In order to better understand the mechanism by which MCMV evades the PKR response, we investigated the
SAHA molecular weight associations of pm142 and pm143 with each other and with PKR. Both pm142 and pm143 interact with PKR in infected and transfected cells. However, the similar to 200-kDa pm142-pm143 complex that forms in these cells does not contain substantial amounts of PKR, suggesting that the interactions between pm142-pm143 and PKR are unstable or transient. The stable, soluble pm142-pm143 complex appears to be a heterotetramer consisting of two molecules of pm142 associated with each other, and each one binds to and stabilizes a monomer of pm143. MCMV infection also causes relocalization of PKR into the nucleus and to an insoluble cytoplasmic compartment. These results suggest a model in which the pm142-pm143 multimer interacts with PKR and causes its sequestration in cellular compartments where it is unable to shut off translation and repress viral replication.”
“Administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to adult (2-month to 4-month-old) male C57BL/6 mice (MPTP-sensitive) is a valuable NF-��B inhibitor Parkinson’s disease model. At comparable age, other strains, such as BALB/c, are minimally
affected by MPTP (MPTP-resistant). However, the maintenance of resistance to MPTP throughout aging in MPTP-resistant strains has not been studied. Here, we show that, as previously reported, 1-month and 18-month-old C57BL/6 mice are least and most sensitive to MPTP, respectively. MPTP as expected, did not affect the younger (1-month and 3-month-old) BALB/c mice, but it markedly decreased striatal dopamine in the older (10-month and 18-month-old) BALB/c mice. These data suggest that the sensitivity to MPTP is age dependent and that mice from an MPTP-resistant strain lose their resistance
NADPH-cytochrome-c2 reductase as they age. NeuroReport 20:713-717 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“The leader proteinase (L(pro)) of foot-and-mouth disease virus (FMDV) is involved in antagonizing the innate immune response by blocking the expression of interferon (IFN) and by reducing the immediate-early induction of IFN-beta mRNA and IFN-stimulated genes. In addition to its role in shutting off cap-dependent host mRNA translation, L(pro) is associated with the degradation of the p65/RelA subunit of nuclear factor kappa B (NF-kappa B). Bioinformatics analysis suggests that L(pro) contains a SAP (for SAF-A/B, Acinus, and PIAS) domain, a protein structure associated in some cases with the nuclear retention of molecules involved in transcriptional control. We have introduced a single or a double mutation in conserved amino acid residues contained within this domain of L(pro). Although three stable mutant viruses were obtained, only the double mutant displayed an attenuated phenotype in cell culture. Indirect immunofluorescence analysis showed that L(pro) subcellular distribution is altered in cells infected with the double mutant virus.