Abstract
BST2 (CD317, tetherin, HM1.24) is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2) is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N-terminus retained anti-release activity against human immunodeficiency virus type-1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild-type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-κB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-κB.
Highlights
Lentiviruses, which belong to a subfamily of retroviruses, can infect T cells and cause slow disease progression
FBST2 has been characterized with a short Nterminal region and shown to be counteracted by the feline immunodeficiency virus (FIV) envelope glycoprotein [52, 54]
In order to investigate further the potential relevance of the feline BST2 (fBST2) N-terminal region, we studied the impact of its lengthened homolog along the sequence upstream of the annotated methionine on the anti-viral function and other characteristics of this protein
Summary
Lentiviruses, which belong to a subfamily of retroviruses, can infect T cells and cause slow disease progression. Cocka and Bates showed that naturally occurring variants of human BST2 initiating from the internal ATG were partially resistant to Vpu [47] Another recent study showed that the cytoplasmic tail of human BST2 is unnecessary for restricting HIV-1 but important for inducing intracellular signaling, and an N-terminal or internal HA-tagged BST2 was found to cause the loss of functions of anti-virus release and NF-κB activation [56]. Based on these observations, we hypothesized that the shorter N-terminal cytoplasmic region of the fBST2 protein may lack the ability to induce NF-κB activation, and the HA tag can compromise the functions of fBST2. These results provide further insight into the function of human BST2
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