More than a half of plasma proteins are N-glycosylated. Most of them are synthesized, glycosylated, and secreted to the bloodstream by liver and lymphoid tissues. While associations with N-glycosylation are implicated in the rising number of liver, cardiometabolic, and immune diseases, little is known about the genetic regulation of this process. Here, we performed the largest genome-wide association study of N-glycosylation of the blood plasma proteome in 10,000 individuals. We doubled the number of genetic loci known to be associated with blood N-glycosylation by identifying 16 novel loci and prioritizing 13 novel genes contributing to N-glycosylation. Among these were the GCKR, TRIB1, HP, SERPINA1 and CFH genes. These genes are predominantly expressed in the liver and show a previously unknown genetic link between plasma protein N-glycosylation, metabolic and liver diseases, and inflammatory response. By integrating glycomics, proteomics, transcriptomics, and genomics, we provide a resource that facilitates deeper exploration of disease pathogenesis and supports the discovery of glycan-based biomarkers.
1 March 2024 in Molecular Genetics, Microbiology and Virology
Human respiratory syncytial virus (RSV) is an RNA virus of the family Pneumoviridae and is a common causative agent of acute respiratory infections. Infect
Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on RSV epidemiology and genotypic distribution across the FSU. Published studies from eLIBRARY and PubMed databases queried for RSV prevalence data, together with public health surveillance datasets, were used to summarize RSV prevalence research across eight FSU countries. Random-effects meta-analysis across age strata showed high prevalence in children before 6 (21%) and a progressive decline with age, which is in agreement with global data. Prevalence estimates showed a high degree of variability partially explained by study scope and clinical presentation. We observed COVID-19-related seasonal disruptions of RSV seasonality, followed by gradual post-pandemic stabilization. Genotypic data reflects global trends with two cosmopolitan clades, A.D and B.D, and their descendants, dominating in the region. The review is limited by uneven geographical and temporal coverage, and scarce data on adults. The review provides the first integrated summary of RSV epidemiology across the FSU and underscores the need for expanded regional surveillance and genomic reporting.
Cholangiocarcinoma (CCA), the second most common liver cancer, remains highly resistant to chemotherapy and radiotherapy, leaving patients with unresectable tumors in urgent need of innovative therapeutic approaches. Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA. Intratumoral administration of Ad6-d24-GM significantly suppressed tumor growth and prolonged survival without evidence of toxicity, as indicated by stable body weights and normal liver enzyme levels. Both Ad6-d24-GM and wild-type Ad6 induced robust infiltration of CD4+ and CD8+ T cells, as well as CD68+ macrophages within tumors, demonstrating activation of antitumor immunity. Notably, the Ad6-d24-GM group exhibited a statistically significant increase in CD68+ cells compared to wild-type Ad6, highlighting the immunomodulatory effect of GM-CSF transgene. These results demonstrate the oncolytic and immunostimulatory potential of Ad6-based vectors for CCA treatment and validate the Syrian hamster syngeneic CCA-OF model as a valuable platform for studying oncolytic adenovirus therapies.
28 March 2024 in Molecular Genetics Microbiology and Virology (Russian version)
Human respiratory syncytial virus (RSV) is an RNA virus of the Pneumoviridae family and is a common causative agent of acute respiratory infections. Infection with this virus is often severe and can result in fatalities and chronic complications, particularly in high-risk groups such as children under the age of 5 and elderly individuals over 65 years old. This review presents the latest data on the taxonomy, virion structure, and genome map of RSV, as well as its role in the etiology of acute respiratory diseases. We have analyzed over 100 publications on RSV genotyping in different parts of the world including Russia published between 2015 and 2023. The genetic composition of RSV isolates in Russia is similar to that in other regions of the world, predominantly represented by genotypes ON1 and BA9. The development of effective vaccines is crucial for successful disease control. The review summarizes global advances in the development of interventions against RSV, emphasizing promising treatments currently undergoing clinical trials and the ones that have recently been approved. Similar interventions (vaccines) are yet to be developed in Russia, but the similarities in genetic composition of RSV in Russia and worldwide offer hope for the rapid development of domestic vaccines against this infection.