Capsid-mediated control of adeno-associated viral transcription determines host range.

Adeno-associated virus (AAV) is a member of the genus Dependoparvovirus, which infects a wide range of vertebrate species. Here, we observe that, unlike most primate AAV isolates, avian AAV is transcriptionally silenced in human cells. By swapping the VP1 N terminus from primate AAVs (e.g., AAV8) onto non-mammalian isolates (e.g., avian AAV), we identify a minimal component of the AAV capsid that controls viral transcription and unlocks robust transduction in both human cells and mouse tissue. This effect is accompanied by increased AAV genome chromatin accessibility and altered histone methylation. Proximity ligation analysis reveals that host factors are selectively recruited by the VP1 N terminus of AAV8 but not avian AAV. Notably, these include AAV essential factors implicated in the nuclear factor κB pathway, chromatin condensation, and histone methylation. We postulate that the AAV capsid has evolved mechanisms to recruit host factors to its genome, allowing transcriptional activation in a species-specific manner.

Intravital imaging of mouse embryos.

Embryonic development is a complex process that is unamenable to direct observation. In this study, we implanted a window to the mouse uterus to visualize the developing embryo from embryonic day 9.5 to birth. This removable intravital window allowed manipulation and high-resolution imaging. In live mouse embryos, we observed transient neurotransmission and early vascularization of neural crest cell (NCC)-derived perivascular cells in the brain, autophagy in the retina, viral gene delivery, and chemical diffusion through the placenta. We combined the imaging window with in utero electroporation to label and track cell division and movement within embryos and observed that clusters of mouse NCC-derived cells expanded in interspecies chimeras, whereas adjacent human donor NCC-derived cells shrank. This technique can be combined with various tissue manipulation and microscopy methods to study the processes of development at unprecedented spatiotemporal resolution.

Chocolate intake associated with failed labeling of (99m)Tc red blood cells.

UNLABELLED: Red blood cells (RBC) labeled in vivo with (99m)Tc-pertechnetate are used worldwide in nuclear medicine departments. METHODS: Here, we present a case of (99m)Tc-RBC labeling failure associated with chocolate intake in a 25-y-old woman, resulting in uninterpretable images. Because of this clinical observation, we performed in vitro RBC labeling on blood samples from volunteers after they consumed chocolate. RESULTS: Chocolate intake inhibited the labeling rate, compared with the control condition, and significantly increased the (99m)Tc free fraction (34.1% +/- 11.3% vs. 14.0% +/- 1.2%). CONCLUSION: We cannot explain how this interaction could occur, but cacao components are known to modulate red cell and plasma oxidoreductive status and to modify red cell membrane permeability and plasticity. Therefore, for patients who can be considered likely to consume chocolate, such as young patients, we recommend that they limit their consumption of chocolate for 12 h before RBC labeling.