Fig. 6. Adaptive stimulation of telomerase activity by the virus OsHV-1.

(A) Telomerase activity increased in offspring surviving viral challenge (n = 72 familial pools of 10 individuals per pool), and this response is mitigated in those from old parents. (B) We used genome annotation of C. gigas (42) to explore telomerase gene expression in response to OsHV-1, obtained from previously published RNA-seq projects (30, 33, 43) including the constitutive telomerase reverse transcriptase (TERT) and the accessory proteins [Tric1, TCAB, NPH2, NOP10, GAR1, TEP1, TIAR, and HSP90; see (25)]. (C) At the baseline state, TERT expression discriminates oyster lineages experimentally selected for their resistance or susceptibility to OsHV-1 (30, 43) (**P = 0.007). (D) In response to viral exposition, all telomerase genes but one (TEP 1) covaried together along a main axis of a principal components analysis (PCA) and inversely with TERT expression (fig. S7). Extracting normalized scores (PC1) for each experimental replicate, we identified a quadratic trend with response peaking at 24 to 48 hours after infection (time: F_1,48 = 46.0, P < 0.001; time²: F_1,48 = 50.8, P < 0.001). Peak intensity was specific both to family types (susceptible and resistant at 21°C) and acclimation temperature (unselected families at 21° or 29°C). Gene expression trends paralleled the associated mortality rates. In other words, inhibition of TERT gene expression was similar between families selected for susceptibility and unselected families acclimated 21°C (pairwise post hoc: t = −0.02, P > 0.999). Inhibition of TERT was lower in surviving than susceptible oysters (all pairwise post hoc: |t| > 4.2, P < 0.001) and similar between in resistant and among oysters conditioned to 29°C (pairwise post hoc: t = −0.1, P > 0.999).