138 research outputs found
In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis
Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidineβ5βcarbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ highβresolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively
Stable expression of clonal specificity in murine cytomegalovirus-specific large granular lymphoblast lines propagated long-term in recombinant interleukin 2.
Heterocellular induction of interferon by negative-sense RNA viruses
The infection of cells by RNA viruses is associated with the recognition of virus PAMPs (pathogen-associated molecular patterns) and the production of type I interferon (IFN). To counter this, most, if not all, RNA viruses encode antagonists of the IFN system. Here we present data on the dynamics of IFN production and response during developing infections by paramyxoviruses, influenza A virus and bunyamwera virus. We show that only a limited number of infected cells are responsible for the production of IFN, and that this heterocellular production is a feature of the infecting virus as opposed to an intrinsic property of the cells
Innate and Adaptive Immune Responses to Herpes Simplex Virus
Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in vitro and in vivo. Cell types such as NK cells and pDCs contribute to innate anti-HSV responses in vivo. Finally, the adaptive response includes both humoral and cellular components that play important roles in antiviral control and latency. This review summarizes the innate and adaptive effectors that contribute to susceptibility, immune control and pathogenesis of HSV, and highlights the delicate interplay between these two important arms of immunity
Stochastic Expression of the Interferon-Ξ² Gene
The analysis of stochastic interferon-beta gene expression in virus-infected mammalian cells reveals that the levels of components required for virtually every step in the virus induction pathway are limiting
Bioluminescent Imaging Reveals Divergent Viral Pathogenesis in Two Strains of Stat1-Deficient Mice, and in Ξ±ΓΞ³ Interferon Receptor-Deficient Mice
Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factor signal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat1β/β and IFNΞ±ΓΞ³Rβ/β mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat1β/β mice and in IFNΞ±ΓΞ³Rβ/β mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat1β/β (N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day 10 post-infection. In stark contrast, infection of IFNΞ±ΓΞ³Rβ/β mice was rapidly fatal, with associated viremia and fulminant infection of the liver and spleen, with infected infiltrating cells being primarily of the monocyte/macrophage lineage. To resolve the surprising difference between Stat1β/β and IFNΞ±ΓΞ³Rβ/β mice, we infected an additional Stat1β/β strain deleted in the DNA-binding domain (129Stat1β/β (DBD)). These 129Stat1β/β (DBD) mice recapitulated the lethal pattern of liver and spleen infection seen following infection of IFNΞ±ΓΞ³Rβ/β mice. This lethal pattern was also observed when 129Stat1β/β (N-term) mice were infected and treated with a Type I IFN-blocking antibody, and immune cells derived from 129Stat1β/β (N-term) mice were shown to be responsive to Type I IFN. These data therefore show significant differences in viral pathogenesis between two commonly-used Stat1β/β mouse strains. The data are consistent with the hypothesis that Stat1β/β (N-term) mice have residual Type I IFN receptor-dependent IFN responses. Complete loss of IFN signaling pathways allows viremia and rapid viral spread with a fatal infection of the liver. This study underscores the importance of careful comparisons between knockout mouse strains in viral pathogenesis, and may also be relevant to the causation of HSV hepatitis in humans, a rare but frequently fatal infection
Resistance of nude mice to herpes simplex virus and correlation with in vitro production of interferon.
Interferon production in the murine mixed lymphocyte culture. I. Interferon production caused by differences in the h-2k and h-2d region but not by differences in the i region of the m locus.
- β¦