The role of hemocytes in the control of viral replication and disease in vivo. Javier Robalino, Louisa Wu. Institute for Bioscience and Biotechnology Research, Dept. of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.

   Several pathways have been implicated in the innate antiviral response of flies, including RNAi, autophagy, JAK/STAT, Toll, and Imd signaling. Apart from RNAi, for which the mechanisms of action are well understood, the ways in which these other immune pathways participate in the control of viral replication remain largely unknown. Moreover, in flies and other invertebrates, the contributions of specific cell types to the antiviral response at an organismal level have remained mostly unexplored. We show that plasmatocytes, the major hemocyte type in the adult fly, effectively and preferentially internalize Drosophila X Virus (DXV) particles introduced into the hemolymph, and their role in this context is to restrict the replication of the virus. In spite of avidly capturing virus from circulation, hemocytes are not a major site of viral replication in vivo, and decreasing the number of viable hemocytes by targeted cell ablation leads to increased susceptibility to viral infection. This organismal level, hemocyte-mediated antiviral protection, critically requires the beta subunit of the Signal Recognition Particle Receptor (SRPRB). Down-regulation of SRPRB leads to uncontrolled DXV replication within hemocytes, and this is sufficient for a dramatic increase in the susceptibility of the fly to infection with this virus. Surprisingly, down-regulation in hemocytes of several of the subunits of the Signal Recognition Particle (SRP) and of the Sec61 translocon, which act upstream and downstream, respectively, of the SRP receptor during protein translocation into the ER, do not cause increased viral replication. We hypothesize a unique role for SRPRB in the ability of hemocytes to restrict viral replication, a role that is likely independent of its canonical function in co-translational targeting of membrane and secreted proteins.