Population dynamics at neuraminidase position 151 of influenza A (H1N1)pdm09 virus in clinical specimens.

Influenza A virus mutates rapidly, allowing it to escape natural and vaccine-induced immunity. Neuraminidase (NA) is a surface protein capable of cleaving the glycosidic linkages of neuraminic acids to release newly formed virions from infected cells. Genetic variants within a viral population can influence the emergence of pandemic viruses as well as drug susceptibility and vaccine effectiveness. In the present study, 55 clinical specimens from patients infected with the 2009 pandemic influenza A/H1N1 virus, abbreviated as A(H1N1)pdm09, during the 2015-2016 outbreak season in Taiwan were collected. Whole genomes were obtained through next-generation sequencing. Based on the published sequences from A(H1N1)pdm09 strains worldwide, a mixed population of two distinct variants at NA position 151 was revealed. We initially reasoned that such a mixed population may have emerged during cell culture. However, additional investigations confirmed that these mixed variants were detectable in the specimens of patients. To further investigate the role of the two NA-151 variants in a dynamic population, a reverse genetics system was employed to generate recombinant A(H1N1)pdm09 viruses. It was observed that the mixture of the two distinct variants was characterized by a higher replication rate compared to the recombinant viruses harbouring a single variant. Moreover, an NA inhibition assay revealed that a high frequency of the minor NA-151 variant in A(H1N1)pdm09 was associated with a reduced susceptibility to NA inhibitors. We conclude that two distinct NA-151 variants can be identified in patient specimens and that such variants may increase viral replication and NA activity.

Race with virus evolution: The development and application of mRNA vaccines against SARS-CoV-2.

Since the COVID-19 pandemic was declared, vaccines against SARS-CoV-2 have been urgently developed around the world. On the basis of the mRNA vaccine technology developed previously, COVID-19 mRNA vaccines were promptly tested in animals, advanced to clinical trials, and then authorized for emergency use in humans. The administration of COVID-19 mRNA vaccines has successfully reduced the hospitalization and mortality caused by the viral infection, although the virus continuously evolves with its transmission. Therefore, the development of mRNA vaccine technology, including RNA modification and delivery systems, is well recognized for its contribution to moderating the harms caused by the COVID-19 pandemic. The scientists who developed these technologies, Katalin Karikó, Drew Weissman, and Pieter Cullis, were awarded the 2022 Tang Prize in Biopharmaceutical Science. In this review, we summarize the principles, safety and efficacy of as well as the immune response to COVID-19 mRNA vaccines. Since mRNA vaccine approaches could be practical for the prevention of infectious diseases, we also briefly describe mRNA vaccines against other human viral pathogens in clinical trials.

Molecular Virology of SARS-CoV-2 and Related Coronaviruses.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global COVID-19 pandemic continues to threaten the lives of hundreds of millions of people, with a severe negative impact on the global economy. Although several COVID-19 vaccines are currently being administered, none of them is 100% effective. Moreover, SARS-CoV-2 variants remain an important worldwide public health issue. Hence, the accelerated development of efficacious antiviral agents is urgently needed. Coronavirus depends on various host cell factors for replication. An ongoing research objective is the identification of host factors that could be exploited as targets for drugs and compounds effective against SARS-CoV-2. In the present review, we discuss the molecular mechanisms of SARS-CoV-2 and related coronaviruses, focusing on the host factors or pathways involved in SARS-CoV-2 replication that have been identified by genome-wide CRISPR screening.

Effects on blood glucose, insulin, lipid and proatherosclerotic parameters in stable type 2 diabetic subjects during an oral fat challenge.

BACKGROUND: Restriction of fat intake has been effective in improving insulin sensitivity in obese and type 2 diabetic subjects, but what effects the recommended diet (less than 30% of total calories from fat) have not been elucidated in subjects with type 2 diabetes. The purpose of this study was to test the effects of oral fat challenge, composing 30% calories of a meal, on blood glucose, insulin, lipid, leptin, plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-alpha (TNF-alpha). DESIGN AND METHODS: Blood glucose, insulin, lipid, leptin, TNF-alpha and PAI-1 were compared in 14 type 2 diabetic patients and 10 normal subjects after an oral fat challenge upto 2 hours (fasting, 15 min, 30 min, 45 min, 60 min, 90 min and 120 min). RESULTS: Postprandial glucose, total cholesterol, leptin, PAI-1 levels did not differ significantly from levels at fasting. Serum triglyceride increased significantly from baseline only in diabetic patients (P = 0.042). Serum insulin increased postprandially in both groups (P = 0.028 in diabetic group and P = 0.055 in normal group), with displaying a prolonged insulin response in diabetic subjects. TNF-alpha decreased postprandially in both groups without significant difference, although diabetic patients have higher baseline levels (P = 0.024 compared to normal subjects). CONCLUSIONS: Oral fat load does not have an acute effect on blood glucose, total cholesterol, leptin and PAI-1 levels in both type 2 diabetic and normal subjects. TNF-alpha value showed decreased trend in both diabetic and normal subjects. The tendency of a delayed postprandial insulin response and elevated serum triglyceride level in diabetic subjects might be related to insulin resistance at the level of adipose tissue. Additional research is needed to assess the impact of the use of fat contents on the macronutrient composition of the diet, and potentially healthy and nutritional benefits for patients with diabetes.

Acute confusional state in type 2 diabetic patient: non-convulsive status epilepticus.

The etiology of acute confusional state in elderly patients with type 2 diabetes mellitus is broad, including hypoglycemia or hyperglycemia, electrolyte imbalance as hyponatremia or hypercalcemia, cerebrovascular disease and drug intoxication among others. Herein, we present an 80-year-old female type 2 diabetic patient in an acute confusional state due to non-convulsive status epilepticus (NCSE). Timely electroencephalogram at an emergency department when available is the only tool for the diagnosis of NCSE when clinically suspected. All clinicians must consider the possibility of NCSE in the differential diagnosis of acute confusional patients when diagnosis is uncertain.