Soybean-derived Bowman-Birk inhibitor (BBI) blocks HIV entry into macrophages

Abstract

Bowman-Birk inhibitor (BBI) is a soybean-derived protease inhibitor that has anti-inflammation and anti-HIV effect. Here, we further investigated the anti-HIV action of BBI in macrophages, focusing on its effect on viral entry. We found that BBI could significantly block HIV entry into macrophages. Investigation of the mechanism (s) of the BBI action on HIV inhibition showed that BBI down-regulated the expression of CD4 receptor (as much as 80%) and induced the production of the CC chemokines (up to 60 folds at protein level) in macrophages. This inhibitory effect of BBI on HIV entry could be blocked by the neutralization antibodies to CC chemokines. These findings indicate that BBI may have therapeutic potential as a viral entry inhibitor for the prevention and treatment of HIV infection.

Bowman‒Birk Inhibitor Suppresses Herpes Simplex Virus Type 2 Infection of Human Cervical Epithelial Cells

“…In addition, BBI could upregulate the expression of tight junction proteins and block HSV-2 infection-mediated reduction of the ZO-1 protein. These observations, in conjunction with our early studies [ 25 , 26 ], indicate that BBI may have therapeutic potential as a natural and cost-effective agent for the prevention and treatment of HSV-2 and other STIs. However, future in vivo studies with suitable animal models are needed in order to validate these in vitro findings and determine the protective effect of BBI on HSV-2 sexual infection.…”

“…BBI has been reported to possess anti-tumor [ 19 , 20 ], anti-inflammation [ 21 , 22 , 23 ], and antiviral activities [ 24 ]. We recently documented that BBI has the ability to induce intracellular antiviral factors that inhibit HIV-1 replication in human macrophages [ 25 , 26 ]. Because HSV-2 infection is a cofactor promoting HIV-1 sexual transmission, we examined whether BBI has an inhibitory effect on HSV-2 infection of human cervical epithelial cells.…”

A fungal effector and a rice NLR protein have antagonistic effects on a Bowman–Birk trypsin inhibitor

“…For example, a soya bean BBI can suppress MMP‐2 and MMP‐9 enzyme activity to inhibit the growth of the two adenocarcinoma cells AGS and HT29 (Fereidunian et al ., 2014). And the soya bean BBI can block HIV entry into macrophages (Ma et al ., 2018). BBI homologs were also identified as antimicrobial proteins in wheat, maize and rice (Chen et al ., 1999; Chilosi et al ., 2000; Qu et al ., 2003).…”

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

“…Reports regarding antimicrobial activities of BBIs are scarce. However, BBI is proved to display antiviral activity toward bovine herpes virus-1 [211], herpes simplex virus type 2 (HSV-2) [212], and HIV [213,214]. Interestingly, HSV-2 infection is considered to facilitate HIV-1 sexual transmission.…”