H11/HspB8 and Its Herpes Simplex Virus Type 2 Homologue ICP10PK Share Functions That Regulate Cell Life/Death Decisions and Human Disease
Figure 2
The ICP10PK vector ΔRR inhibits UPR. (a) mSOD1 (G93A) transgenic rats were treated with ΔRR (107 pfu; 100 μL) or an equal volume of PBS in both hind limbs by intramuscular injection beginning at age of 85 days. The ΔRR-treated G93A rats lived significantly longer than their PBS-treated counterparts with a median survival of 195 and 154 days, respectively ( by log-rank Mantel-Cox analysis). Serial sections from the L4-L5 region collected on day 153 were stained in double immunofluorescence with antibodies to human SOD1 (Alexa Fluor 488 conjugated secondary antibody; green) and CHOP (Alexa Fluor 594 conjugated secondary antibody; red). DAPI nuclear staining is blue. Only the PBS treated animals showed evidence of aggregates containing CHOP and mSOD1 co-localization. Scale bar = 10 μm. (b). Neuronally differentiated N2a cells that were stably transfected with another mSOD1 mutant (G85R) were mock infected with PBS or infected with ΔRR or a vector that lacks ICP10PK (ΔPK) and treated with H2O2 (100 μM; 2 hrs) to induce oxidative stress. N2a cells stably transfected with the wt SOD1 were studied in parallel and served as control. At 24 hrs after infection the cells were stained by double immunofluorescence with Alexa Fluor 594 conjugated SOD1 antibody (red) and Alexa Fluor 488 conjugated pp38MAPK antibody (green). DAPI nuclear stain is in blue. Scale bar = 10 μm. Aggregates are not seen in the ΔRR-treated cells, associated with the inhibition of p38MAPK phosphorylation (activation).
