Inhibition of HIV-1 infection by human pegivirus type 1-derived peptides is affected by human pegivirus type 1 genotype and HIV-1 coreceptor tropism

Ruegamer, Tamara and Hoffmann, Rebecca and Rohrhofer, Anette and Audebert, Franz and Salzberger, Bernd and Korn, Klaus and Schuster, Philipp and Eichler, Jutta and Schmidt, Barbara (2018) Inhibition of HIV-1 infection by human pegivirus type 1-derived peptides is affected by human pegivirus type 1 genotype and HIV-1 coreceptor tropism. AIDS, 32 (14). pp. 1951-1957. ISSN 0269-9370, 1473-5571

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Abstract

Objective(s): Up to 40% of HIV-1 infected individuals are coinfected with human pegivirus type 1 (HPgV-1). The majority of studies, but not all, have reported a beneficial effect of HPgV-1 coinfection on HIV-1 disease progression. So far, the impact of different HPgV-1 genotypes on different HIV-1 subtypes remains unclear. Methods: Peptides derived from HPgV-1 envelope protein E2, and representing different viral genotypes, were synthesized using Fmoc/t-Bu-based solid phase peptide synthesis. The inhibitory effect of these peptides on the infection of reporter cell lines was tested using an HIV-1 subtype panel representing clades A (n = 2), AG (n = 2), B (n = 6), C (n = 2), D (n = 2), F (n = 2), G (n = 1), G/H (n = 1), and group O (n = 2). Results: HIV-1 infection was blocked more efficiently by peptides derived from HPgV-1 GT2 than GT1 (P = 0.05). The HIV-1 subtype did not affect the degree of inhibition by a peptide derived from HPgV-1 GT2. All CXCR4-/dual-tropic isolates (n = 12), but only half (four out of eight) CCR5-tropic viruses were inhibited by this peptide (P = 0.014). Conclusion: Our data indicate that the inhibitory effect of peptides derived from HPgV-1 E2 protein is dependent on the genotype, suggesting that coinfection with HPgV-1 GT1 is less likely to confer a beneficial effect on HIV-1 disease progression than GT2. The preferential suppression of more pathogenic CXCR4-tropic HIV-1 by peptides derived from HPgV-1 GT2 may explain the favorable effect in patients harboring these HIV-1 isolates. Consequently, HPgV-1 genotype and HIV-1 coreceptor tropism are likely determinants for the beneficial effect of HPgV-1 co-infection in HIV-1-infected individuals. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: GB-VIRUS-C; C/HEPATITIS G VIRUS; HEPATITIS-G VIRUS; DISEASE PROGRESSION; NO INFLUENCE; CLADE-C; COINFECTION; ENTRY; ASSOCIATION; SURVIVAL; CCR5 coreceptors; CXCR4; GBV-C virus; hepatitis G virus; human immunodeficiency virus type 1; human pegivirus type 1; peptides
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 13 Dec 2019 08:31
Last Modified: 13 Dec 2019 08:31
URI: https://pred.uni-regensburg.de/id/eprint/13867

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