3D-Structure of the interior fusion peptide of HGV/GBV-C by 1H NMR, CD and molecular dynamics studies

Mazzini, Stefania; Fernández-Vidal, Mónica; Galbusera, V.; Castro-Roman, Francisco; Bellucci, Maria Cristina; Ragg, Enzio; Haro, Isabel

doi:10.1016/j.abb.2007.05.024

Cited by 5 publications

(3 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, no cellular receptor(s) for GBV-C E2 has been identified yet. The E2 region between the amino acids 279 to 298 is supposed to represent the fusogenic peptide and can adopt helical structure slightly inserted into membranes (16,20). Haro and coworkers (10) could also demonstrate in biophysical assays that the peptide from amino acids 269 to 286 interacts with the fusion peptide of HIV-1 gp41.…”

Section: Gb Virus C (Gbv-c) a Positive-strand Rna Virus Of The Flavimentioning

confidence: 95%

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Koedel

Eissmann

Wend

et al. 2011

J Virol

View full text Add to dashboard Cite

The nonpathogenic human GB virus C (GBV-C), a member of the Flaviviridae, is highly prevalent in individuals with HIV-1 infections or with parenteral and sexual risk factors. Long-term GBV-C viremia has been associated with better survival or improved diagnosis in several epidemiological studies. In a previous study we reported that the E2 glycoprotein of GBV-C interferes with HIV-1 entry in vitro. To address the question what region of the E2 protein is involved in suppression of HIV-1 replication, we performed an E2-derived peptide scanning and determined the HIV-inhibitory activity of each peptide in HIV replication assays. We demonstrate here that peptides representing the N-terminal part of the E2 protein from amino acids (aa) 29 to 72 are able to inhibit efficiently HIV-1 replication in vitro. In particular, the peptides P6-2 (representing the E2-region from aa 45 to 64) and P4762 (aa 37 to 64) showed the highest potency in HIV replication assays performed on TZM-bl cells with 50% inhibitory concentrations between 0.1 and 2 M. However, primary HIV-1 isolates representing clades A to H showed a high variability in their sensitivity to E2 peptides. Pseudovirus inhibition assays revealed that the sensitivity is determined by the gp120/gp41 envelope proteins. Using HIV-1 BlaM-Vpr-based fusion assays, we demonstrate that the E2-derived peptides prevent HIV-1 binding or fusion, presumably via interaction with the HIV-1 particle. Together, these findings reveal a new mechanism of viral interference, suggesting that the envelope protein E2 of GBV-C target directly HIV-1 particles to avoid entry of these virions.

show abstract

Section: Gb Virus C (Gbv-c) a Positive-strand Rna Virus Of The Flavimentioning

confidence: 95%

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Koedel

Eissmann

Wend

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

“…Additional physiochemical analyses with Langmuir phospholipid monolayers demonstrate that the 279–298 peptide modifies the surface behaviour of phospholipid monolayers, further suggesting that this peptide may be involved in membrane fusion [61]. Of note, the 279–298 peptide is unstructured in aqueous solution, but forms an amphipathic helical structure in the presence of lipids and model membranes, further supporting a role in virus-cell fusion [62]. …”

Section: Gb Virus C Envelope Glycoproteinsmentioning

confidence: 99%

GB virus type C interactions with HIV: the role of envelope glycoproteins

Mohr

Stapleton

2009

Journal of Viral Hepatitis

110

180

View full text Add to dashboard Cite

SUMMARY GB virus C/hepatitis G virus (GBV-C/HGV) is the most closely related human virus to hepatitis C virus (HCV). GBV-C is lymphotropic and not associated with any known disease, although it is associated with improved survival in HIV-infected individuals. In peripheral blood mononuclear cells, GBV-C induces the release of soluble ligands for HIV entry receptors (RANTES, MIP-1a, MIP-1b and SDF-1), suggesting that GBV-C may interact with lymphocytes to induce a chemokine and/or cytokine milieu that is inhibitory to HIV infection. Expression of GBV-C envelope glycoprotein E2 in CD4+ T cells or addition of recombinant E2 to CD4 cells recapitulates the HIV inhibition seen with GBV-C infection. Like HCV E2, GBV-C E2 is predicted to be post-translationally processed in the endoplasmic reticulum and is involved with cell binding. The C-termini of GBV-C E1 and E2 proteins contain predicted transmembrane domains sharing features with HCV TM domains. To date, cellular receptor(s) for GBV-C E2 have not been identified. GBV-C E2-mediated HIV inhibition is dose-dependent and HIV replication is blocked at the binding and/or entry step. In addition, a putative GBV-C E2 fusion peptide interferes with HIV gp41 peptide oligomerization required for HIV-1 fusion, further suggesting that GBV-C E2 may inhibit HIV entry. Additional work is needed to identify the GBV-C E2 cellular receptor, characterize GBV-C E2 domains responsible for HIV inhibition, and to examine GBV-C E2-mediated fusion in the context of the entire envelope protein or viral-particles. Understanding the mechanisms of action may identify novel approaches to HIV therapy.

show abstract

“…(279-298) peptide modifies the surface behavior of phospholipid monolayers, suggesting that this peptide interacts with lipids and should be a candidate in future studies of GBV-C fusion peptides (Larios et al, 2006). Of note, the E2(279-298) peptide is unstructured in aqueous solution, but forms an amphipathic helical structure in the presence of model membranes, further supporting a role in virus-cell fusion (Mazzini et al, 2007).…”

Section: Fusion Peptidesmentioning

confidence: 87%

GB virus C

Mohr¹

View full text Add to dashboard Cite

GB virus C (GBV-C) is a nonpathogenic lymphotropic virus that replicates in B and T lymphocytes. Infection with GBV-C is documented worldwide and is common: between 1% and 5% of healthy blood donors are viremic at the time of donation. Antibodies to GBV-C proteins are not usually detected during viremia, and antibodies to the GBV-C envelope glycoprotein E2 develop following the clearance of viremia. Although GBV-C viremia may persist for decades, viremia usually clears within 2 years following infection in the majority of individuals infected by blood transfusion. A chimpanzee variant of GBV-C, designated GBV-C cpz , is found in captive and noncaptive chimpanzees and its prevalence and natural history are uncharacterized. HIV-infected individuals who are co-infected with GBV-C survive longer than those without GBV-C. GBV-C infection of PBMCs inhibits the replication of HIV isolates and one of the mechanisms for this is the downregulation of HIV coreceptors and secretion of the coreceptor ligands. Additional mechanisms of HIV inhibition by GBV-C are examined in this dissertation. The GBV-C envelope glycoprotein E2 contributes directly to the inhibition of HIV infection. Incubation of recombinant E2 with PBMCs at 4°C prior to HIV infection results in a decrease in HIV replication, and only HIV enveloped pseudoparticle transduction, not VSV-G enveloped pseudoparticle transduction, is inhibited by GBV-C E2. This suggests that GBV-C E2 inhibits HIV infection at an entry step when the HIV envelope proteins interact with cellular receptors and membranes. How GBV-C E2 interacts with cellular surfaces and which cellular proteins are utilized for GBV-C binding and entry are unknown. Here, we characterize GBV-C E2 binding to human PBMCs, murine cells, and multiple transformed cell lines to identify the PBMC subset to which E2 binds and to identify candidate cellular receptors involved in GBV-C binding and entry. Understanding how GBV-C E2 interacts with cellular surfaces is critical to determining how it inhibits HIV entry. v ABSTRACT GB virus C (GBV-C) is a nonpathogenic lymphotropic virus that replicates in B and T lymphocytes. Infection with GBV-C is documented worldwide and is common: between 1% and 5% of healthy blood donors are viremic at the time of donation. Antibodies to GBV-C proteins are not usually detected during viremia, and antibodies to the GBV-C envelope glycoprotein E2 develop following the clearance of viremia. Although GBV-C viremia may persist for decades, viremia usually clears within 2 years following infection in the majority of individuals infected by blood transfusion. A chimpanzee variant of GBV-C, designated GBV-C cpz , is found in captive and noncaptive chimpanzees and its prevalence and natural history are uncharacterized. GBV-C research was initially performed by viral hepatitis research groups because it was predicted to cause hepatitis. The realization that GBV-C did not cause hepatitis resulted in a marked reduction in research activity. Because Hepatitis C virus co-infection worsens the cl...

show abstract

3D-Structure of the interior fusion peptide of HGV/GBV-C by 1H NMR, CD and molecular dynamics studies

Cited by 5 publications

References 69 publications

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

GB virus type C interactions with HIV: the role of envelope glycoproteins

GB virus C

Contact Info

Product

Resources

About