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

Janet L. Douglas, Ying Bai, Jean K. Gustin, Ashlee V. Moses

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)182-196
Number of pages15
JournalVirology
Volume441
Issue number2
DOIs
StatePublished - Jul 5 2013

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Keywords

  • BST-2
  • HIV-1
  • Immune evasion
  • Innate immunity
  • Tetherin
  • Viral egress
  • Vpu

ASJC Scopus subject areas

  • Virology

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