Cross-talk between tissues is critical for intergenerational acclimation to environmental change in Acanthochromis polyacanthus.

Organisms' responses to environmental changes involve complex, coordinated responses of multiple tissues and potential parental influences. Here using a multi-tissue approach we determine how variation in parental behavioural tolerance and exposure to elevated CO influences the developmental and intergenerational molecular responses of their offspring in the coral reef fish Acanthochromis polyacanthus to future ocean acidification (OA) conditions. Gills and liver showed the highest transcriptional response to OA in juvenile fish regardless of parental OA conditioning, while the brain and liver showed the greatest intergenerational acclimation signals.

Molecular basis of parental contributions to the behavioural tolerance of elevated pCO in a coral reef fish.

Knowledge of adaptive potential is crucial to predicting the impacts of ocean acidification (OA) on marine organisms. In the spiny damselfish, , individual variation in behavioural tolerance to elevated pCO has been observed and is associated with offspring gene expression patterns in the brain. However, the maternal and paternal contributions of this variation are unknown.

Elevated CO affects anxiety but not a range of other behaviours in juvenile yellowtail kingfish.

Elevated seawater CO can cause a range of behavioural impairments in marine fishes. However, most studies to date have been conducted on small benthic species and very little is known about how higher oceanic CO levels could affect the behaviour of large pelagic species. Here, we tested the effects of elevated CO, and where possible the interacting effects of high temperature, on a range of ecologically important behaviours (anxiety, routine activity, behavioural lateralization and visual acuity) in juvenile yellowtail kingfish, Seriola lalandi.

Exposure to Crude Oil from the Oil Spill Impairs Oil Avoidance Behavior without Affecting Olfactory Physiology in Juvenile Mahi-Mahi ().

The understanding of the detection threshold and behavioral response of fishes in response to crude oil is critical to predicting the effects of oil spills on wild fish populations. The oil spill released approximately 4.9 million barrels of crude oil into the northern Gulf of Mexico in 2010, overlapping spatially and temporally with the habitat of many pelagic fish species.

Damsels in Distress: Oil Exposure Modifies Behavior and Olfaction in Bicolor Damselfish ().

In fishes, olfactory cues evoke behavioral responses that are crucial to survival; however, the receptors, olfactory sensory neurons, are directly exposed to the environment and are susceptible to damage from aquatic contaminants. In 2010, 4.9 million barrels of crude oil were released into the northern Gulf of Mexico from the disaster, exposing marine organisms to this environmental contaminant.

Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics.

Understanding of T cell exhaustion and successful therapy to restore T cell function was first described using Clone (Cl) 13 variant selected from the lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) 53b parental strain. T cell exhaustion plays a pivotal role in both persistent infections and cancers of mice and humans. C57BL/6, BALB, SWR/J, A/J, 129, C3H, and all but one collaborative cross (CC) mouse strain following Cl 13 infection have immunosuppressed T cell responses, high PD-1, and viral titers leading to persistent infection and normal life spans.

An interplay between plasticity and parental phenotype determines impacts of ocean acidification on a reef fish.

The impacts of ocean acidification will depend on the ability of marine organisms to tolerate, acclimate and eventually adapt to changes in ocean chemistry. Here, we use a unique transgenerational experiment to determine the molecular response of a coral reef fish to short-term, developmental and transgenerational exposure to elevated CO, and to test how these responses are influenced by variations in tolerance to elevated CO exhibited by the parents. Within-generation responses in gene expression to end-of-century predicted CO levels indicate that a self-amplifying cycle in GABAergic neurotransmission is triggered, explaining previously reported neurological and behavioural impairments.

Heritability of behavioural tolerance to high CO in a coral reef fish is masked by nonadaptive phenotypic plasticity.

Previous studies have demonstrated limited potential for acclimation of adversely affected olfactory behaviours in reef fishes under elevated CO , indicating that genetic adaptation will be required to maintain behavioural performance in the future. Adaptation depends on the presence of heritable phenotypic variation in the trait, which may differ between populations and environments. We used parent-offspring regressions to estimate the heritability () of variation in behavioural tolerance to high CO (754 μatm) in both field-collected and laboratory-reared families of .

Effects of elevated CO on predator avoidance behaviour by reef fishes is not altered by experimental test water.

Pioneering studies into the effects of elevated CO on the behaviour of reef fishes often tested high-CO reared fish using control water in the test arena. While subsequent studies using rearing treatment water (control or high CO) in the test arena have confirmed the effects of high CO on a range of reef fish behaviours, a further investigation into the use of different test water in the experimental arena is warranted. Here, we used a fully factorial design to test the effect of rearing treatment water (control or high CO) and experimental test water (control or high CO) on antipredator responses of larval reef fishes.

Type I interferon is a therapeutic target for virus-induced lethal vascular damage.

The outcome of a viral infection reflects the balance between virus virulence and host susceptibility. The clone 13 (Cl13) variant of lymphocytic choriomeningitis virus--a prototype of Old World arenaviruses closely related to Lassa fever virus--elicits in C57BL/6 and BALB/c mice abundant negative immunoregulatory molecules, associated with T-cell exhaustion, negligible T-cell-mediated injury, and high virus titers that persist. Conversely, here we report that in NZB mice, despite the efficient induction of immunoregulatory molecules and high viremia, Cl13 generated a robust cytotoxic T-cell response, resulting in thrombocytopenia, pulmonary endothelial cell loss, vascular leakage, and death within 6-8 d.

Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection.

Is the TAM receptor Axl a receptor for lymphocytic choriomeningitis virus?

A recent publication indicated that overexpression of Axl, a cellular receptor that negatively regulates Toll-like receptor signaling, enhanced the entry of viruses pseudotyped with the glycoprotein of lymphocytic choriomeningitis virus (LCMV) in vitro. In testing the biological relevance of these observations, we found differences in neither viral kinetics between LCMV infections of Axl(-/-) and wild-type mice nor T-cell responses prior to spontaneous viral clearance. Thus, Axl is not required for productive LCMV infection of mice.

Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes.

We quantified CD8 T cells needed to cause type 1 diabetes and studied the anatomy of the CD8 T cell/beta (β) cell interaction at the immunologic synapse. We used a transgenic model, in situ tetramer staining to distinguish antigen specific CD8 T cells from total T cells infiltrating islets and a variety of viral mutants selected for functional deletion(s) of various CD8 T cell epitopes. Twenty percent of CD8 T cells in the spleen were specific for all immunodominant and subdominant viral glycoprotein (GP) epitopes.

Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection.

TLR7 is an innate signaling receptor that recognizes single-stranded viral RNA and is activated by viruses that cause persistent infections. We show that TLR7 signaling dictates either clearance or establishment of life-long chronic infection by lymphocytic choriomeningitis virus (LCMV) Cl 13 but does not affect clearance of the acute LCMV Armstrong 53b strain. TLR7(-/-) mice infected with LCMV Cl 13 remained viremic throughout life from defects in the adaptive antiviral immune response-notably, diminished T cell function, exacerbated T cell exhaustion, decreased plasma cell maturation, and negligible antiviral antibody production.

CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection.

DNAM-1 gene-deficient (-/-) mice take significantly longer to clear an acute and persistent LCMV infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 -/- mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 -/- and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 -/- CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the persistent viral infection.

Point mutation in the glycoprotein of lymphocytic choriomeningitis virus is necessary for receptor binding, dendritic cell infection, and long-term persistence.

Arenaviruses are a major cause of hemorrhagic fevers endemic to Sub-Saharan Africa and South America, and thus a major public health and medical concern. The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is widely used as a model system for studying persistent and acute infections, as well as for gaining an understanding of mammalian immune function. When originally characterized three decades ago, the LCMV isolate, Armstrong, which causes an acute infection in adult mice, was found to differ from the LCMV Clone 13 strain that causes a persistent infection by two amino acid changes, one within the virus surface glycoprotein (GP1: F260L) and the other within the virus L polymerase (K1076Q).

RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis.

Measles virus (MV), a member of the family Paramyxoviridae and an exclusively human pathogen, is among the most infectious viruses. A progressive fatal neurodegenerative complication, subacute sclerosing panencephalitis (SSPE), occurs during persistent MV infection of the CNS and is associated with biased hypermutations of the viral genome. The observed hypermutations of A-to-G are consistent with conversions catalyzed by the adenosine deaminase acting on RNA (ADAR1).

Treatment with a sphingosine analog does not alter the outcome of a persistent virus infection.

There is no known antiviral drug treatment that routinely terminates persistent virus infections. A recent provocative report indicated that low dosage of the sphingosine analog FTY720 caused lymphopenia in mice persistently infected with lymphocytic choriomeningitis virus (LCMV)-clone 13 (Cl 13) and induced viral clearance within 30 days post-treatment (Premenko-Lanier et al., 2008).

In vivo conversion of BM plasmacytoid DC into CD11b+ conventional DC during virus infection.

DC are a highly heterogeneous population that plays a critical role in host defense. We previously demonstrated that virus infection induces BM plasmacytoid DC (pDC) differentiation into CD11b(+) conventional DC (cDC) upon in vitro culture with Fms-like tyrosine kinase 3 ligand (Flt3L). Here we use immunoglobulin D-J rearrangements and pDC adoptive transfer to provide definitive proof supporting BM pDC conversion into CD11b(+) cDC during in vivo viral infection.