Abstract
Human BCA2/RNF115/Rabring7 (hBCA2) is a RING type E3 ubiquitin ligase with the ability of autoubiquitination or promoting protein ubiquitination. It also acts as a host restriction factor has BST2-dependent and BST2-independent antiviral activity to inhibit the release of HIV-1. In a previous study, we demonstrated that feline BCA2 (fBCA2) also has E3 ubiquitin ligase activity, although its antiviral mechanism remained unclear. In this study, we showed that fBCA2 can interact with feline BST2 (fBST2) and exhibits an fBST2-independent antiviral function, and the RING domain is necessary for the antiviral activity of fBCA2. fBCA2 could degrade HIV-1 Gag and restrict HIV-1 transcription to counteract HIV-1 but not promote the degradation of HIV-1 through lysosomal. Furthermore, for both fBCA2 and hBCA2, restricting viral transcription is the main anti-FIV mechanism compared to degradation of FIV Gag or promoting viral degradation. Consequently, transcriptional regulation of HIV or FIV by BCA2 should be the primary restriction mechanism, even though the degradation mechanism is different when BCA2 counteracts HIV or FIV. This may be due to BCA2 has a special preference in antiviral mechanism in the transmission of primate or non-primate retroviruses.
Highlights
Lentiviruses, which are a genus within the Orthoretrovirinae subfamily that belongs to the Retroviridae family, can infect T cells and cause slow disease progression
In order to verify whether feline BCA2 (fBCA2) could interacts with feline BST2 (fBST2), we performed an immunoprecipitation assay with HEK293T cells transfected with Human BCA2/RNF115/Rabring7 (hBCA2)-Flag, fBCA2Flag, and either human BST2 (hBST2)-HA or fBST2-HA
The results showed that fBCA2 could interact with fBST2, fBST2 has a short cytoplasmic tail, which is similar to the interaction of hBCA2 with hBST2 (Figure 1A)
Summary
Lentiviruses, which are a genus within the Orthoretrovirinae subfamily that belongs to the Retroviridae family, can infect T cells and cause slow disease progression. The domestic cat lineage can be infected by retroviruses such as feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), and feline foamy virus (FFV). FIV enters T cells via CXCR4 and CD134 and exhibits similarities with HIV-1 in its genomic structure, propagation mechanism, infection process, and pathogenicity (Tomonaga et al, 1992; Willett et al, 1997a,b; Poeschla and Looney, 1998; Shimojima et al, 2004). Domestic cats are considered as relevant natural animal models for studying acquired immunodeficiency syndrome (AIDS) in humans, as well as the development of potential therapeutic strategies for immune control leading to non-progression (Lehman et al, 2010; Yamamoto et al, 2010; Poeschla, 2011)
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