Silkworm SOCS2 Differentially Promotes Multiple Steps of BmNPV Proliferation and Modulates the mRNA Expression of SOCS-STAT Network Components.

Suppressors of cytokine signaling (SOCSs) are negative feedback regulators of the JAK-STAT pathway and are often exploited by viruses to evade host antiviral immunity. Unlike other SOCS members, the role of SOCS2 in viral infection remains poorly understood. Here, we report that overexpression of silkworm SOCS2 isoforms, SOCS2L and SOCS2S, promotes Bombyx mori nucleopolyhedrovirus (BmNPV) replication at multiple stages, including viral DNA replication, late gene (VP39) transcription, and virion egress, while their knockdown suppresses these processes. Overexpression of SH2 domain mutants (R123Q in SOCS2S, R142Q in SOCS2L) reduced viral DNA replication to baseline and VP39 expression below baseline, drastically decreased infectious progeny titers, but unexpectedly increased viral DNA release to wild-type levels, suggesting that the SH2 domain may differentially regulate distinct steps of viral replication. Furthermore, SOCS2 isoforms, alone or cooperatively with BmNPV, modulate the mRNA levels of SOCS-STAT network members in an isoform-, dose-, and target-specific manner. Collectively, this study reveals for the first time the multiple proviral functions of silkworm SOCS2 isoforms, with differential effects on distinct stages of the viral life cycle, and highlights their potential as transcriptional modulators exploited by viruses for immune evasion.