Distribution and three-dimensional structure of AIDS virus envelope spikes

Abstract

Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had approximately 14 and approximately 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.

Efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed gp41-derived peptides

“…Primate immunodeficiency viruses share the same envelope protein structure, 26,27 including the N-and C-terminal hydrophobic a-helixes 28 that form a six-helix bundle during virus fusion with the cell membrane. Despite limited deduced amino-acid sequence homology among different primate immunodeficiency viruses (Table 2B), the principle a-helical structures are preserved.…”

Polymeric Anti‐HIV Therapeutics

“…Viral matrix protein (p17) is located in a viral lipid bilayer membrane that also displays the envelope spike glycoproteins gp120 and gp41 on the exterior of the virus. [8,10] In addition, accessory proteins Nef, Vif and Vpr are also packaged in the virion. The gp41 trimer is anchored to the virus via a transmembrane domain and the gp120 trimer is closely associated to the gp41 trimer via van der Waals interactions as well as hydrogen bonds.…”

“…The gp41 trimer is anchored to the virus via a transmembrane domain and the gp120 trimer is closely associated to the gp41 trimer via van der Waals interactions as well as hydrogen bonds. [8,10] Despite having a crucial role in virus-cell membrane fusion, the gp41 trimer is initially embedded by the gp120 trimer and is only exposed after virus-cell interactions commence. Each gp41 strand of the trimer consists of two heptad repeat regions, HR1 and HR2 located at the N-terminus and Cterminus, respectively, separated by a loop.…”

Targeting the protein–protein interactions of the HIV lifecycle

“…These include reverse transcriptase, integrase, protease, as well as p6, Vif, Vpr and Nef. associate into homotrimers 6 that mediate binding and entry to target cells. The primary receptor for HIV is the glycoprotein CD4, which is expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages and dendritic cells.…”