Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus

Observation impact over the southern polar area during the Concordiasi field campaign

International audienceThe impact of observations on analysis uncertainty and forecast performance was investigated for austral spring 2010 over the southern polar area for four different systems (NRL, GMAO, ECMWF and Météo-France) at the time of the Concordiasi field experiment. The largest multi-model variance in 500 hPa height analyses is found in the southern sub-Antarctic oceanic region, where there are rapidly evolving weather systems, rapid forecast-error growth, and fewer upper-air wind observation data to constrain the analyses. The total impact of all observations on the model forecast was computed using the 24 h forecast sensitivity-to-observations diagnostic. Observation types that contribute most to the reduction of the forecast error are shown to be AMSU, IASI, AIRS, GPS-RO, radiosonde, surface and atmospheric motion vector observations. For sounding data, radiosondes and dropsondes, one can note a large impact on the analysis and forecasts of temperature at low levels and a large impact of wind at high levels. Observing system experiments using the Concordiasi dropsondes show a large impact of the observations over the Antarctic plateau extending to lower latitudes with the forecast range, with the largest impact around 50-70 • S. These experiments indicate there is a potential benefit from using radiance data better over land and sea-ice and from innovative atmospheric motion vectors obtained from a combination of various satellites to fill the current data gaps and improve numerical weather prediction analyses in this region