Abstract
Membrane proteins of enveloped viruses have been reported to undergo palmitoylation, a post-translational modification often having a critical role in the function of these viral proteins and hence viral replication. In this study, we report that the foamy virus (FV) envelope (Env) glycoprotein is palmitoylated. Specifically, we found that bovine foamy virus (BFV) Env (BEnv) is palmitoylated at amino acid positions C58 and C59 by BDHHC3 and BDHHC20 in a DHHC motif-dependent manner. In addition, mutations C58S and C58/59S significantly decrease cell surface expression of BEnv, subviral particle (SVP) egress, and its membrane fusion activity, thus ultimately inhibiting BFV replication. The C59S mutation exerts a minor effect in this regard. Taken together, these data demonstrate that the function of BEnv in the context of BFV replication is under the regulation of palmitoylation.
Highlights
Palmitoylation of the Bovine FoamyFoamy viruses (FVs, termed spumaviruses) constitute the only genus of the Spumaretrovirinae subfamily in the Retroviridae family for their unique replication strategy [1,2]
The results showed that the az-Rho fluorescent signal was visualized only in the protein sample that was metabolically labeled with alk-16 but not in the control with dimethyl sulfoxide (DMSO), indicating that BEnv is modified by palmitoylation (Figure 1A)
We report that palmitoylation of BEnv regulates BEnv targeting to the cell surface, is indispensable for the membrane fusion activity of BEnv and its budding and incorporation into subviral particle (SVP), and warrants efficient replication of bovine foamy virus (BFV)
Summary
Palmitoylation of the Bovine FoamyFoamy viruses (FVs, termed spumaviruses) constitute the only genus of the Spumaretrovirinae subfamily in the Retroviridae family for their unique replication strategy [1,2]. FVs are nonpathogenic retroviruses that cause endemic infection in non-human primates, felines, equines, and bovines [3]. They can be transmitted to humans through zoonotic infection [4,5,6]. BFV is detectable in the general human food chain through beef and raw milk, which poses a potential risk of zoonotic transmission of BFV to humans [8] Owning to their non-pathogenic nature and broad tissue tropism, FVs have been engineered as safe viral vectors for gene transfer as well as gene therapy [9,10]
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