Blood Coagulation Factor X Exerts Differential Effects on Adenovirus Entry into Human Lymphocytes.

James Findlay,G Blair,Graham Cook

doi:10.3390/v10010020

James Findlay, G Blair + Show 1 more

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https://doi.org/10.3390/v10010020

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Journal: Viruses	Publication Date: Jan 3, 2018
Citations: 5	License type: CC BY 4.0

Affiliation: University of Leeds, St James's University Hospital

Abstract

It has been proposed that blood coagulation factors, principally factor X (FX), enhance the uptake of human adenovirus type 5 (Ad5) into cultured epithelial cells by bridging the viral hexon capsid protein and cell-surface heparan sulphate proteoglycans (HSPGs). We studied the effects of FX on Ad transduction of lymphoid cell lines (NK92MI, a natural killer cell line; Daudi, a B-cell line and Jurkat, a T-cell line) as well as primary peripheral blood lymphocytes (PBL) and HeLa epithelial cells using either replication-deficient Ad5, or a derivative in which the Ad5 fiber was replaced with that of another Ad type, Ad35, termed Ad5F35. PBL and NK92MI were resistant to Ad5 transduction. Transduction of Jurkat and Daudi cells by Ad5 was reduced by FX but without discernible effects on cell-surface Ad5 binding. FX reduced virus binding and transduction of all lymphoid cell lines by Ad5F35, as well as transduction of the T- and Natural Killer (NK)-cell populations of PBL. Flow cytometry analysis showed that all lymphoid cell lines were negative for HSPG components, in contrast to HeLa cells. FX reduced transduction of an HSPG-negative mutant Chinese hamster ovary cell line (CHOpgsA745) by Ad5 and Ad5F35, with Ad5F35 binding also being reduced by FX. These results point to fiber-dependent differences (Ad5 versus Ad35 fiber) in Ad binding to and transduction of human lymphoid and epithelial cells in the presence of FX.

Highlights

Extensive studies in cultured cells in vitro have shown that human adenoviruses (Ads) enter human cells by a two-step process: a primary interaction between the Ad fiber and cell-surface attachment molecules followed by an interaction between the penton base and cell-surface integrins αv β3 and αv β5
The three major cell-surface attachment molecules used by Ads in vitro are the Coxsackie and adenovirus receptor, CAR, CD46 and Desmoglein 2 [1,2,3]
We have investigated the interactions between Ads (Ad5 and Ad5F35), blood coagulation factors and lymphoid cells

Summary

Introduction

Extensive studies in cultured cells in vitro have shown that human adenoviruses (Ads) enter human cells by a two-step process: a primary interaction between the Ad fiber and cell-surface attachment molecules followed by an interaction between the penton base and cell-surface integrins αv β3 and αv β5. The three major cell-surface attachment molecules used by Ads in vitro are the Coxsackie and adenovirus receptor, CAR, (utilized by most Ads including type 5, Ad5), CD46 (a complement inhibitor protein utilized by certain types such as Ad35) and Desmoglein 2. FX binds to hypervariable regions of the major capsid protein, the hexon, and has been proposed to act as a bridge between heparan sulphate proteoglycans (HSPGs) on target cells and hexon trimers in the virus capsid [9,10,11,12,13]. A hybrid Ad, in which the Ad5 fiber was replaced with that of Ad35 (Ad5F35), exhibited reduced liver and increased lung tropism in the presence of FX [15]

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