Human cytomegalovirus microRNA miR-US4-1 inhibits CD8+ T cell responses by targeting the aminopeptidase ERAP1

The major histocompatibility complex (MHC) class I molecules present peptides on the cell surface by CD8(+) T cells, which is critical for killing of virally infected or transformed cells. Precursors of MHC class I-presented peptides are trimmed to mature epitopes by endoplasmic reticulum aminopeptidase 1 (ERAP1). The US2-US11 genomic region of human cytomegalovirus (HCMV) is dispensable for viral replication and harbors 3 microRNAs (miRNAs). We show here the HCMV miR-US4-1 specifically down-regulates ERAP1 expression during viral infection. Accordingly, the trimming of HCMV-derived peptides is inhibited, leading to reduced susceptibility of infected cells to HCMV-specific cytotoxic T lymphocytes (CTLs). Our findings reveal a novel viral miRNA-based CTL evasion mechanism that targets a key step in the MHC class I antigen-processing pathway

Adhesion to the extracellular matrix is positively regulated by retinoic acid in HepG2 cells

Aims: In this work, we aimed to investigate the possible modulation of cell–matrix interactions by retinoic acid (RA), in view of the well-known role of the extracellular matrix (ECM) and integrins in hepatocyte differentiation and proliferation. For this purpose, we analysed the adhesion ability of HepG2 cells on different substrates in the presence and absence of RA evaluating both the expression and cellular localisation of major proteins involved in focal contacts, using Western blot and confocal microscopy. Results: A positive and substratedependent effect of RA on cell–matrix adhesion was observed after long-term culture. The increased adhesiveness in the treated cells was accompanied by an enhanced expression of b1 and a3 integrin subunits, together with a redistribution of b1 receptors clustered at the basal surface. In contrast, the levels of focal adhesion kinase (FAK), paxillin and a-actinin were unchanged, as was the phosphorylation state of FAK. Nonetheless, a stronger association between b1 integrin and intracytoplasmatic proteins of focal contacts was observed in coimmunoprecipitation experiments after RA treatment, suggesting improved connection with the actin cytoskeleton.These results are consistent with previously described antiproliferative and differentiative effects of RA on transformed hepatocytes, and confirm the hypothesis of a direct influence of RA on specific adhesion molecules

THE CHANGING NATURE OF RURAL AMERICA-super-1

Rural regions are changing, both in terms of economic dispersal and population patterns. Rural growth is attributed to technological innovation, improving capacity to deal with impending problems as well as improving quality of life, and intercommunity linkage. For some communities, this means the prospects of indigenous economic development. Copyright 1982 by The Policy Studies Organization.