Year-end Sale % OFF 
Abstract
BackgroundHTLV-1 Gag protein is a matrix protein that contains the PTAP and PPPY sequences as L-domain motifs and which can be released from mammalian cells in the form of virus-like particles (VLPs). The cellular factors Tsg101 and Nedd4.1 interact with PTAP and PPPY, respectively, within the HTLV-1 Gag polyprotein. Tsg101 forms a complex with Vps28 and Vps37 (ESCRT-I complex) and plays an important role in the class E Vps pathway, which mediates protein sorting and invagination of vesicles into multivesicular bodies. Nedd4.1 is an E3 ubiquitin ligase that binds to the PPPY motif through its WW motif, but its function is still unknown. In the present study, to investigate the mechanism of HTLV-1 budding in detail, we analyzed HTLV-1 budding using dominant negative (DN) forms of the class E proteins.ResultsHere, we report that DN forms of Vps4A, Vps4B, and AIP1 inhibit HTLV-1 budding.ConclusionThese findings suggest that HTLV-1 budding utilizes the MVB pathway and that these class E proteins may be targets for prevention of mother-to-infant vertical transmission of the virus.
Highlights
HTLV-1 Gag protein is a matrix protein that contains the PTAP and PPPY sequences as L-domain motifs and which can be released from mammalian cells in the form of virus-like particles (VLPs)
These results indicate that endogenous Vps4A and Vps4B are sufficient for producing VLPs, but the enzymatic activities of Vps4A and Vps4B are clearly required for efficient budding of HTLV-1
Our results showed that the dominant negative (DN) forms of Vps4A, Vps4B, and AIP1 markedly suppressed VLP production, suggesting that HTLV-1 budding utilizes the multivesicular bodies (MVBs) pathway and that these class E proteins may be the targets for prevention of mother-to-infant vertical transmission
Summary
The Gag polyprotein of HTLV-1 is the only viral protein that is both necessary for and sufficient to drive the release of virus particles through a budding process [1,2,3,4,5,6,7]. To examine the involvement of Vps4A and Vps4B in the egress of HTLV-1 Gag-induced VLP, we analyzed the effects of overexpression of DN mutants of Vps4A and Vps4B, termed Vps4AEQ and Vps4BEQ, respectively (Fig. 1A) [12]. Both DN mutants were expressed as proteins containing a Flag tag at their N-termini. Our results showed that the DN forms of Vps4A, Vps4B, and AIP1 markedly suppressed VLP production, suggesting that HTLV-1 budding utilizes the MVB pathway and that these class E proteins may be the targets for prevention of mother-to-infant vertical transmission
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
