Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus.

BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.

Usefulness of FDG-PET/CT-Based Radiomics for the Characterization and Genetic Orientation of Pheochromocytomas Before Surgery.

PURPOSE: To assess the potential added value of FDG-PET/CT radiomics for the characterization of pheochromocytomas (PHEO) and their genetic orientation prior to surgery and genetic testing. METHODS: This retrospective monocentric study, included 49 patients (52 tumors) that underwent both FDG-PET/CT and MIBG scan before surgery. A germline mutation was secondarily identified in 13 patients in one of the genes related to Cluster 1 (n = 4) or Cluster 2 (n = 9). No mutation was identified in 32 patients and 4 did not have genetic testing. Correlation between several PET-based biomarkers, including SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and textural features, and biochemical and genetic features were analyzed. RESULTS: Sensitivity of FDG-PET/CT alone was 92%, and 98% when combined to MIBG. The SUVmax was significantly higher for mutated tumors classified in Cluster 1 than in Cluster 2 (p = 0.002) or for tumors with no identified mutations (p = 0.04). MTV and TLG of the tumors with the most intense uptake discriminated mutated Cluster 2 from sporadic tumors, but not from Cluster 1 tumors. Textural features combined with MTV led to better differentiation between sporadic and mutated tumors (p < 0.05). CONCLUSION: FDG-PET/CT is useful for preoperative characterization of PHEO, and when combined with radiomics biomarkers, provides evidences for a genetic predisposition.