Drought response strategies are coupled with leaf habit in 35 evergreen and deciduous oak (Quercus) species across a climatic gradient in the Americas.

Distinct survival strategies can result from trade-offs in plant function under contrasting environments. Investment in drought resistance mechanisms can enhance survivorship but result in conservative growth. We tested the hypothesis that the widespread oaks (Quercus spp.

Generating West Nile Virus from an Infectious Clone.

WNV infectious clones are valuable tools for elucidating WNV biology. Nevertheless, relatively few infectious WNV clones have been generated because their construction is hampered by the instability of flaviviral genomes. More recently, advances in cloning techniques as well as the development of several two-plasmid WNV infectious clone systems have facilitated the generation of WNV infectious clones.

Hepatitis E virus inhibits type I interferon induction by ORF1 products.

Hepatitis E virus (HEV) causes both endemic and epidemic human hepatitis by fecal-oral transmission in many parts of the world. Zoonotic transmission of HEV from animals to humans has been reported. Due to the lack of an efficient cell culture system, the molecular mechanisms of HEV infection remain largely unknown.

In vitro and in vivo characterization of a West Nile virus MAD78 infectious clone.

The viral determinants governing the varied neuropathogenicity of different West Nile virus (WNV) strains are poorly understood. Here, we generated an infectious clone (WNV-MAD(IC)) of the non-pathogenic strain WNV-MAD78 and compared its replication to that of parental WNV-MAD78 and a WNV-MAD78 infectious clone (WNV-MAD(TX-UTRs)) containing the 5' and 3' untranslated regions (UTRs) of the pathogenic strain WNV-TX. All three viruses replicated at similar rates and caused similar lethality in mice.

Structural proteins of West Nile virus are a major determinant of infectious particle production and fitness in astrocytes.

The molecular basis for the increased resistance of astrocytes to a non-neuropathogenic strain of West Nile virus (WNV), WNV-MAD78, compared with the neuropathogenic strain WNV-NY remains unclear. Here, we demonstrated that the reduced susceptibility of astrocytes to WNV-MAD78 is due to a combination of both cellular activities as well as viral determinants. Analyses of the viral particle indicated that astrocyte-derived WNV-MAD78 particles were less infectious than those of WNV-NY.

Enhancement of interferon induction by ORF3 product of hepatitis E virus.

Unlabelled: Hepatitis E virus (HEV) causes both the endemic and epidemic spread of acute hepatitis in many parts of the world. HEV open reading frame 3 (ORF3) encodes a 13-kDa multifunctional protein (vp13) that is essential for HEV infection of animals. The exact role of vp13 in HEV infection remains unclear.

Generation of West Nile virus infectious clones containing amino acid insertions between capsid and capsid anchor.

West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3' untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides.

IFN-dependent and -independent reduction in West Nile virus infectivity in human dermal fibroblasts.

Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, we demonstrate that neuroinvasive, WNV-New York (WNV-NY), and nonneuroinvasive, WNV-Australia (WNV-AUS60) strains are able to infect and replicate in primary human dermal fibroblasts (HDFs). However, WNV-AUS60 replication and spread within HDFs was reduced compared to that of WNV-NY due to an interferon (IFN)-independent reduction in viral infectivity early in infection.

Differential induction of CCL5 by pathogenic and non-pathogenic strains of West Nile virus in brain endothelial cells and astrocytes.

The neuroinflammatory response to West Nile virus (WNV) infection can be either protective or pathological depending on the context. Although several studies have examined chemokine profiles within brains of WNV-infected mice, little is known about how various cell types within the central nervous system (CNS) contribute to chemokine expression. Here, we assessed chemokine expression in brain microvascular endothelial cells and astrocytes, which comprise the major components of the blood-brain barrier (BBB), in response to a non-pathogenic (WNV-MAD78) and a highly pathogenic (WNV-NY) strain of WNV.

The neuroimmune response to West Nile virus.

The recent introduction of highly pathogenic strains of West Nile virus (WNV) into naïve populations in Europe, Israel, and the USA has resulted in a marked increase in both the number of reported cases and the severity of disease compared to previous outbreaks. The impact of the increased virulence of recently emerged strains of WNV is exacerbated by the fact that antiviral therapies and vaccines are not currently available for use in humans. A greater understanding of the viral and host factors involved in WNV-mediated neuropathology is necessary to facilitate the development of novel therapeutic approaches.

Differential replication of pathogenic and nonpathogenic strains of West Nile virus within astrocytes.

The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells, which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY.

West Nile virus (WNV) replication is independent of autophagy in mammalian cells.

Autophagy is a homeostatic process responsible for recycling cytosolic proteins and organelles. Moreover, this pathway contributes to the cell's intrinsic innate defenses. While many viruses have evolved mechanisms to antagonize the antiviral effects of the autophagy pathway, others subvert autophagy to facilitate replication.

Identification of multiple RIG-I-specific pathogen associated molecular patterns within the West Nile virus genome and antigenome.

The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. One of the strategies utilized by West Nile virus (WNV) to circumvent the host response is to evade detection by the pathogen recognition receptor RIG-I early in infection. To begin elucidating the mechanisms by which WNV eludes detection, we undertook a systematic analysis of the WNV genome and antigenome to identify RIG-I-specific pathogen associated molecular patterns (PAMPs).

Antiviral drug research proposal activity.

The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology.

A model for using a concept inventory as a tool for students' assessment and faculty professional development.

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006.

How flaviviruses activate and suppress the interferon response.

The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection.

Assessing student understanding of host pathogen interactions using a concept inventory.

As a group of faculty with expertise and research programs in the area of host-pathogen interactions (HPI), we are concentrating on students' learning of HPI concepts. As such we developed a concept inventory to measure level of understanding relative to HPI after the completion of a set of microbiology courses (presently eight courses). Concept inventories have been useful tools for assessing student learning, and our interest was to develop such a tool to measure student learning progression in our microbiology courses.

Thresholds for sampled sloan letters are smaller than sample spacing.

Purpose: Although the effect of spatial sampling on the visibility of grating stimuli is well described and well understood, little research has been conducted into the effects of spatial sampling on the visibility of letter optotypes. The purpose of this study was to investigate whether thresholds for spatially sampled Sloan letters were equal to or significantly smaller than the spacing between spatial samples.

Methods: For four visually normal subjects, we measured Sloan letter acuity thresholds, presented on a computer monitor, after the letters had been sampled by sampling arrays with 6.

A virocidal amphipathic {alpha}-helical peptide that inhibits hepatitis C virus infection in vitro.

An amphipathic alpha-helical peptide (C5A) derived from the membrane anchor domain of the hepatitis C virus (HCV) NS5A protein is virocidal for HCV at submicromolar concentrations in vitro. C5A prevents de novo HCV infection and suppresses ongoing infection by inactivating both extra- and intracellular infectious particles, and it is nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity. Mutational analysis indicates that C5A's amphipathic alpha-helical structure is necessary but not sufficient for its virocidal activity, which depends on its amino acid composition but not its primary sequence or chirality.

Establishment and maintenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1.

RIG-I and MDA5, two related pathogen recognition receptors (PRRs), are known to be required for sensing various RNA viruses. Here we investigated the roles that RIG-I and MDA5 play in eliciting the antiviral response to West Nile virus (WNV). Functional genomics analysis of WNV-infected fibroblasts from wild-type mice and RIG-I null mice revealed that the normal antiviral response to this virus occurs in two distinct waves.

Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence.

The emergence of West Nile virus (WNV) in the Western Hemisphere is marked by the spread of pathogenic lineage I strains, which differ from typically avirulent lineage II strains. To begin to understand the virus-host interactions that may influence the phenotypic properties of divergent lineage I and II viruses, we compared the genetic, pathogenic, and alpha/beta interferon (IFN-alpha/beta)-regulatory properties of a lineage II isolate from Madagascar (MAD78) with those of a new lineage I isolate from Texas (TX02). Full genome sequence analysis revealed that MAD78 clustered, albeit distantly, with other lineage II strains, while TX02 clustered with emergent North American isolates, more specifically with other Texas strains.

West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling.

The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. We have previously shown that West Nile virus NY (WNV-NY) delays activation of interferon regulatory factor 3 (IRF-3), a transcription factor critical to the initiation of the antiviral response. Here we demonstrate that the delayed activation of IRF-3 is essential for WNV-NY to achieve maximum virus production.

The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway.

Recent outbreaks of West Nile Virus (WNV) have been associated with an increase in morbidity and mortality in humans, birds, and many other species. We have initiated studies to define the molecular mechanisms by which a recent pathogenic isolate of WNV evades the host cell innate antiviral response. Biochemical and microarray analyses demonstrated that WNV induced the expression of beta interferon (IFN-beta) and several IFN-stimulated genes late in infection of cultured human cells.

Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus.

Productive entry of human immunodeficiency virus type 1 (HIV-1) into a host cell is believed to proceed via fusion of the viral envelope with the host cell's plasma membrane. Interestingly, the majority of HIV-1 particles that bind to the cell surface are taken up by the host cell via endocytosis; however, this mode of internalization generally does not result in infection. Presumably, virus particles remain trapped in the endocytic pathway and are eventually degraded.