indicated that Acinetobacter virus Abgy202141 was a new phage in the
genus. Acinetobacter virus Abgy202141 also showed the ability to prevent
infections in the
model.
The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of ...obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus_sp._CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila , Clostridium_sp._CAG:793 , Mycoplasma_sp._CAG:776 , Mycoplasma_sp._CAG:472 , Clostridium_sp._CAG:609 , Akkermansia_sp._KLE1605 , Clostridium_sp._CAG:508 , and Firmicutes_bacterium_CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1 , IGFBP6 , and IGFBP4 genes were highly correlated with Clostridium_sp._CAG:793 , and Akkermansia_glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity.
The bisegmented genome of a novel double-stranded (ds) RNA mycovirus, named “Aspergillus nidulans partitivirus 1” (AnPV1), isolated from the fungus
Aspergillus nidulans
strain HJ5-47, was sequenced ...and analyzed. AnPV1 contains two segments, AnPV1-1 and AnPV1-2. AnPV1-1 has 1837 bp with an open reading frame (ORF) that potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 572 amino acids (aa). AnPV1-2 has 1583 bp with an ORF encoding a putative capsid protein (CP) of 488 aa. Phylogenetic analyses indicated that AnPV1 and related viruses clustered in a group that could represent a new unclassified genus in the family
Partitiviridae
.
RNA interference (RNAi) is one of the important defense responses against viral infection, but its mechanism and impact remain unclear in mycovirus infections. In our study, reverse genetics and ...virus-derived small RNA sequencing were used to show the antiviral responses of RNAi components in
Aspergillus flavus
infected with Aspergillus flavus partitivirus 1 (AfPV1). qRT-PCR revealed that AfPV1 infection induced the expression of the RNAi components in
A. flavus
compared with noninfected
A. flavus
. Knock mutants of each RNAi component were generated, but the mutants did not exhibit any obvious phenotypic changes compared with the
A. flavus
parental strain. However, after AfPV1 inoculation, production of AfPV1 was significantly less than in the parental strain. Furthermore, sporulation was greater in each AfPV1-infected mutant compared with the AfPV1-infected parental
A. flavus
. We also investigated the sensitivity of virus-free and AfPV1-infected RNAi mutants and the parental strain to cell wall stress, osmotic stress, genotoxic stress, and oxidative stress. The mutants of DCLs and AGOs infected by AfPV1 displayed more changes than RDRP mutants in response to the first three stresses. Small RNA sequencing analysis suggested that AfPV1 infection reduced the number of unique reads of sRNA in
A. flavus
, although there were many vsiRNA derived from the AfPV1 genome. GO term and KEGG pathway analyses revealed that the functions of sRNA affected by AfPV1 infection were closely related to vacuole production. These results provide a better understanding of the functional role of RNAi in the impact of AfPV1 on the hypovirulence of
A. flavus
.
Aspergillus niger
is an important filamentous phytopathogenic fungus with a broad host range. A novel double-stranded (ds) RNA mycovirus, named
A
spergillus
n
iger
v
ictorivirus 1 (AnV1), isolated ...from
A. niger
strain baiyun3.23-4, was sequenced and analyzed. The AnV1 genome is 5317 nucleotides long with a GC content of 56%. AnV1 contains two open reading frames (ORF1 and 2), overlapping at a tetranucleotide sequence (AUGA). ORF1 encodes a putative capsid protein (CP) of 778 amino acids (aa), while ORF2 potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 826 aa. Phylogenetic analysis indicated that AnV1 is a new member of the genus
Victorivirus
in the family
Totiviridae
. As far as we know, this is the first report of the complete genome sequence of a victorivirus infecting
A. niger
.
The purpose of the present work was to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo acute myelogenous leukemia by sequencing the entire ...coding region. EZH2 mutations were identified in 13/714 (1.8%) of AML patients were found to be more common in males (P = 0.033). The presence of EZH2 mutations was significantly associated with lower blast percentage (21-30%) in bone marrow (P<0.0001) and -7/del(7q) (P = 0.025). There were no differences in the incidence of mutation in 13 genes, ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. No difference in complete remission, event-free survival, or overall survival was observed between patients with and without EZH2 mutation (P>0.05). Overall, these results showed EZH2 mutation in de novo acute myeloid leukemia as a recurrent genetic abnormality to be associated with lower blast percentage in BM and -7/del(7q).
PDF
