envelope glycoprotein
Structure and AssemblyBiological Characterization of Conserved Residues within the Cytoplasmic Tail of the Pichinde Arenaviral Glycoprotein Subunit 2 (GP2)Several arenaviruses, such as Lassa virus (LASV), can cause severe and lethal hemorrhagic fever diseases with high mortality and morbidity, for which no FDA-approved vaccines or therapeutics are available. Viral entry is mediated by the arenavirus GP complex, which consists of the stable signal peptide (SSP), the receptor-binding subunit GP1, and the transmembrane subunit GP2. The cytoplasmic tail (CT) of GP2 is highly conserved among...
Virus-Cell InteractionsThe Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 AssociationAlthough extensive studies of the transmembrane unit (gp41) of HIV-1 Env have led to a fusion inhibitor clinically used to block viral entry, the functions of different domains of gp41 in HIV-1 fusion and infectivity are not fully elucidated. The polar region (PR) of gp41 has been proposed to participate in HIV-1 membrane fusion in biochemical analyses, but its role in viral entry and infectivity remain unclear. In our effort to...
Pathogenesis and ImmunityPositive Selection at Key Residues in the HIV Envelope Distinguishes Broad and Strain-Specific Plasma Neutralizing AntibodiesMillions of people are still being infected with HIV decades after the first recognition of the virus. Currently, no vaccine is able to elicit bNAbs that will prevent infection by global HIV strains. Several studies have implicated HIV Env diversity in the development of breadth. However, Env evolution in individuals who fail to develop breadth despite mounting potent strain-specific neutralizing responses has not been well defined....
Vaccines and Antiviral AgentsA Coreceptor-Mimetic Peptide Enhances the Potency of V3-Glycan AntibodiesHIV-1 requires both the cellular receptor CD4 and a tyrosine-sulfated coreceptor to infect its target cells. CD4-Ig is a fusion of the HIV-1-binding domains of CD4 with an antibody Fc domain. Previous studies have demonstrated that the potency of CD4-Ig is markedly increased by appending a coreceptor-mimetic sulfopeptide to its C terminus. We investigated whether this coreceptor-mimetic peptide improves the potency of broadly...
Structure and AssemblyConformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble TrimersHIV-1 envelope glycoprotein spikes mediate the entry of the virus into host cells and are a major target for vaccine-induced antibodies. Soluble forms of the envelope glycoproteins that are stable and easily produced have been characterized extensively and are being considered as vaccines. Here, we present evidence that these stabilized soluble envelope glycoproteins differ in multiple respects from the natural HIV-1 envelope...
- Virus-Cell InteractionsHIV-1 gp41 Residues Modulate CD4-Induced Conformational Changes in the Envelope Glycoprotein and Evolution of a Relaxed Conformation of gp120
Binding of the HIV envelope glycoprotein (Env) to cellular CD4 and chemokine receptors triggers conformational changes in Env that mediate virus entry, but premature triggering of Env conformational changes leads to virus inactivation. Currently, we have a limited understanding of the network of residues that regulate Env conformational changes. Here, we identify residues in HR1 of gp41 that modulate conformational changes in response...