Replication of not-known-vector flaviviruses in mosquito cells is restricted by intracellular host factors rather than by the viral envelope proteins.

Chimeric yellow fever virus 17D (YFV-17D) and dengue virus type 2 (DENV2) carrying the surface proteins of Modoc virus (MODV), a not-known-vector (NKV) flavivirus, replicated efficiently in mammalian (Vero-B) and mosquito (C6/36) cells, whereas MODV failed to replicate in mosquito cells. Transfection of C6/36 cells with MODV RNA did not result in virus replication; however, transfection of these mosquito cells with YFV-17D or DENV2 RNA did. The inability of NKV viruses (such as MODV) to infect and replicate in arthropod cells is thus not determined by the viral envelope, but by a post-entry event.