scholarly journals Naturally Occurring Variability in the Envelope Glycoprotein of HIV-1 and Development of Cell Entry Inhibitors

Biochemistry ◽  
2010 ◽  
Vol 49 (11) ◽  
pp. 2359-2367 ◽  
Author(s):  
Evan T. Brower ◽  
Arne Schön ◽  
Ernesto Freire
Keyword(s):  
Envelope Glycoprotein ◽  
Cell Entry ◽  
Entry Inhibitors ◽  
Naturally Occurring ◽  
Hiv 1

scholarly journals The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

Retrovirology ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. 89 ◽  
Author(s):  
Fiorella Rossi ◽  
Bianca Querido ◽  
Manideepthi Nimmagadda ◽  
Simon Cocklin ◽  
Sonia Navas-Martín ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Entry Inhibitors ◽  
Macrophage Tropism ◽  
Altered Sensitivity ◽  
V3 Region ◽  
Hiv 1

scholarly journals Rapid Dissociation of HIV-1 from Cultured Cells Severely Limits Infectivity Assays, Causes the Inactivation Ascribed to Entry Inhibitors, and Masks the Inherently High Level of Infectivity of Virions

2009 ◽  
Vol 84 (6) ◽  
pp. 3106-3110 ◽  
Author(s):  
Emily J. Platt ◽  
Susan L. Kozak ◽  
James P. Durnin ◽  
Thomas J. Hope ◽  
David Kabat
Keyword(s):  
Immunofluorescence Microscopy ◽  
Cultured Cells ◽  
Cell Entry ◽  
Inhibitory Effects ◽  
Entry Inhibitors ◽  
Ccr5 Antagonists ◽  
High Level ◽  
Hiv 1

ABSTRACT By using immunofluorescence microscopy to observe and analyze freshly made HIV-1 virions adsorbed onto cells, we found that they are inherently highly infectious, rather than predominantly defective as previously suggested. Surprisingly, polycations enhance titers 20- to 30-fold by stabilizing adsorption and preventing a previously undescribed process of rapid dissociation, strongly implying that infectivity assays for many viruses are limited not only by inefficient virus diffusion onto cells but also by a postattachment race between entry and dissociation. This kinetic competition underlies inhibitory effects of CCR5 antagonists and explains why adaptive HIV-1 mutations overcome many cell entry limitations by accelerating entry.

Development and Evaluation of a FACS-Based Medium-Throughput Assay for HCV Entry Inhibitors

2009 ◽  
Vol 14 (6) ◽  
pp. 620-626 ◽  
Author(s):  
Sigrid Ziegler ◽  
Bernd Kronenberger ◽  
Beatrice A.-M. Albrecht ◽  
Artur Kaul ◽  
Anna-Lena Gamer ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Basic Research ◽  
Cell Entry ◽  
Luciferase Reporter ◽  
Human Hepatoma ◽  
Screening System ◽  
Human Hepatoma Cells ◽  
Entry Inhibitors ◽  
Fast Screening ◽  
Key Events

The interaction between the hepatitis C virus (HCV) envelope glycoprotein E2 and the human tetraspanin protein CD81 is one of the key events involved in HCV cell entry. Therefore, compounds that interfere with this interaction may be useful tools for basic research and potential drugs for the treatment of HCV infection. The authors describe a medium-throughput assay for ligands of the E2 binding site on the CD81 receptor. In the assay, human hepatoma cells are incubated with the test compounds and stained with a fluorescently labeled anti-CD81 antibody (JS81). Flow cytometry is used to detect the level of bound antibody, reflecting the inhibitory potencies of the compounds. Eighty percent of compounds active in the assay show efficacy in an infection assay using luciferase reporter genome in cell culture. Thus, the assay can be used as a fast screening system for inhibitors of interaction of viral E2 to host cell CD81-LELs. ( Journal of Biomolecular Screening 2009;620-626)

scholarly journals Evolution of the Envelope Glycoprotein of HIV-1 Clade B toward Higher Infectious Properties over the Course of the Epidemic

2018 ◽  
Vol 93 (6) ◽  
Author(s):  
Mélanie Bouvin-Pley ◽  
Maxime Beretta ◽  
Alain Moreau ◽  
Emmanuelle Roch ◽  
Asma Essat ◽  
...  
Keyword(s):  
Functional Properties ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Viral Fitness ◽  
Cell Entry ◽  
Viral Population ◽  
Target Cells ◽  
Subtype B ◽  
Antigenic Evolution ◽  
Hiv 1

ABSTRACT We showed previously that during the HIV/AIDS epidemic, the envelope glycoprotein (Env) of HIV-1, and in particular, the gp120 subunit, evolved toward an increased resistance to neutralizing antibodies at a population level. Here, we considered whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. We tested the infectivity of a panel of Env-pseudotyped viruses derived from patients infected by subtype B viruses at three periods of the epidemic (1987 to 1991, 1996 to 2000, and 2006 to 2010). Pseudotyped viruses harboring Env from patients infected during the most recent period were approximately 10-fold more infectious in cell culture than those from patients infected at the beginning of the epidemic. This was associated with faster viral entry kinetics: contemporary viruses entered target cells approximately twice as fast as historical viruses. Contemporary viruses were also twice as resistant as historical viruses to the fusion inhibitor enfuvirtide. Resistance to enfuvirtide correlated with a resistance to CCR5 antagonists, suggesting that contemporary viruses expanded their CCR5 usage efficiency. Viruses were equally captured by DC-SIGN, but after binding to DC-SIGN, contemporary viruses infected target cells more efficiently than historical viruses. Thus, we report evidence that the infectious properties of the envelope glycoprotein of HIV-1 increased during the course of the epidemic. It is plausible that these changes affected viral fitness during the transmission process and might have contributed to an increasing virulence of HIV-1. IMPORTANCE Following primary infection by HIV-1, neutralizing antibodies (NAbs) exert selective pressure on the HIV-1 envelope glycoprotein (Env), driving the evolution of the viral population. Previous studies suggested that, as a consequence, Env has evolved at the HIV species level since the start of the epidemic so as to display greater resistance to NAbs. Here, we investigated whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. Our data provide evidence that the infectious properties of the HIV-1 Env increased during the course of the epidemic. These changes may have contributed to increasing virulence of HIV-1 and an optimization of transmission between individuals.

Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC

2012 ◽  
Vol 54 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Leonardo Augusto Luvison Araújo ◽  
Dennis Maletich Junqueira ◽  
Rubia Marília de Medeiros ◽  
Maria Cristina Cotta Matte ◽  
Sabrina Esteves de Matos Almeida
Keyword(s):  
Resistance Mutations ◽  
Entry Inhibitors ◽  
Naturally Occurring ◽  
Hiv 1

scholarly journals Residues in the gp41 Ectodomain Regulate HIV-1 Envelope Glycoprotein Conformational Transitions Induced by gp120-Directed Inhibitors

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Beatriz Pacheco ◽  
Nirmin Alsahafi ◽  
Olfa Debbeche ◽  
Jérémie Prévost ◽  
Shilei Ding ◽  
...  
Keyword(s):  
Amino Acid ◽  
Conformational Changes ◽  
Envelope Glycoprotein ◽  
Coiled Coil ◽  
Bound State ◽  
Heptad Repeat ◽  
Amino Acid Residues ◽  
Entry Inhibitors ◽  
Gp41 Ectodomain ◽  
Hiv 1

ABSTRACT Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the prehairpin intermediate, in which the gp41 heptad repeat 1 (HR1) coiled coil is assembled at the trimer axis. In nature, HIV-1 Envs must balance the requirements to maintain the noncovalent association of gp120 with gp41 and to evade the host antibody response with the need to respond to CD4 binding. Here we show that the gp41 HR1 region contributes to gp120 association with the unliganded Env trimer. Changes in particular amino acid residues in the gp41 HR1 region decreased the efficiency with which Env moved from the unliganded state. Thus, these gp41 changes decreased the sensitivity of HIV-1 to cold inactivation and ligands that require Env conformational changes to bind efficiently. Conversely, these gp41 changes increased HIV-1 sensitivity to small-molecule entry inhibitors that block Env conformational changes induced by CD4. Changes in particular gp41 HR1 amino acid residues can apparently affect the relative stability of the unliganded state and CD4-induced conformations. Thus, the gp41 HR1 region contributes to the association with gp120 and regulates Env transitions from the unliganded state to downstream conformations. IMPORTANCE The development of an efficient vaccine able to prevent HIV infection is a worldwide priority. Knowledge of the envelope glycoprotein structure and the conformational changes that occur after receptor engagement will help researchers to develop an immunogen able to elicit antibodies that block HIV-1 transmission. Here we identify residues in the HIV-1 transmembrane envelope glycoprotein that stabilize the unliganded state by modulating the transitions from the unliganded state to the CD4-bound state.

scholarly journals The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM).

1994 ◽  
Vol 269 (16) ◽  
pp. 12240-12247 ◽  
Author(s):  
E. Decroly ◽  
M. Vandenbranden ◽  
J.M. Ruysschaert ◽  
J. Cogniaux ◽  
G.S. Jacob ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Design, Synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors

2021 ◽  
pp. 116000
Author(s):  
Francesca Curreli ◽  
Shahad Ahmed ◽  
Sofia M. Benedict Victor ◽  
Ildar R. Iusupov ◽  
Evgeny A. Spiridonov ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Small Molecule ◽  
Design Synthesis ◽  
Entry Inhibitors ◽  
Hiv 1
Sign in / Sign up

Export Citation Format

Share Document