TY - JOUR
T1 - Characterization of twin-cysteine motif in the V2-loop region of gp120 in primate lentiviruses
AU - Bowder, Dane
AU - Thompson, Jesse
AU - Durst, Kate
AU - Hollingsead, Haley
AU - Hu, Duoyi
AU - Wei, Wenzhong
AU - Xiang, Shi Hua
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Envelope trimer
KW - Gp120
KW - Primate lentiviruses (PLV)
KW - Simian immunodeficiency viruses (HIV)
KW - Simian immunodeficiency viruses (SIV)
KW - Twin-cysteine motif (TCM)
KW - V2-loop
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U2 - 10.1016/j.virol.2018.04.013
DO - 10.1016/j.virol.2018.04.013
M3 - Article
C2 - 29729526
AN - SCOPUS:85046656082
SN - 0042-6822
VL - 519
SP - 180
EP - 189
JO - Virology
JF - Virology
ER -