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Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-[alpha]/[beta] induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-[beta] protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. [Tlr3.sup.-/-] mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-[beta] secretion and ISG mRNA in induced pluripotent stem cell-derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-[beta] immunity., Introduction TLR3 on endosomes recognizes double-stranded RNA (dsRNA) intermediates or by-products generated during viral infection. TLR3 signaling leads to the activation of IFN regulatory factor 3 (IRF3), NF-[kappa]B, and ATF/c-jun, [...]

Biomass burning plumes are frequently transported over the Southeast Atlantic stratocumulus deck during the southern African fire season (June-October). The plumes bring large amounts of absorbing aerosols as well as enhanced moisture, which can trigger a rich set of aerosol-cloud-radiation interactions with climatic consequences that are still poorly understood. We use large-eddy simulation (LES) to explore and disentangle the individual impacts of aerosols and moisture on the underlying stratocumulus clouds, the marine boundary layer (MBL) evolution and the stratocumulus to cumulus transition (SCT) for three different meteorological situations over the Southeast Atlantic during August 2017. For all three cases, our LES shows that the SCT is driven by increased sea surface temperatures and cloud-top entrainment as the air is advected towards the equator. In the LES model, aerosol indirect effects, including impacts on drizzle production, have a small influence on the modeled cloud evolution and SCT, even when aerosol concentrations are lowered to background concentrations. In contrast, local semi-direct effects, i.e aerosol absorption of solar radiation in the MBL, causes a reduction in cloud cover that can lead to a speed-up of the SCT, in particular during daytime and during broken cloud conditions, especially in highly polluted situations. The largest impact on the radiative budget comes from aerosol impacts on cloud albedo; the plume with absorbing aerosols produces a total average net radiative cooling effect between -4 and -9 Wm-2 over the three days of simulations. We find that the moisture accompanying the aerosol plume produces an additional cooling effect that is about as large as the total aerosol radiative effect. Overall, there is still a large uncertainty associated with the radiative and cloud evolution effects of biomass burning aerosols. A comparison between different models in a common framework, combined with constraints from in-situ observations, could help to reduce the uncertainty. [ABSTRACT FROM AUTHOR]

Biomass burning plumes are frequently transported over the Southeast Atlantic stratocumulus deck during the southern African fire season (June–October). The plumes bring large amounts of absorbing aerosols as well as enhanced moisture, which can trigger a rich set of aerosol-cloud-radiation interactions with climatic consequences that are still poorly understood. We use large-eddy simulation (LES) to explore and disentangle the individual impacts of aerosols and moisture on the underlying stratocumulus clouds, the marine boundary layer (MBL) evolution and the stratocumulus to cumulus transition (SCT) for three different meteorological situations over the Southeast Atlantic during August 2017. For all three cases, our LES shows that the SCT is driven by increased sea surface temperatures and cloud-top entrainment as the air is advected towards the equator. In the LES model, aerosol indirect effects, including impacts on drizzle production, have a small influence on the modeled cloud evolution and SCT, even when aerosol concentrations are lowered to background concentrations. In contrast, local semi-direct effects, i.e aerosol absorption of solar radiation in the MBL, causes a reduction in cloud cover that can lead to a speed-up of the SCT, in particular during daytime and during broken cloud conditions, especially in highly polluted situations. The largest impact on the radiative budget comes from aerosol impacts on cloud albedo; the plume with absorbing aerosols produces a total average net radiative cooling effect between -4 and -9 W m -2 over the three days of simulations. We find that the moisture accompanying the aerosol plume produces an additional cooling effect that is about as large as the total aerosol radiative effect. Overall, there is still a large uncertainty associated with the radiative and cloud evolution effects of biomass burning aerosols. A comparison between different models in a common framework, combined with constraints from in-situ observations, could help to reduce the uncertainty. [ABSTRACT FROM AUTHOR]