An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry.

Abstract:

:Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays. We further investigated the effect of LUMS1 on the activation of T helper (Th) and B cells through flow cytometry. LUMS1 showed binding to (1-2)mannobiose, the minimum glycan epitope of MVN, potently inhibited HIV-1 and HCV with EC50 of 37.2 and 45.3 nM, respectively, and showed negligible cytotoxicity with CC50 > 10 µM against PBMCs, Huh-7.5 and HepG2 cells, and 4.9 µM against TZM-bl cells. LUMS1 did not activate Th cells, and its stimulatory effect on B cells was markedly less as compared to MVN. Together, with these effects, LUMS1 represents a potential candidate for the development of antiviral therapies.

journal_name

Viruses

journal_title

Viruses

authors

Shahid M,Qadir A,Yang J,Ahmad I,Zahid H,Mirza S,Windisch MP,Shahzad-Ul-Hussan S

doi

10.3390/v12020199

subject

Has Abstract

pub_date

2020-02-11 00:00:00

issue

2

issn

1999-4915

pii

v12020199

journal_volume

12

pub_type

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