Structural basis for the interaction of human herpesvirus 6B tetrameric glycoprotein complex with the cellular receptor, human CD134

A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD  = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint

The combination of isomalto-oligosaccharides (IMO)-based dietary fiber and hypocaloric high-protein diet could improve the anthropometric profile and fasting plasma glucose of healthy adults: A repeated single-arm clinical trial

Background and aims: Meals with high protein and fiber could reduce weight and improve diabetes risk factors. Isomalto-oligosaccharide (IMO), a form of dietary fiber, could induce the afferent signal that causes appetite suppression. However, the direct effect of fiber supplementation in the form of IMO combined with a highprotein diet (HPF) on those parameters is still unknown. This study aims to investigate the effect of HPF on anthropometric parameters and blood glucose regulation of healthy subjects. Methods: Thirteen healthy subjects were given a hypocaloric high protein diet (HPD) mixed with their prepared meals for two weeks. Followed by the HPF diet for another two weeks. Their anthropometric parameters, such as body composition (total body weight, body fat percentage, and fat-free mass), BMI and waist circumference, and fasting plasma glucose, were measured. Results: Compared to pre-intervention, HPF could significantly (p ≤ 0.004) reduce the anthropometric parameters and fasting plasma glucose. Compared to HPD, HPF could significantly (p ≤ 0.005) reduce more total body weight, body fat percentage, and BMI. In addition, HPF could induce more satiety than HPD (higher VAS score). Conclusion: HPF could improve the subject’s anthropometric parameters which is obviously beneficial in preventing the risk of developing diabete

The combination of isomalto-oligosaccharides (IMO)-based dietary fiber and hypocaloric high-protein diet could improve the anthropometric profile and fasting plasma glucose of healthy adults: A repeated single-arm clinical trial

Background and aims: Meals with high protein and fiber could reduce weight and improve diabetes risk factors. Isomalto-oligosaccharide (IMO), a form of dietary fiber, could induce the afferent signal that causes appetite suppression. However, the direct effect of fiber supplementation in the form of IMO combined with a highprotein diet (HPF) on those parameters is still unknown. This study aims to investigate the effect of HPF on anthropometric parameters and blood glucose regulation of healthy subjects. Methods: Thirteen healthy subjects were given a hypocaloric high protein diet (HPD) mixed with their prepared meals for two weeks. Followed by the HPF diet for another two weeks. Their anthropometric parameters, such as body composition (total body weight, body fat percentage, and fat-free mass), BMI and waist circumference, and fasting plasma glucose, were measured. Results: Compared to pre-intervention, HPF could significantly (p ≤ 0.004) reduce the anthropometric parameters and fasting plasma glucose. Compared to HPD, HPF could significantly (p ≤ 0.005) reduce more total body weight, body fat percentage, and BMI. In addition, HPF could induce more satiety than HPD (higher VAS score). Conclusion: HPF could improve the subject’s anthropometric parameters which is obviously beneficial in preventing the risk of developing diabetes

The combination of isomalto-oligosaccharides (IMO)-based dietary fiber and hypocaloric high-protein diet could improve the anthropometric profile and fasting plasma glucose of healthy adults: A repeated single-arm clinical trial

Background and aims: Meals with high protein and fiber could reduce weight and improve diabetes risk factors. Isomalto-oligosaccharide (IMO), a form of dietary fiber, could induce the afferent signal that causes appetite suppression. However, the direct effect of fiber supplementation in the form of IMO combined with a high-protein diet (HPF) on those parameters is still unknown. This study aims to investigate the effect of HPF on anthropometric parameters and blood glucose regulation of healthy subjects. Methods: Thirteen healthy subjects were given a hypocaloric high protein diet (HPD) mixed with their prepared meals for two weeks. Followed by the HPF diet for another two weeks. Their anthropometric parameters, such as body composition (total body weight, body fat percentage, and fat-free mass), BMI and waist circumference, and fasting plasma glucose, were measured. Results: Compared to pre-intervention, HPF could significantly (p ≤ 0.004) reduce the anthropometric parameters and fasting plasma glucose. Compared to HPD, HPF could significantly (p ≤ 0.005) reduce more total body weight, body fat percentage, and BMI. In addition, HPF could induce more satiety than HPD (higher VAS score). Conclusion: HPF could improve the subject's anthropometric parameters which is obviously beneficial in preventing the risk of developing diabetes. © 2022 The Author(s

Tetrameric glycoprotein complex gH/gL/gQ1/gQ2 is a promising vaccine candidate for human herpesvirus 6B

Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine