Blocking HIV-1 infection by chromosomal integrative expression of human CD4 on the surface of Lactobacillus helveticus R0052.

Lactobacillus bacteria are potential delivery vehicles for biopharmaceutical molecules because they are well-recognized as safe microorganisms that naturally inhabit the human body. The goal of this study is to employ these lactobacilli to combat human immunodeficiency virus (HIV-1) infection and transmission. By using a chromosomal integration method, we engineered the Lactobacillus helveticus R0052 strain to display human CD4, the HIV-1 receptor, on the cell surface. Since human CD4 can bind to any infectious HIV-1 particles, the engineered lactobacilli can potentially capture HIV-1 of different sub-types and prevent infection. Our data demonstrate that the CD4-carrying bacteria are able to adsorb HIV-1 particles and reduce infection significantly in vitro , and also block intrarectal HIV-1 infection in a humanized mouse model in preliminary tests in vivo Our results support the potential of this approach to decrease the efficiency of HIV-1 sexual transmission. IMPORTANCE In the absence of an effective vaccine, alternative approaches to block HIV-1 infection and transmission with commensal bacteria expressing antiviral proteins are being considered. This report provides a proof-of-concept by using Lactobacillus stably expressing the HIV-1 receptor, CD4, to capture and neutralize HIV-1 in vitro and in a humanized mouse model. The stable expression of antiviral proteins like CD4 following genomic integration of the corresponding genes into this Lactobacillus strain may contribute to the prevention of HIV-1 sexual transmission.