Adrian R. Wilkie's research while affiliated with Harvard Medical School and other places

... In addition, its binding to myosin Va was identified. Interestingly, further data led to the statement that pUL53 might not be important for capsid transition towards the nuclear periphery [37]. A very prominent host factor of the multicomponent NEC has been identified with the multi-ligand binding protein p32/gC1qR. ...

... NHPs) and in three recent clinical trials following treatment with ONDs, in particular PS-ASO (volanesorsen, inotersen, and drisapersen) [84]. Two phenotypes of platelet count decrease have been distinguished: phenotype 1 characterized by a moderate but not clinically severe drop in platelet count and the rarer phenotype 2 of severe thrombocytopenia [85]. ...

... 4 In our recent work, we have focused on cell surface area, perimeter, circularity (FormFactor), pseudopodia (endpoint) number, and total pseudopodia length. 1 Examples of the processing steps from which these outputs are measured are seen in Figure 2. Cell morphology characteristics have been shown to change under various conditions, such as chronic stress. 1 Protocols similar to this have also been used in other biological contexts and cell types, demonstrating the broad applicability of quantifying cell morphology. 8,9 Cell morphology phenotypes can be indicative of organism characteristics; for example, differences in cell morphology have been associated with donor age more closely than other established biomolecular measurements such as DNA damage response or adenosine triphosphate content. 10 ...

... Recently, Sharda et al. [40] reported that the exocyst complex, in addition to supporting the trafficking of endolysosomal components to maturing WPB which is mediated by interactions with the biogenesis of lysosome-related organelle-2 (BLOC-2), can act at the plasma membrane as a clamp impeding WPB exocytosis. As this exocyst action could benefit from a tip-end orientation of WPB [40], we also analyzed a potential involvement of exocyst in Slp2-a tip-end enrichment. ...

... Unbiased bulk and single-cell transcriptomics paired with functional assays (fungal killing) of cells from patients infected with CMV demonstrated that human CMV-infected monocytes do not effectively phagocytose opportunistic fungal pathogens, and that this functional impairment occurs in the context of decreased expression of fungal PRRs 138 . Moreover, CMV-infected monocytes upregulate the expression of phagocytic receptors, pro-inflammatory chemokines, activate the inflammasome and induce the expression of innate immune transcripts associated with allograft rejection 138 . Notably, latent infection with CMV prevents the induction of prolonged allograft survival following transplantation and therefore represents a major barrier in kidney transplantation 139 . ...

... From platelet releasate [16] and CLSM co-localization studies [12] it has been suggested that selective release of proteins is due to different sets of proteins in the individual alphagranules, which then can be selectively released depending on stimulus. Differential packaging of proteins into alpha-granules has been reported to take place already upon platelet formation in the megakaryocytes [19]. However, higher resolution electron microscopy (EM) [20,21] and fluorescence super-resolution microscopy (SRM) [22,23] studies rather indicate that proteins are stored in clusters within individual alpha-granules, down to 50 nm in diameter, and with highly segregated protein cargo. ...

... What does FAM111A target in this antiviral mechanism? During SV40 infections, FAM111A localizes to viral replication centers (Tarnita et al., 2019). Depletion of FAM111A in infected cells results in higher viral replication center numbers (Tarnita et al., 2019), suggesting that FAM111A might proteolyze a key factor necessary for the viral replication process. ...

... The authors of this paper also hypothesized that Myo5b might play a role in the translocation of pre-ribosomal particles to the cytoplasm (Lindsay & McCaffrey, 2009), but the precise functions of Myo5a and b in the nucleus have not been elucidated. In terms of virus infections, colocalization in the nucleus was found between myosin-V motors and the nuclear replicating viruses Ad5 (Fuchsova et al., 2015), PRV (Feierbach, Piccinotti, Bisher, Denk, & Enquist, 2006), and human cytomegalovirus (HCMV) (Wilkie et al., 2018). Interestingly, for HCMV, RNAi experiments showed by electron microscopy that Myo5a silencing reduced the number of capsids in the cytoplasm but not in the nucleus, suggesting a role for Myo5a in nuclear egress (Wilkie et al., 2018). ...

... Thus, herpesviruses have emerged the specific mechanism of nuclear egress in order to bypass this barrier in a fine-regulated manner. Notably, the nuclear egress is a crucial step during the late phase of replication and is conserved among α-, β-, and γ-herpesviruses (Arii, 2021;Bigalke and Heldwein, 2017;Draganova et al., 2021;Hellberg et al., 2016;Lee and Chen, 2021;Lye et al., 2017;Marschall et al., 2017;Mettenleiter et al., 2013;Roller and Baines, 2017). This mechanism is mainly initiated by two viral proteins forming the core nuclear egress complex (NEC), which recruits cellular and viral proteins contained in a multicomponent NEC . ...

... Initially, nuclear actin was considered to be an artifact from cytoplasmic actin contamination (Zahler 2020). Thanks to the development of microscopy and actindetecting constructs fused with nuclear localization signal (NLS), convincing evidence of nuclear actin have been introduced (Baarlink et al. 2013;Lamm et al. 2020;Serebryannyy et al. 2016;Wilkie et al. 2016). For example, the endogenous nuclear F-actin and G-actin are detectable by using the actin-chromobody-GFP-NLS in the normal colon epithelial cells and mucinous colorectal cancer cells (Fig. 23.1e). ...