Induction and antiviral activity of human β-defensin 3 in intestinal cells with picornavirus infection

Abstract

Antimicrobial peptides produced by epithelial and immune cells protect tissues from various infections. Whether enterovirus infection leads to stimulation of antimicrobial peptide expression is unknown. We examined antimicrobial peptide mRNA and protein production in HT-29 colon adenocarcinoma cells infected with picornaviruses. The antiviral activity of increased antimicrobial peptide production was evaluated by using a recombinant peptide and corresponding gene overexpression. Enterovirus infection enhanced both the mRNA expression and secretion of human β-defensin (hBD) 3 in intestinal epithelial cells but did not increase expression of human neutrophil peptide 1-3 (HNP 1-3), HNP4, human defensin 5 (HD5), HD6, hBD1, hBD2, and hBD5. The recombinant but not the intracellularly overexpressed hBD3 inhibited enterovirus (EV) 71, coxsackievirus A16 (CVA16), CVB5 and poliovirus 1 (PV1) infecting HT-29 cells. Our results suggest that enterovirus infection induces hBD3 production in human intestinal epithelial cells and that hBD3 can exert extracellular anti-enterovirus activity.

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

“…Finally, addition of recombinant hBD-3 to colon adenocarcinoma HT-29 cells inhibited EV-71, CV-A16, CV-B5, and poliovirus 1 infection. However, enterovirus replication was not impaired in genetically modified HT-29 cells overexpressing hBD-3 intracellularly, suggesting extracellular antiviral activity of the peptide (Chen et al, 2018). Regarding other viral species, hBD-1 and, more markedly, hBD-2 neutralized infectivity of the Phil82 strain of IAV (Doss et al, 2009).…”

“…Similarly, IAV/H1N1 as well as RSV infections induced a huge increase in hBD-2 secretion whereas HCoV-OC43 did not (Kota et al, 2008;Boda et al, 2018). In intestinal epithelial cells, enterovirus (EV) infection enhanced the secretion of hBD-3 but not that of αand other β-defensins (Chen et al, 2018). In fresh peripheral blood mononuclear cells, the other major source of hBD production in human, only hBD-1 coding mRNAs were detected in non-stimulated cells among the four known hBDs (Oppenheim et al, 2003).…”

“…In the context of skin infections, antiviral properties of hBDs have been demonstrated against HSV, VZV, and VACV, similarly to LL-37, but also against EV-71 and Coxsackievirus (CV) A16, the main etiological agents of hand, foot and mouth disease (Hazrati et al, 2006;Howell et al, 2004;Crack et al, 2012;Chen et al, 2018). hBD-3, and in a lesser extent hBD-1, exerted anti-HSV-2 activities whereas hBD-2 did not but diminished VZV replication in HaCat cells, a keratinocyte cell line (Hazrati et al, 2006;Scudiero et al, 2010).…”

Antiviral peptides against Enterovirus A71 causing hand, foot and mouth disease

“…Similarly, natural antimicrobial peptides produced by the normal flora of human gut lining such as human β-defensin 3 (hBD3) was found to be up-regulated during picornavirus infections, indicating a natural extracellular antiviral response. It was reported that poliovirus-1, CV-A16 and CV-B5 infections were inhibited significantly by hBD3 in vitro [ 44 ]. This is consistent with earlier reports of mouse β-defensin 3 that was identified to protect HeLa cells in vitro and myocarditis in mice from CV-B3 infection [ 45 ].…”

“…Only recombinant hBD3 proteins but not intracellularly expressed hBD3 in colon adenocarcinoma intestinal cells (HT-29 cells) were able to confer inhibitory effects, confirming that inhibitory effects were extracellularly mediated. This suggested that hBD3 had the ability to block the entry of EV-A71 into the host cells during the early phase of infection to provide protection from infection [ 44 ].…”