Human adenoviruses (HAdVs) are uniquely important “model organisms” as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to “one-time” appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population.

Background Geminiviruses are circular, single-stranded viruses responsible for enormous crop loss worldwide. Rapid expansion of geminivirus diversity outweighs the continuous effort to control its spread. Geminiviruses channelize the host cell machinery in their favour by manipulating the gene expression, cell signalling, protein turnover, and metabolic reprogramming of plants. As a response to viral infection, plants have evolved to deploy various strategies to subvert the virus invasion and reinstate cellular homeostasis. Main body Numerous reports exploring various aspects of plant-geminivirus interaction portray the subtlety and flexibility of the host–pathogen dynamics. To leverage this pool of knowledge towards raising antiviral resistance in host plants, a comprehensive account of plant’s defence response against geminiviruses is required. This review discusses the current knowledge of plant’s antiviral responses exerted to geminivirus in the light of resistance mechanisms and the innate genetic factors contributing to the defence. We have revisited the defence pathways involving transcriptional and post-transcriptional gene silencing, ubiquitin-proteasomal degradation pathway, protein kinase signalling cascades, autophagy, and hypersensitive responses. In addition, geminivirus-induced phytohormonal fluctuations, the subsequent alterations in primary and secondary metabolites, and their impact on pathogenesis along with the recent advancements of CRISPR-Cas9 technique in generating the geminivirus resistance in plants have been discussed. Conclusions Considering the rapid development in the field of plant-virus interaction, this review provides a timely and comprehensive account of molecular nuances that define the course of geminivirus infection and can be exploited in generating virus-resistant plants to control global agricultural damage.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003–2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10 −4 mutations/site/year (95% highest posterior density 4.55 × 10 −4 to 5.38 × 10 −4 ) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10 −4 mutations/site/year, 95% highest posterior density 3.26 × 10 −4 to 3.94 × 10 −4 ). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.

Plant virus satellites are maintained by their associated helper viruses and satellites influence viral pathogenesis. Diseases caused by geminivirus-betasatellite complexes can become epidemics and therefore have become a threat to economically important crops across the world. Here, we identified a novel molecular function of the betasatellite-encoded pathogenicity determinant βC1. The tomato leaf curl Patna betasatellite (ToLCPaB)-encoded βC1 protein was found to exhibit novel ATPase activity in the presence of the divalent metal ion cofactor MgCl 2 . Moreover, ATPase activity was confirmed to be ubiquitously displayed by βC1 proteins encoded by diverse betasatellites. Mutational and sequence analysis revealed conserved lysine/arginine residues at positions 49/50 and 91 of βC1 proteins to be essential for their ATPase activity. Biochemical studies revealed the DNA-binding activity of the βC1 protein was interfered by the binding of ATP to the protein. Mutating arginine 91 of βC1 to alanine reduced its DNA-binding activity. The results of docking studies provided evidence for an overlap of the ATP-binding and DNA-binding regions of βC1 and for the importance of arginine 91 for both ATP-binding and DNA-binding activities. A mutant betasatellite with a specifically βC1-ATPase dominant negative mutation was found to induce symptoms on Nicotiana benthamiana plants similar to those induced by wild-type betasatellite infection. The ATPase function of βC1 was found to be negatively associated with geminivirus-betasatellite DNA accumulation, despite the positive influence of this ATPase function on the accumulation of replication-associated protein (Rep) and βC1 transcripts. Importance Most satellites influence the pathogenesis of their helper viruses. Here we characterized the novel molecular function of βC1, a non-structural, pathogenicity determinant protein encoded by a betasatellite. Here, we demonstrated the display of ATPase activity by this βC1 protein. Additionally, we confirmed the ubiquitous display of ATPase activity by βC1 proteins encoded by diverse betasatellites. The lysine/arginine residues conserved at positions 49 and 91 of βC1 were found to be crucial for its ATPase function. DNA-binding activity of βC1 was found to be reduced in the presence of ATP. Inhibition of ATPase activity of βC1 in the presence of an excess concentration of cold ATP, GTP, CTP or UTP suggested that the purified βC1 can also hydrolyze other cellular NTPs besides ATP in vitro. These results established the importance of the ATPase and DNA-binding activities of the βC1 protein in regulating the geminivirus-betasatellite DNA accumulation in the infected plant cell.

The transformation of a normal cell to cancer requires the derail of multiple pathways. Normal signaling in a cell is regulated at multiple stages by the presence of feedback loops, calibration of levels of proteins by their regulated turnover, and posttranscriptional regulation, to name a few. The tumor suppressor protein FBXO31 is a component of the SCF E3 ubiquitin ligase and is required to arrest cells at G1 following genotoxic stresses. Due to its growth-suppression activity, it is underexpressed in many cancers. However, the molecular mechanism underlying the translational regulation of FBXO31 remains unclear. Here we show that the oncogenic microRNAs miR-93 and miR-106a repress FBXO31, resulting in the upregulation of Slug, which is involved in epithelial-mesenchymal transition and cell invasion. FBXO31 targets and ubiquitylates Slug for proteasomal degradation. However, this mechanism is repressed in breast tumors where miR-93 and miR-106a are overexpressed. Our study further unravels an interesting mechanism whereby Slug drives the expression of miR-93 and miR-106a, thus establishing a positive feedback loop to maintain an invasive phenotype. Together, these results establish the presence of interplay between microRNAs and the ubiquitination machinery, which together regulate cancer cell invasion.