Host-Dependent Differences in Replication Strategy of the Spindle-Shaped Virus Strain SSV9 (a.k.a., SSVK1): Infection Profiles in Hosts of the Family Sulfolobaceae.

The Spindle-shaped Virus (SSV) system has become a model for studying thermophilic virus biology, including archaeal host-virus interactions and biogeography. Several factors make the SSV system amenable to studying archaeal genetic mechanisms (e.g.

Stability and detection of nucleic acid from viruses and hosts in controlled mosquito blood feeds.

Monitoring the presence and spread of pathogens in the environment is of critical importance. Rapid detection of infectious disease outbreaks and prediction of their spread can facilitate early responses of health agencies and reduce the severity of outbreaks. Current sampling methods are sorely limited by available personnel and throughput.

A Three-Dimensional Cell Culture System To Model RNA Virus Infections at the Blood-Brain Barrier.

The blood-brain barrier (BBB) comprises the foremost protective barrier in the brain and is composed in part of a layer of microvascular endothelial cells that line the capillaries surrounding the brain. Here, we describe a human three-dimensional (3-D) cell-based model of the BBB microvascular endothelium that recapitulates properties of these cells , including physiologically relevant transcriptional profiles, the capacity to induce potent antimicrobial innate immune signaling, and the ability to resist infection by diverse RNA viruses, including members of the enterovirus (coxsackievirus B, echovirus 11, enterovirus 71, poliovirus) and flavivirus (dengue virus, Zika virus [ZIKV]) families. We show that disruption of apical tight junctions by proinflammatory cytokine tumor necrosis factor alpha (TNF-α) sensitizes 3-D-cultured BBB cells to ZIKV infection and that 3-D derived BBB cells can be used to model the transmigration of ZIKV-infected monocytes across the endothelial barrier to access underlying astrocytes.

Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner.

Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium.

A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity.

RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells.

Receptor interacting protein kinase-3 (RIP3) is an essential kinase for necroptotic cell death signaling and has been implicated in antiviral cell death signaling upon DNA virus infection. Here, we performed high-throughput RNAi screening and identified RIP3 as a positive regulator of coxsackievirus B3 (CVB) replication in intestinal epithelial cells (IECs). RIP3 regulates autophagy, a process utilized by CVB for viral replication factory assembly, and depletion of RIP3 inhibits autophagic flux and leads to the accumulation of autophagosomes and amphisomes.

Resistance to maribavir is associated with the exclusion of pUL27 from nucleoli during human cytomegalovirus infection.

Select mutations in the human cytomegalovirus (HCMV) gene UL27 confer low-grade resistance to the HCMV UL97 kinase inhibitor maribavir (MBV). It has been reported that the 608-amino acid UL27 gene product (pUL27) normally localizes to cell nuclei and nucleoli, whereas its truncation at codon 415, as found in a MBV-resistant mutant, results in cytoplasmic localization. We now show that in the context of full-length pUL27, diverse single amino acid substitutions associated with MBV resistance result in loss of its nucleolar localization when visualized after transient transfection, whereas substitutions representing normal interstrain polymorphism had no such effect.