Human recombinant myeloperoxidase antiviral activity on cytomegalovirus

Abstract

In vitro incubation of human cytomegalovirus (Towne strain) with 8 U/ml human recombinant myeloperoxidase plus sodium chloride and glucose nearly abolished viral infectivity. To assay the effect on intracellular infection, cell toxicity of the enzymes was first studied. Even the high dose of 16 U/ml of recombinant myeloperoxidase plus 10 mU/ml glucose oxidase did not decrease MRC5 cell growth. By contrast, this dose reduced proliferation of activated THP1 cells. Even half of the myeloperoxidase dose proved slightly toxic to these cells. Non-cytotoxic concentrations of the reagents were used to monitor their effect on cytomegalovirus infection. In MRC5 cells, even the low dose of 4 U/ml myeloperoxidase plus glucose oxidase inhibited synthesis of cytomegalovirus early antigens, as tested by immunofluorescence. Viral release in the supernatant was decreased by 4 logs. In THP1 cells, which produce endogenously hydrogen peroxide, myeloperoxidase alone (8 U/ml) decreased the formation of early and late antigens by 53 and 44%, respectively.

Role of epithelial nitric oxide in airway viral infection

“…NO and ROS, particularly O 2 − , rapidly form the reactive nitrogen oxide, peroxynitrite (ONOO − ), that may cause oxidation and nitration of amino acid residues of proteins or guanine of DNA, lipid peroxidation, and DNA cleavage, all of which can cause cellular dysfunction and injury leading to cell death [91,93,95]. Myeloperoxidase (MPO), eosinophil peroxidase (EPO), and lactoperoxidase (LPO) are members of the mammalian peroxidase superfamily and play specific and complementary roles in host defense through oxidative pathways [90,92,[95][96][97][98][99]. MPO is highly expressed in neutrophils, monocytes, and certain subpopulations of tissue macrophages [100], and LPO is present in human airway epithelium [101].…”

“…Virus-infected cells produce peroxide that drives the virucidal peroxidase-H 2 O 2 -halide system to catalyze the H 2 O 2 -dependent peroxidation of halides and pseudohalides to produce antimicrobial hypohalous acids. Hypochlorous acids (HOCl) play an important role in killing microorganisms including virus but also injure normal tissues [90,[96][97][98][99]. Recent studies show that members of the mammalian peroxidase superfamily can reduce NO levels [101][102][103][104][105].…”

Impact of Human Cytomegalovirus Latent Infection on Myeloid Progenitor Cell Gene Expression

“…MPO has been shown to inactivate influenza virus (70) and human immunodeficiency virus type 1 (22). It has also been shown to almost completely abolish infectivity of CMV in HFFs and significantly reduce the formation of both early and late CMV antigens in a monocyte cell line (THP-1) rendered permissive to productive infection by differentiation with the phorbol ester tetradecanoyl phorbol acetate (12). The mechanism of action of MPO against CMV is unknown, but this enzyme disrupts influenza virus envelope proteins (70).…”

Expression and characterization of bovine lactoperoxidase by recombinant vaccinia virus

“…Myeloperoxidase has been shown to inactivate influenza virus (Yamamoto et al 1991) and HIV-1 virus (Klebanoff and Kazazi 1995). Human recombinant MPO has been shown to have a virucidal effect on HIV-1 virus (Moguilevsky et al 1992;Chochola et al 1994) and cytomegalovirus (El Messaoudi et al 2002). However, few studies have examined whether LPO inhibits virus infection in vitro and in vivo.…”