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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, Tamaraa,*; Hoffmann, Rebeccab,*; Rohrhofer, Anettea; Audebert, Franzc; Salzberger, Berndd; Korn, Klause; Schuster, Philippf; Eichler, Juttab; Schmidt, Barbaraa,f

doi: 10.1097/QAD.0000000000001926
BASIC SCIENCE: CONCISE COMMUNICATION
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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.

aInstitute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg

bDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg

cGemeinschaftspraxis Alte Mälzerei

dInfectious Diseases, University Hospital of Regensburg, Regensburg

eInstitute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg

fInstitute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.

Correspondence to Barbara Schmidt, MD, Institute of Clinical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Tel: +49 941 944 6404; fax: +49 941 944 6402; e-mail: barbara.schmidt@ukr.de

Received 18 January, 2018

Revised 5 May, 2018

Accepted 14 May, 2018

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Copyright © 2018 Wolters Kluwer Health, Inc.