Semliki Forest virus strongly reduces mosquito host defence signaling

Abstract

The Alphavirus genus within the Togaviridae family contains several important mosquito-borne arboviruses. Other than the antiviral activity of RNAi, relatively little is known about alphavirus interactions with insect cell defences. Here we show that Semliki Forest virus (SFV) infection of Aedes albopictus-derived U4.4 mosquito cells reduces cellular gene expression. Activation prior to SFV infection of pathways involving STAT/IMD, but not Toll signaling reduced subsequent virus gene expression and RNA levels. These pathways are therefore not only able to mediate protective responses against bacteria but also arboviruses. However, SFV infection of mosquito cells did not result in activation of any of these pathways and suppressed their subsequent activation by other stimuli.

Advances in dissecting mosquito innate immune responses to arbovirus infection

“…We have recently reported that mild reduction of host gene expression also occurs in SFVinfected Ae. albopictus U4.4 cells (Fragkoudis et al, 2008). In this case, it also appears that host RNA synthesis is reduced early in infection (our unpublished observations).…”

“…In the case of another alphavirus, SFV, if activated before infection, not Toll-but Gram-negative-mediated signalling (JAK/STAT or Imd/Jnk) can inhibit virus replication in mosquito cell cultures (Fragkoudis et al, 2008). Bacterial infection also induces resistance to various RNA viruses in D. melanogaster, whilst the JAK/STAT pathway is a mediator of antiviral activities (Dostert et al, 2005;Teixeira et al, 2008).…”

Antiviral responses of arthropod vectors: an update on recent advances

“…Activated STAT acts as a transcription factor inducing expression of antimicrobial peptides (AMPs) such as two DENV restriction factors [115] and vir-1 [92]. However, treatment with poly I:C (a synthetic analogue of dsRNA) or BTV dsRNA did not lead to vago upregulation and STAT activation in C. quinquefasciatus cells [92], and infection of U4.4 cells with the alphavirus SFV did not lead to activation of STAT [33]. Taken together, these findings suggest that activation of STAT may be a specific anti-flaviviral response.…”

“…Taken together, these findings suggest that activation of STAT may be a specific anti-flaviviral response. However, replication of SFV was reduced when STAT was activated prior to SFV infection by treatment with heat-inactivated Escherichia coli bacteria [33]. Due to the concurrent activation of the Imd pathway, it could not be concluded if this was a specific consequence of JAK/STAT activation.…”

“…SINV replication in D. melanogaster resulted in increased expression of components of the Imd pathway and the downstream gene diptericin-B has antiviral activity against SINV [50]. Preactivation of the Imd pathway by heat-inactivated E. coli also increased SFV replication in U4.4 cells [33]. In the mosquito A. gambiae, ONNV infection led to changes in expression of Imd pathway components, possibly activating the Imd pathway, but since knockdown of REL2 gene expression did not affect virus production, the role of Imd in ONNV infection remains unclear [125].…”