Polyomaviruses are small, non-enveloped viruses with a circular double-stranded DNA genome. Using a generic polyomavirus PCR targeting the VP1 major structural protein gene, a novel polyomavirus was initially identified in resected human liver tissue and provisionally named Human Polyomavirus 12 (HPyV12). Its 5033 bp genome is predicted to encode large and small T antigens and the 3 structural proteins VP1, VP2 and VP3. Phylogenetic analyses did not reveal a close relationship to any known human or animal polyomavirus. Investigation of organs, body fluids and excretions of diseased individuals and healthy subjects with both HPyV12-specific nested PCR and quantitative real-time PCR revealed additional virus-positive samples of resected liver, cecum and rectum tissues and a positive fecal sample. A capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV12. Seroprevalences of 23% and 17%, respectively, were determined in sera from healthy adults and adolescents and a pediatric group of children. These data indicate that the virus naturally infects humans and that primary infection may already occur in childhood.

Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess a unique "lariat knot" structural motif. Genome mining-targeted discovery of new natural products from microbes obtained from extreme environments has led to the identification of a gene cluster directing the biosynthesis of a new lasso peptide, designated as chaxapeptin 1, in the genome of Streptomyces leeuwenhoekii strain C58 isolated from the Atacama Desert. Subsequently, 1 was isolated and characterized using high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance methods. The lasso nature of 1 was confirmed by calculating its nuclear Overhauser effect restraint-based solution structure. Chaxapeptin 1 displayed a significant inhibitory activity in a cell invasion assay with human lung cancer cell line A549.

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Human polyomavirus 9 (HPyV9) was discovered recently in immunocompromised patients and shown to be genetically closely related to B-lymphotropic polyomavirus (LPyV). No serological data are available for HPyV9, but human antibodies against LPyV have been reported previously. To investigate the seroepidemiology of HPyV9 and the sero-cross-reactivity between HPyV9 and LPyV, a capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV9 and LPyV. VP1 of an avian polyomavirus was used as control. For HPyV9, a seroprevalence of 47 % was determined in healthy adults and adolescents (n5328) and 20 % in a group of children (n5101). In both groups, the seroreactivities for LPyV were less frequent and the ELISA titres of LPyV were lower. Of the HPyV9-reactive sera, 47 % reacted also with LPyV, and the titres for both PyVs correlated. Sera from African green monkeys, the natural hosts of LPyV, reacted also with both HPyV9 and LPyV, but here the HPyV9 titres were lower. This potential sero-cross-reactivity between HPyV9 and LPyV was confirmed by competition assays, and it was hypothesized that the reactivity of human sera against LPyV may generally be due to cross-reactivity between HPyV9 and LPyV. The HPyV9 seroprevalence of liver transplant recipients and patients with neurological dysfunctions did not differ from that of age-matched controls, but a significantly higher seroprevalence was determined in renal and haematopoietic stem-cell transplant recipients, indicating that certain immunocompromised patient groups may be at a higher risk for primary infection with or for reactivation of HPyV9. INTRODUCTIONHuman polyomavirus 9 (HPyV9) is the most recently identified of the nine human polyomaviruses (PyVs) reported to date, and was first detected in a renal transplant patient (Scuda et al., 2011). Later, the same virus was also found in human skin (Sauvage et al., 2011).PyVs are small, non-enveloped, circular dsDNA viruses. Primary infection with BK virus (BKV) and JC virus (JCV) occurs in childhood and is usually asymptomatic (Moens & Johannessen, 2008). Subsequently, these viruses establish a latent infection. Reactivation can occur in immunocompromised patients and cause serious disease, such as BKVassociated nephropathy or haemorrhagic cystitis (Gardner et al., 1971;Jiang et al., 2009), JCV-associated progressive multifocal leukoencephalopathy (Hou & Major, 2000;Jiang et al., 2009;Padgett et al., 1971) and trichodysplasia spinulosa caused by trichodysplasia spinulosa-associated PyV (Matthews et al., 2011;van der Meijden et al., 2010). PyVs have been shown to transform cells in vitro and to be tumorigenic in small laboratory rodents (Chen et al., 1989;Eddy et al., 1962;Gross, 1953;Stewart, 1953). BKV and JCV have been implicated aetiologically in a number of human cancers, but this issue is still controversial Maginnis & Atwood, 2009;zur Hausen, 2008). Merkel cell PyV (MCPyV) plays a causative role in Merkel cell carcinoma, a rare but aggressive skin cancer Feng et al., 2008).PyV serology has bee...

Background: p97 cooperates with cofactors to control various aspects of cellular homeostasis. Mutations at the interdomain interface cause a multisystem degenerative disorder. Results: We identified three binding epitopes on p97 for the N-terminal domain of cofactor UBXD1 (UBXD1-N), including disease-associated residues. Binding reduced p97 ATPase activity. Conclusion: UBXD1-N modulates interdomain communication and activity of p97. Significance: The polyvalent binding mode defines a new subset of p97 cofactors.