A recombinant lactobacillus strain expressing genes coding for restriction enzymes cleaving the HIV genomes for use as a live microbicide strategy against heterosexual transmission of HIV

Abstract

Using genetically engineered endogenous lactobacillus strains colonizing the vagina mucosa to express heterogenous proteins has of late joined the novel strategies aimed at developing a microbicides against HIV. Using the lactobacillus metabolic genome pathway, we found that these bacteria do not naturally produce restriction enzymes, but rather, have a number of putative alien genes of the type. In view of the antiviral defence role of restriction modification systems (RMS), we searched for enzymes that cleave HIV-1, 2 and other SIV genomes using theoretical computational methods. With over 200 such enzymes identified, we present herein a plasmid vector mediated strategy for modifying lactobacillus strains to express RMS islands as an approach to developing a live HIV microbicide. This model is transferable to other viral infections that find their way into humans through mucosal orifices.