ER retention and subviral particle formation: Unusual properties of the retroviral envelope glycoprotein of foamy viruses.

摘要

Foamy viruses (FVs) are classified in the genus Retroviridae, but recent data have shown that they are not conventional retroviruses. Their replication is unique among this group and actually resembles, in some aspects, that of the reverse transcriptase-encoding hepadnaviruses such as hepatitis B virus (HBV). Notably, in their characteristics for particle budding and release, FVs are more similar to HBV than to typical retroviruses.; One similarity is that both HBV and FV assemble and bud intracellularly. In HBV, intracellular budding is the result of an endoplasmic reticulum retrieval signal (ERRS) located in the N-terminus of the Env protein, L, which causes L to be sorted to the ER. We hypothesized that a similar mechanism was directing intracellular budding of FV and discovered the well-described dilysine motif (KKXX) for endoplasmic reticulum sorting of type I membrane proteins in the C-terminus of the Env protein of several FV species. By mutational analysis, we demonstrated that the ERRS was responsible for intracellular recycling of Env of the chimpanzee variant of simian foamy virus, SFV-cpz(hu). To date, ERRSs have not been found in any other retroviral glycoprotein.; Another similarity between FV and HBV is their dependence on Env proteins for budding and release of particles such that, in the absence of Envs, no extracellular particles are formed. For HBV, L and S Envs are required for budding; however, S protein alone is{09}form empty, non-infectious lipoprotein particles called subviral particles (SVPs). Because FVs also depend on Env for budding, we wondered whether expression of FV Env alone would drive the assembly and release of SVPs. Our results indicated that, based on equilibrium density gradient and electron microscopy studies, SFVcpz(hu) Env was capable of forming SVPs. The FV SVPs were morphologically similar in shape and size to FV viral-like particles composed of Gag and Env proteins. These results suggest that, unlike conventional retroviruses, the FV Env, as opposed to the core protein, Gag, is the predominant protein responsible for driving particle budding and release. This unusual property of FV Env further demonstrates 1 similarities that FV shares with HBV.