In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Background Recent changes to the Food and Drug Administration boxed warning for metformin will increase use in individuals with historical contraindications or precautions. Prescribers must understand clinical outcomes of metformin use in these populations. Purpose To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate-to-severe chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment. Data Sources MEDLINE (via PubMed) from January 1994 to September 2016; Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection English-language studies that examined adults with type 2 diabetes and chronic kidney disease with eGFR <60 mL/min/1.73m2, congestive heart failure, or chronic liver disease with hepatic impairment; compared diabetes regimens that included metformin to regimens that did not; and reported all-cause mortality, major adverse cardiovascular events and other outcomes of interest. Data Extraction Two reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis Based on quantitative/qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, and chronic liver disease with hepatic impairment, and reduced heart failure readmission in patients with chronic kidney disease and congestive heart failure. Limitations We identified low strength of evidence and sparse data on multiple outcomes of interest. Available studies were observational and had varying follow-up durations. Conclusions Metformin use in patients with moderate chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support recent changes in metformin labeling. Registration PROSPERO CRD42016027708 Funding Source U.S. Department of Veterans Affairs

Lysine 2-hydroxyisobutyrylation (Khib) is an evolutionarily conserved and widespread histone mark like lysine acetylation (Kac). Here we report that EP300 functions as a lysine 2-hyroxyisobutyryltransferase to regulate glycolysis in response to nutritional cues. We discovered that EP300 differentially regulates Khib and Kac on distinct lysine sites, with only 6 of the 149 EP300-targeted Khib sites overlapping with the 693 EP300-targeted Kac sites. We demonstrate that diverse cellular proteins, particularly glycolytic enzymes, are targeted by EP300 for Khib, but not for Kac. Specifically, deletion of EP300 significantly reduces Khib levels on several EP300-dependent, Khib-specific sites on key glycolytic enzymes including ENO1, decreasing their catalytic activities. Consequently, EP300-deficient cells have impaired glycolysis and are hypersensitive to glucose-depletion-induced cell death. Our study reveals an EP300-catalyzed, Khib-specific molecular mechanism that regulates cellular glucose metabolism and further indicate that EP300 has an intrinsic ability to select short-chain acyl-CoA-dependent protein substrates.

Tick-borne viral diseases have attracted much attention in recent years because of their increasing incidence and threat to human health. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) and Heartland virus (HRTV) were recently identified as tick-borne phleboviruses (TBPVs) in Asia and the United States, respectively, and are associated with severe human diseases with similar clinical manifestations. In this study, we report the first identification and isolation of a novel TBPV named Guertu virus (GTV) from Dermacentor nuttalli ticks in Xinjiang Province, China, where TBPVs had not been previously discovered. Genome sequence and phylogenetic analyses showed that GTV is closely related to SFTSV and HRTV and was classified as a member of the genus Phlebovirus, family Phenuiviridae, order Bunyavirales. In vitro and in vivo investigations of the properties of GTV demonstrated that it was able to infect animal and human cell lines and can suppress type I interferon signaling, similar to SFTSV, that GTV nucleoprotein (NP) can rescue SFTSV replication by replacing SFTSV NP, and that GTV infection can cause pathological lesions in mice. Moreover, a serological survey identified antibodies against GTV from serum samples of individuals living in Guertu County, three of which contained neutralizing antibodies, suggesting that GTV can infect humans. Our findings suggested that this virus is a potential pathogen that poses a threat to animals and humans. Further studies and surveillance of GTV are recommended to be carried out in Xinjiang Province as well as in other locations.