Lineage-specific differences in the gp120 Inner Domain Layer 3 of Human and Simian Immunodeficiency Viruses

Authors

• Shilei Ding, Centre de Recherche du CHUM
• Halima Medjahed, Centre de Recherche du CHUM
• Jérémie Prévost, Centre de Recherche du CHUM
• Mathieu Coutu, Centre de Recherche du CHUM
• Shi-Hua Xiang, University of Nebraska-LincolnFollow
• Andrés Finzi, Centre de Recherche du CHUMFollow

Document Type

Article

Date of this Version

2016

Citation

J. Virol. doi:10.1128/JVI.01215-16

Comments

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Abstract

Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved Tryptophan 375 (Trp 375) in HIV-2/SIVsmm. Here we investigated the role of SIV Layer 3 on viral entry, cell-to-cell fusion and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 Layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity which directly contacts CD4. In summary, our results suggest that SIV Layer 3 has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in Layer 3 from HIV-1 and SIV.