Characterization of twin-cysteine motif in the V2-loop region of gp120 in primate lentiviruses

Dane Bowder, Jesse Thompson, Kate Durst, Haley Hollingsead, Duoyi Hu, Wenzhong Wei, Shi Hua Xiang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The twin-cysteine motif (TCM) in the V2 loop region of gp120, identified in our previous report on the simian immunodeficiency virus mac239 (SIVmac239), is a conserved evolutionary element in all primate lentiviruses except for HIV-1 which has lost the TCM during cross-species transmission. In this study, we have further explored the TCM in other SIV and HIV-2 strains. Our data shows that strains from different evolutionary lineages have different phenotypes when the twin-cysteines are removed. In the SIVsm/HIV-2 lineage, removal of the twin-cysteines decreases envelope trimer stability, but in the SIVagm lineage, a blockage of gp160 processing is observed. Molecular modeling has confirmed that the twin-cysteines do form a disulfide bond in the gp120 subunit, which interacts with the V1 loop to stabilize the envelope trimer. Therefore, we hypothesize that if the TCM is added back to HIV-1, it will enhance envelope stability for vaccine immunogen design.

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalVirology
Volume519
DOIs
StatePublished - Jun 2018

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Keywords

  • Envelope trimer
  • Gp120
  • Primate lentiviruses (PLV)
  • Simian immunodeficiency viruses (HIV)
  • Simian immunodeficiency viruses (SIV)
  • Twin-cysteine motif (TCM)
  • V2-loop

ASJC Scopus subject areas

  • Virology

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