Classically, the cytidine deaminase APOBEC3G (A3G) exerts antiviral activity against transposable elements, retroviruses, and hepatitis B virus.
More...Classically, the cytidine deaminase APOBEC3G (A3G) exerts antiviral activity against transposable elements, retroviruses, and hepatitis B virus. However, we found earlier, that it also inhibits measles (MV), mumps (MuV) and respiratory syncytial virus (RSV), but the mechanism of inhibition remained unclear. Because A3G is present in RNA processing (P) bodies, where it is involved in the regulation of mRNA decay, we supposed that it may influence the expression of host cell factors, some of which may affect viral replication. Using a microarray we therefore assessed in Vero cells whether A3G expression influences the cellular gene expression. We found alterations indicating 844 up-regulated and 598 down-regulated transcripts (adjusted P values < 0.05). Of these trancripts 19 were up-regulated and 23 down-regulated by a factor of > 2. One of the down-regulated factors, MOSC2, appeared to support MV replication, since shRNA-mediated MOSC2 knock down reduced MV replication. In addition, two up-regulated factors, REDD1 and KDELR2, impaired MV replication when over-expressed in VeroREDD1 is a cellular inhibitor of mTORC1, a regulator of cellular homeostasis controlling cell growth and protein synthesis. Rapamycin also reduced MV replication confirming our findings with REDD1. The KDELR2 retains chaperons in the ER, which are required for proper folding and transport of MV glycoproteins to the cell surface, and thereby reduces MV glycoprotein expression at the cell surface, syncytium formation, and the formation of infectious virus.
Overall design: Comparison of transcript expression between Vero (Vero-023) and A3G-expressing Vero (Vero-024-2) cells. The effects of altered gene expression on MV infection were evaluated.
Less...