Comparative analysis of 22 Epstein-Barr virus genomes from diseased and healthy individuals.

Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variations might influence EBV-associated diseases and their geographical patterns. In the present study, 22 EBV whole-genome sequences from diseased and healthy individuals were analysed to explore EBV sequence variations at the whole-genome level. We found that the 22 EBV genomes were generally highly similar to each other at the genome level. However, varying degrees of genetic diversity were detected across the entire genome, especially in the latent genes. In contrast, the sequences of promoters and non-coding RNAs were strictly conserved. These findings suggested that both latent genes and non-coding RNAs play important roles in the EBV life cycle. When we investigated changes in known T-cell epitopes in some latent and lytic proteins, we observed that some T-cell epitopes were changed, while others were conserved. These findings indicate that the effect of EBV variations in protein sequences that seem to have been selected by the host immune system should be considered when conducting EBV-targeted immunotherapy. Taken together, our results provide a global view of EBV genome sequence variation, which not only is important for designing vaccines and immunotherapy for EBV but also adds to the understanding of EBV biology and the relationships between viral sequence variation and EBV-associated diseases.

Effects of Helicobacter pylori infection on MUC5AC protein expression in gastric cancer.

AIM: To investigate the effects of the expression of the MUC5AC protein in gastric cancer depending on the Helicobacter pylori (Hp) infection status. MATERIALS & METHODS: The MUC5AC protein and mRNA were detected using western blot and real-time PCR protocols in gastric cancer tissue and stratified for Hp infection. Gastric mucus membranes near the cancer site serve as the control group. RESULTS: The expression of MUC5AC protein and mRNA is significantly decreased in gastric cancer tissue (p < 0.05). The decrease was more significant in the Hp-infected group than in the Hp-uninfected group (p < 0.05). CONCLUSION: The infection of Hp is correlated with a decrease in MUC5AC protein amount in gastric cancer tissue. The current result suggests that there may be a potential necessary link between Hp, MUC5AC and gastric cancer.

Clinical relevance of serum α-l-fucosidase activity in the SARS-CoV-2 infection.

BACKGROUND AND AIMS: The reduced fucosylation in the spike glycoprotein of SARS-CoV-2 and the IgG antibody has been observed in COVID-19. However, the clinical relevance of α-l-fucosidase, the enzyme for defucosylation has not been discovered. MATERIALS AND METHODS: 585 COVID-19 patients were included to analyze the correlations of α-l-fucosidase activity with the nucleic acid test, IgM/IgG, comorbidities, and disease progression. RESULTS: Among the COVID-19 patients, 5.75% were double-negative for nucleic acid and antibodies. All of them had increased α-l-fucosidase, while only one had abnormal serum amyloid A (SAA) and C-reactive protein (CRP). The abnormal rate of α-l-fucosidase was 81.82% before the presence of IgM, 100% in the presence of IgM, and 66.2% in the presence of IgG. 73.42% of patients with glucometabolic disorders had increased α-l-fucosidase activity and had the highest mortality of 6.33%. The increased α-l-fucosidase was observed in 55.8% of non-severe cases and 72.9% of severe cases, with an odds ratio of 2.118. The α-l-fucosidase mRNA was irrelevant to its serum activity. CONCLUSION: The change in α-l-fucosidase activity in COVID-19 preceded the IgM and SAA and showed a preferable relation with glucometabolic disorders, which may be conducive to virus invasion or invoke an immune response against SARS-CoV-2.

Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma.

About 10 % of gastric carcinoma worldwide is associated with EBV, which is defined as EBV-associated gastric carcinoma (EBVaGC). To date, EBV sequence data from EBVaGC in Guangdong, China, an endemic area of nasopharyngeal carcinoma (NPC), are not available. In the present study, two EBV genomes from EBVaGC specimens from Guangdong (designated as GDGC1 and GDGC2) were determined by next-generation sequencing, de novo assembly and joining of contigs by Sanger sequencing. In addition, we sequenced EBV from two Korean EBVaGC cell lines, YCCEL1 and SNU-719. Genomic diversity, including single nucleotide polymorphisms (SNPs) and insertions and deletions (indels), phylogenetic analysis and rates of protein evolution, was performed using bioinformatics software. The four gastric carcinoma-derived EBV (GC-EBV) were all type I. Compared with the reference EBV genome, a total of 1815 SNPs (146 indels), 1519 SNPs (106 indels), 1812 SNPs (126 indels) and 1484 SNPs (106 indels) were found in GDGC1, GDGC2, YCCEL1 and SNU-719, respectively. These variations were distributed across the entire genome, especially in latent genes. In contrast, the sequences of promoters and non-coding RNAs were strictly conserved. Phylogenetic analyses suggested the presence of at least two parental lineages of EBV among the GC-EBV genomes. Rates of protein evolution analyses showed that lytic genes were under purifying selection; in contrast, latency genes were under positive selection. In conclusion, this study determined the EBV genomes in EBVaGC from Guangdong and performed a detailed genome-wide analysis of GC-EBV, which would be helpful for further understanding of the relationship between EBV genomic variation and EBVaGC carcinogenesis.

The changes in MUC5AC expression in gastric cancer before and after Helicobacter pylori eradication.

PURPOSE: To investigate MUC5AC expression in gastric cancer before and after Hp eradication. METHODS: The MUC5AC protein and mRNA were detected in gastric cancer tissue by western blot and real time PCR protocols before and after Hp eradication (Hp positive group). Gastric cancer tissue without Hp infection served as the control group (Hp negative group). RESULTS: The MUC5AC protein and mRNA expression was more significantly increased in gastric cancer after Hp eradication as compared to that before Hp eradication, but it was significantly lower than of the control group. The relative amount of MUC5AC in the well-differentiated cancer was higher than that of the moderately or poorly-differentiated cancer, in either Hp positive or control groups. The relative amount of MUC5AC in cancer tissues with more than five metastatic lymph nodes was significantly lower than that of the cancer tissues with five or less metastatic lymph nodes, and was significantly lower in the Hp positive group as compared to that of the control group. CONCLUSIONS: The reduction of the MUC5AC might be related to gastric carcinogenesis caused by Hp and the progression of gastric cancer.