Role of microRNAs in host defense against porcine reproductive and respiratory syndrome virus infection: a hidden front line

MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.

The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated. Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3' untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3' untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions. We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.

To estimate the annual cost of infections attributable to porcine reproductive and respiratory syndrome (PRRS) virus to US swine producers. Economic analysis. Data on the health and productivity of PRRS-affected and PRRS-unaffected breeding herds and growing-pig populations were collected from a convenience sample of swine farms in the midwestern United States. Health and productivity variables of PRRS-affected and PRRS-unaffected swine farms were analyzed to estimate the impact of PRRS on specific farms. National estimates of PRRS incidence were then used to determine the annual economic impact of PRRS on US swine producers. PRRS affected breeding herds and growing-pig populations as measured by a decrease in reproductive health, an increase in deaths, and reductions in the rate and efficiency of growth. Total annual economic impact of these effects on US swine producers was estimated at dollar 66.75 million in breeding herds and dollar 493.57 million in growing-pig populations. PRRS imposes a substantial financial burden on US swine producers and causes approximately dollar 560.32 million in losses each year. By comparison, prior to eradication, annual losses attributable to classical swine fever (hog cholera) and pseudorabies were estimated at dollar 364.09 million and dollar 36.27 million, respectively (adjusted on the basis of year 2004 dollars). Current PRRS control strategies are not predictably successful; thus, PRRS-associated losses will continue into the future. Research to improve our understanding of ecologic and epidemiologic characteristics of the PRRS virus and technologic advances (vaccines and diagnostic tests) to prevent clinical effects are warranted.