Improved walking energy efficiency might persist in presence of simulated full weight regain after multidisciplinary weight loss in adolescents with obesity: the POWELL study.

AIM: Weight loss leads to a reduction of the energy cost of walking but the respective implications of the metabolic and mechanic changes remain unknown. The present study compares the post-weight loss energy cost of walking (Cw) with and without a total reload of the induced weight reduction in adolescents with obesity. METHODS: Energy cost of walking and substrate use were evaluated during a graded walking exercise (4×6-min at 0.75, 1, 1.25, 1.5 m.s-1) before (V1) and after a 12-week intervention in 21 adolescents with obesity (11 girls; 13.8 ± 1.4 y). After weight loss, the walking exercise was randomly repeated once without weight reload (V2) and once with a loading corresponding to the total induced weight loss during the program (V2L). Body composition was assessed before and after the intervention. RESULTS: Body weight and fat mass decreased in response to the 12-week intervention (p < 0.001), while FFM did not change. The absolute gross Cw (ml.m-1) was higher on V1 compared with V2 at every speed. The absolute net Cw (ml.m-1) was higher on V1 compared to V2L at 0.75 m.s-1 (p = 0.04) and 1 m.s-1 (p = 0.02) and higher on V2L compared with V2 at 1.5 m.s-1 (p = 0.03). Net Cw (ml.m-1.kg-1) on V1 being higher than V2 (p < 0.001), and V2L higher than V2 (p = 0.006). The absolute CHO oxidation (mg.min-1) did not show any condition effect (p = 0.12) while fat utilization was higher on V1 compared to V2 and V2L (p < 0.001). Relative to body weight CHO oxidation was lower on V1 compared to V2 (p = 0.04) and V2L (p = 0.004) while relative to body weight fat oxidation was higher on V1 than V2 (p = 0.002). CONCLUSION: Adolescents with obesity might not show an entire rise back to pre-weight loss values of their metabolic cost of walking when weight gain is simulated. These new findings suggest metabolic and physiological adaptations to weight loss of the energy metabolism that remain to be clarified.

Monoclonal antibodies to gp100 inhibit penetration of human herpesvirus 6 and polykaryocyte formation in susceptible cells.

We report the derivation and properties of a monoclonal antibody (MAb 2E4) which neutralizes human herpesvirus 6 (HHV-6). MAb 2E4 precipitated from lysates of infected cells a glycosylated polypeptide 100,000 in apparent molecular weight and minor components of 80,000, and 32,500. The predominant reactive protein after a pulse was the 100,000-molecular-weight peptide designated as gp100. The smaller polypeptides appeared in the precipitate predominantly after a chase. MAb 2E4 neutralized HHV-6 infectivity in the presence and in the absence of complement, and it inhibited the penetration of virus into the cells. Addition of MAb 2E4 as late as 6 h postinfection inhibited the formation of large polykaryocytes typical of HHV-6-infected cells.

Herpes simplex virus (HSV) glycoprotein H is partially processed in a cell line that expresses the glycoprotein and fully processed in cells infected with deletion or ts mutants in the known HSV glycoproteins.

Cell lines that constitutively express herpes simplex virus 1 (HSV-1) glycoprotein H (gH-1) failed to synthesize the mature form of gH and accumulated a precursor-like form of the glycoprotein, which was retained intracellularly, most likely in RER. Fine-structure analysis of the oligosaccharides present in recombinant gH revealed oligosaccharides processed by RER enzymes; sialylated complex-type and biantennary oligosaccharides, which are assembled in the trans-Golgi, were absent. A small fraction had the characteristics of oligosaccharides processed by the early mannosidases of the Golgi. These findings suggest that a defect in the transport out of RER to the Golgi may account for the intracellular retention of the immature form of gH in cells that express the glycoprotein constitutively. Upon superinfection of cells expressing gH-1 with HSV-2, recombinant gH-1 underwent maturation, indicating that a viral function is required to attain full processing of gH. The known HSV glycoproteins do not appear to carry out this function, since in cells infected with deletion mutants in gD, gG, gE, and gE-gI, with a spontaneous gC- mutant, or with a temperature-sensitive mutant in gB, maturation of gH occurred independently of the presence or of the maturation of the single glycoproteins tested. The present findings together with previous observations on HSV, human CMV, and the EBV homologue of gH suggest that inability of gH to undergo full processing in the absence of viral protein(s) is a property of gH.

Glycoprotein C-dependent attachment of herpes simplex virus to susceptible cells leading to productive infection.

Herpes simplex viruses encode several glycoproteins dispensable for infection and replication in cell culture. Evidence is presented that there exist at least two pathways for viral attachment to cells, i.e., one mediated by the dispensable glycoprotein C (gC) and one independent of that glycoprotein. Thus, whereas the polycations neomycin and polylysine inhibit attachment but not entry of already attached herpes simplex virus 1 (HSV-1) into baby hamster kidney (BHK) cell line, they have no effect on HSV-2 attachment to the same cells (N. Langeland, H. Holmsen, G.R. Lilehaug, and L. Haarr, 1987, J. Virol. 61, 3388-3393; N. Langeland, L.J. Moore, H. Holmsen, and L. Haarr, 1988, J. Gen. Virol. 69, 1137-1145). We report that (i) analyses of intertypic HSV-1 X HSV-2 recombinants indicated that the HSV-2 locus which confers ability to infect BHK cells in the presence of neomycin or polylysine comaps with the gene specifying gC but not with or near the genes specifying the other viral glycoproteins (gB, gD, gE, and gG, and gI), (ii) the smallest HSV-2 DNA fragment capable of transferring this function to HSV-1 was a 2880-bp Sa/l fragment encoding the entire gC (UL44 open reading frame) gene, 515 bp of coding sequences from the UL43 open reading frame and 393 bp of coding sequences from the UL45 open reading frame, but analyses of the recombinant virus DNA excluded UL43 and most of the UL45 sequences, and (iii) definitive evidence that HSV-2 gC confers upon HSV the capacity to infect BHK cells in the presence neomycin or polylysine emerged from studies showing that site-specific mutagenesis which inactivated the gene yielded a recombinant whose attachment to BHK cells was blocked by the polycations. We conclude that in BHK cells there exists in addition to the pathway blocked by neomycina and polylysine a pathway which is parallel and HSV-2 gC dependent.