HIV entry inhibition by the envelope 2 glycoprotein of GB virus C

Abstract

Epidemiological studies have revealed an association between GB virus C (GBV-C) long-term viraemia and ameliorated HIV disease progression. We have provided evidence that a single protein of GBV-C, the glycoprotein E2, interferes with early HIV replication steps of both X4- and R5-tropic HIV strains. Preincubation with anti-E2 antibody specifically abrogates the inhibitory effect. Results were confirmed by the in-vitro expression of GBV-C E1/E2 encoding RNA.

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

“…Not surprisingly, the effect mediated by E2 peptides is not fully identical in quantitative and qualitative concerns to the HIVinhibitory effect induced by the recombinant truncated E2 protein (E2 340 Fc) used in earlier studies. Recombinant E2 protein is approximately 2 orders of magnitude more potent compared to P4-7 or P6-2, it is effective toward R5-tropic HIV-1 reporter viruses pseudotyped with the ADA envelope, and preincubation of cells is sufficient to induce the HIV-inhibitory effect, while with E2-derived peptides only preincubation with virus led to HIV-1 inhibition (13). Despite the fact that recombinant E2 protein and E2-derived peptides both interfere with early HIV-1 entry events, 20mer peptides derived from the N terminus of the E2 protein apparently do not mediate the full "E2 …”

“…Xiang et al demonstrated that expression of NS5A induces the expression of SDF-1 and the downregulation of CXCR4 (35,38). Previously, we demonstrated that the GBV-C envelope glycoprotein E2 is involved in HIV-1 inhibition (13). Incubation of PBMC with recombinant truncated E2 protein of GBV-C, where the hydrophobic transmembrane anchor was exchanged by the human IgG1 Fc fragment, led to significant replication suppression of clinical HIV-1 isolates and HIV-1 reporter particles pseudotyped with X4-and R5-tropic HIV-1 envelope proteins.…”

“…In order to perform an E2 peptide scanning to identify the region(s) responsible for E2-mediated HIV-1 inhibition, 20mer peptides overlapping in 10 amino acids (aa) were synthesized, representing the truncated soluble version of the GBV-C E2 protein (according to GenBank accession number AF121950) from aa 1 to 340 used in earlier studies (13) (Fig. 1).…”

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección

“…Con base en estos resultados, y con el fin de determinar el mecanismo de inhibición, se han diseñado pseudopartículas de VIH (con la glicoproteína del VSG) capaces de ingresar a la célula mediante endocitosis, encontrando ausencia de inhibición, lo que sugiere que E2 interviene específicamente en el paso de adhesión del VIH 42,43 . Otros estudios más recientes sugieren la posibilidad de que péptidos derivados de la glicoproteína E2 del GBV-C tendrían la capacidad de inhibir la unión al receptor y/o la fusión de VIH vía interacción con la partícula viral, o incluso realizar la inhibición en pasos tempranos pos-entrada 43,44 (Figura 3B); Koedel y cols., utilizaron 32 péptidos sintéticos derivados de E2, que al ser adicionados a cultivos celulares antes de la infección con VIH (pseudopartículas virales), inhibieron el paso de entrada.…”

Behaviour of a peptide sequence from the GB virus C/hepatitis G virus E2 protein in Langmuir monolayers: Its interaction with phospholipid membrane models

“…It has been described in the literature that one of these proteins, the GBV-C/HGV E2 protein, regulates the entrance of HIV into the cell [18]. The two structural envelope glycoproteins, E1 and E2 of GBV-C/HGV, are located within the amine-terminus of the polyprotein, while the nonstructural proteins reside within the carboxy-terminal part ( Fig.…”