The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor B (NF-B). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-B binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.

The cellular microRNA miR-155 has been shown to be involved in lymphocyte activation and is expressed in

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The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.

Harpin proteins from gram-negative plant-pathogenic bacteria can stimulate hypersensitive cell death (HCD) and pathogen defense as well as enhance growth in plants. Two of these diverse activities clearly are beneficial and may depend on particular functional regions of the proteins. Identification of beneficial and deleterious regions might facilitate the beneficial use of harpin-related proteins on crops without causing negative effects like cell death. Here, we report the identification and testing of nine functional fragments of HpaG(Xooc), a 137-amino-acid harpin protein from Xanthomonas oryzae pv. oryzicola, the pathogen that causes bacterial leaf streak of rice. Polymerase chain reaction-based mutagenesis generated nine proteinaceous fragments of HpaG(Xooc); these caused different responses following their application to Nicotiana tabacum (tobacco) and Oryza sativa (rice). Fragment HpaG62-137, which spans the indicated amino acid residues of the HpaG, induced more intense HCD; in contrast, HpaG10-42 did not cause evident cell death in tobacco. However, both fragments stimulated stronger defense responses and enhanced more growth in rice than the full-length parent protein, HpaG(Xooc). Of the nine fragments, the parent protein and one deletion mutant of HpaG(Xooc) tested, HpaG10-42, stimulated higher levels of rice growth and resulted in greater levels of resistance to X. oryzae pv. oryzae and Magnaporthe grisea. These pathogens cause bacterial leaf blight and rice blast, respectively, the two most important diseases of rice world-wide. HpaG10-42 was more active than HpaG(Xooc) in inducing expression of several genes that regulate rice defense and growth processes and activating certain signaling pathways, which may explain the greater beneficial effects observed from treatment with that fragment. Overall, our results suggest that HpaG10-42 holds promise for practical agricultural use to induce disease resistance and enhance growth of rice.