کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6141013 | 1227192 | 2013 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A comparative mutational analysis of HIV-1 Vpu subtypes B and C for the identification of determinants required to counteract BST-2/Tetherin and enhance viral egress A comparative mutational analysis of HIV-1 Vpu subtypes B and C for the identification of determinants required to counteract BST-2/Tetherin and enhance viral egress](/preview/png/6141013.png)
- HIV subtype B and C Vpu chimeras confirm that the Vpu TM domain is critical for BST-2 interaction.
- In the context of a destabilized TM domain the elongated Vpu C NH2-terminus prevents BST-2 binding.
- Viral egress determinants in the Vpu B COOH-terminus are missing or non-functional in Vpu C.
We have undertaken a genetic strategy to map Vpu regions necessary for BST-2 antagonism and viral egress. This approach is based on our identification of an egress-defective Vpu variant encoded by an HIV-1 subtype C strain. We constructed a series of chimeric Vpu molecules made from the Vpu C variant and Vpu B from a standard laboratory strain. The TM domain from the inactive Vpu C, which contains multiple non-conserved residues, was responsible for a significant decrease in egress activity and BST-2 downregulation, confirming the functional importance of the Vpu TM domain. However, for complete inactivation, both the N-terminus and TM domain from the inactive Vpu C molecule were required, suggesting a new role for the Vpu N-terminus. In addition, determinants in the C-terminus of Vpu B that may be involved in efficient TGN accumulation were also necessary for enhanced viral egress but are missing or non-functional in Vpu C.
Journal: Virology - Volume 441, Issue 2, 5 July 2013, Pages 182-196