Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional, nuclear protein involved in post-transcriptional regulation of a subset of viral genes during lytic replication. Three nuclear localization signals (NLSs), NLS1 (amino acids (aa 101-107), NLS2 (aa 121-130), and NLS3 (aa 143-152), were identified in the N terminus of the ORF57 protein, and each of the three represents a short stretch of basic amino acid residues. Disruption of all three NLSs prevented localization of ORF57 in the nucleus. Insertion of individual NLSs into a heterologous cytoplasmic protein converted it into a nuclear protein, confirming that each NLS functions independently and is sufficient to promote protein nuclear localization. Although it exhibits a function similar to that of Epstein-Barr virus EB2 in promoting KSHV ORF59 expression, KSHV ORF57 differs from the herpes simplex virus ICP27 protein, and its function could be disrupted by point mutations of single or two NLSs in random combination, despite the proper localization of the mutant protein in the nucleus. The dysfunctional ORF57 containing NLS mutations also had low affinity with ORF59 RNA and the RNA export factor REF. However, the REF binding of ORF57 in vivo appeared to have no effect on ORF57-mediated enhancement of ORF59 expression. Thus, the three NLSs identified in ORF57 provide at least two functions, nuclear localization of ORF57 and up-regulation of ORF59 expression.

A total of 245 patients undergoing MIPN were included in the study. The presence of APF was determined through keywords in operating notes, and radiographic data were obtained from preoperative cross-sectional imaging. Posterior fat thickness was measured between the renal capsule and the posterior abdominal wall at the level of the renal vein. Perinephric stranding was graded on a 0-3 severity scale. ResultsThe study included 123 men and 122 women, with a median age of 55 years, body mass index of 31.7, tumour size of 2.7 cm and nephrometry score of 6. The median posterior fat thickness was 1.79 cm and MAP score 2.63. In all, 26 patients (10.6%) had evidence of APF at the time of renal surgery. Factors predictive of APF included increasing age (P = 0.001), male gender (P = 0.045), perinephric stranding (P = 0.002), posterior fat thickness (P < 0.001) and MAP score (P < 0.001). APF was associated with adverse pathological and peri-operative outcomes including malignant renal histology (P = 0.04), longer operating time (P = 0.005) and greater estimated blood loss (EBL; P = 0.025). ConclusionsSpecific clinical and radiographic factors predict APF at MIPN. The presence of APF is associated with adverse perioperative outcomes including longer operating time and greater EBL. APF was also associated with renal malignancy on final pathology, but further studies are necessary to elucidate the precise underlying mechanism.

No abstract