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In this study, we determined the complete coding sequence of a putative new member of the family Flaviviridae, named “Cyclopterus lumpus virus” (CLuV), which is associated with a serious disease in lumpfish (Cyclopterus lumpus). The virus was present in all tissues tested, but pathology was primarily observed in the liver and kidneys. CLuV shows low but distinct similarity to the unassigned Tamana bat virus (TABV). Unlike other known members of the family Flaviviridae, translation of the entire CLuV polyprotein is dependent on a − 1 ribosomal frameshift in the NS2A region.

Deacetylation of α-tubulin at lysine 40 is catalyzed by two enzymes, the NAD-dependent deacetylase SIRT2 and the NAD-independent deacetylase HDAC6, in apparently redundant reactions. In the present study, we tested whether these two enzymes might have distinguishable preferences for the deacetylation of different microtubule structures. Using various agents, we induced tubulin hyperacetylation and analyzed the ensuing formation of distinct microtubule structures. HDAC6 inhibition led to general hyperacetylation of the microtubule network throughout the cell, whereas hyperacetylation induced by SIRT2 inactivation was limited to perinuclear microtubules. Hyperacetylation of these perinuclear microtubules was undiminished following HDAC6 overexpression, whereas reactivation of SIRT2 restored the basal acetylation level and a normal microtubule network. By contrast, SIRT2 and HDAC6 acted similarly on the morphologically different, hyperacetylated microtubule structures induced by taxol, MAP2c overexpression or hyperosmotic stress. These results indicate overlapping and distinct functions of HDAC6 and SIRT2. We propose that the differential activity of the two deacetylases, which target the same acetylated lysine residue, might be related to the recognition of specific structural contexts.

Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.