Platelet-mediated replication and translation of DENV RNA. Highlighted are aspects of the DENV-platelet interaction directly measured and implied by the current study. Through DC-SIGN and HSP on the platelet surface, DENV is internalized, presumably by an endocytic process similar to other cells. The (+)ssRNA virus genome is released from the nucleocapsid into the cytosol where it is translated to produce a polyprotein by ribosomes on the rough endoplasmic reticulum or function as a replication template for NS5. NS5 must be released from the polyprotein by unknown platelet proteases or the DENV-encoded protease NS2B/NS3 complex. The mature NS1 antigen was followed directly, which may explain the presence of cross-reactive platelet antibodies in patients following DENV infection. Platelets have mitochondria to facilitate the energy-demanding replication and translational processes and remnants of Golgi apparatus, where progeny DENV virions may be assembled.