Models of Herpes Simplex Virus Latency.

Our current understanding of HSV latency is based on a variety of clinical observations, and in vivo, ex vivo, and in vitro model systems, each with unique advantages and drawbacks. The criteria for authentically modeling HSV latency include the ability to easily manipulate host genetics and biological pathways, as well as mimicking the immune response and viral pathogenesis in human infections. Although realistically modeling HSV latency is necessary when choosing a model, the cost, time requirement, ethical constraints, and reagent availability are also equally important.

Herpes Simplex Virus 1 ICP34.5 Alters Mitochondrial Dynamics in Neurons.

Expression of viral genes and activation of innate antiviral responses during infection result in an increase in reactive oxygen species (ROS) and toxic by-products of energy metabolism which can lead to cell death. The mitochondrion and its associated proteins are crucial regulators of these responses and related pathways such as autophagy and apoptosis. Through a mass spectrometry approach, we have shown that the herpes simplex virus 1 (HSV-1) neurovirulence- and autophagy-modulating protein ICP34.

The US11 Gene of Herpes Simplex Virus 1 Promotes Neuroinvasion and Periocular Replication following Corneal Infection.

Herpes simplex virus 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation, US11 through preventing PKR activation and ICP34.5 through mediating dephosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α).

Neuronal Subtype Determines Herpes Simplex Virus 1 Latency-Associated-Transcript Promoter Activity during Latency.

Herpes simplex virus (HSV) latency in neurons remains poorly understood, and the heterogeneity of the sensory nervous system complicates mechanistic studies. In this study, we used primary culture of adult trigeminal ganglion (TG) mouse neurons in microfluidic devices and an model to examine the subtypes of sensory neurons involved in HSV latency. HSV-infected neurofilament heavy-positive (NefH) neurons were more likely to express latency-associated transcripts (LATs) than infected neurofilament heavy-negative (NefH) neurons.

Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is mediated by CUL7 E3 ligase.

Expression of the hominoid-specific TBC1D3 oncoprotein enhances growth factor receptor signaling and subsequently promotes cellular proliferation and survival. Here we report that TBC1D3 is degraded in response to growth factor signaling, suggesting that TBC1D3 expression is regulated by a growth factor-driven negative feedback loop. To gain a better understanding of how TBC1D3 is regulated, we studied the effects of growth factor receptor signaling on TBC1D3 post-translational processing and turnover.

Between a rock and a dry place: the water-stressed moss.

The earliest land plants faced a suite of abiotic stresses largely unknown to their aquatic algal ancestors. The descendants of these plants evolved two general mechanisms for survival in the relatively arid aerial environment. While the vascular plants or 'tracheophytes' developed tissue specializations to transport and retain water, the other main lineages of land plants, the bryophytes, retained a simple, nonvascular morphology.

The hominoid-specific oncogene TBC1D3 activates Ras and modulates epidermal growth factor receptor signaling and trafficking.

Hominoid- and human-specific genes may have evolved to modulate signaling pathways of a higher order of complexity. TBC1D3 is a hominoid-specific oncogene encoded by a cluster of eight paralogs on chromosome 17. Initial work indicates that TBC1D3 is widely expressed in human tissues ( Hodzic, D.

TBC1D3, a hominoid oncoprotein, is encoded by a cluster of paralogues located on chromosome 17q12.

TBC1D3 is a member of the TBC1 domain family of proteins that stimulates the intrinsic GTPase activity of RAB5A, an essential actor in early endosome trafficking. Oncogenic properties of TBC1D3 have been demonstrated previously both in vitro and in mouse models. Although the oncogenic mechanism of TBC1D3 has yet to be elucidated, the TBC1D3 locus (chromosome 17q12) is amplified in 15% of primary prostate tumors.

Mispolarization of desmosomal proteins and altered intercellular adhesion in autosomal dominant polycystic kidney disease.

Polycystin-1, the product of the major gene mutated in autosomal dominant polycystic kidney disease (ADPKD), has been shown to associate with multiple epithelial cell junctions. Our hypothesis is that polycystin-1 is an important protein for the initial establishment of cell-cell junctions and maturation of the cell and that polycystin-1 localization is dependent on the degree of cell polarization. Using laser-scanning confocal microscopy and two models of cell polarization, polycystin-1 and desmosomes were found to colocalize during the initial establishment of cell-cell contact when junctions were forming.

Molecular partitioning during host cell penetration by Toxoplasma gondii.

During invasion by Toxoplasma gondii, host cell transmembrane proteins are excluded from the forming parasitophorous vacuole membrane (PVM) by the tight apposition of host and parasite cellular membranes. Previous studies suggested that the basis for the selective partitioning of membrane constituents may be a preference for membrane microdomains, and this hypothesis was herein tested. The partitioning of a diverse group of molecular reporters for raft and nonraft membrane subdomains was monitored during parasite invasion by time-lapse video or confocal microscopy.

Host cells: mobilizable lipid resources for the intracellular parasite Toxoplasma gondii.

Successful replication of the intracellular parasite Toxoplasma gondii within its parasitophorous vacuole necessitates a substantial increase in membrane mass. The possible diversion and metabolism of host cell lipids and lipid precursors by Toxoplasma was therefore investigated using radioisotopic and fluorophore-conjugated compounds. Confocal microscopic analyses demonstrated that Toxoplasma is selective with regards to both the acquisition and compartmentalization of host cell lipids.