title: Activity of HIV entry and fusion inhibitors expressed by the human vaginal colonizing probiotic Lactobacillus reuteri RC-14.
abstract: Novel therapeutic approaches are needed to combat the rapid increase in HIV sexual transmission in women. The probiotic organism Lactobacillus reuteri RC-14 which safely colonizes the human vagina and prevents microbial infections, has been genetically modified to produce anti-HIV proteins which were capable of blocking the three main steps of HIV entry into human peripheral blood mononuclear cells. The HIV entry or fusion inhibitors were fused to the native expression and secretion signals of BspA, Mlp or Sep in L. reuteri RC-14 and the expression cassettes were stably inserted into the chromosome. L. reuteri RC-14 expressed the HIV inhibitors in cell wall-associated and secreted forms. L. reuteri RC-14 expressing CD4D1D2-antibody-like fusion proteins were able to bind single or dual tropic coreceptor-using HIV-1 primary isolates. This is the first study to show that a well-documented and proven human vaginal probiotic strain can express potent functional viral inhibitors, which may potentially lower the sexual transmission of HIV.
authors.affiliation: Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA. liuj@u.washington.edu
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Liu
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
authors.forename: Yonghou
authors.initials: Y
authors.lastname: Jiang
authors.forename: Mark S
authors.initials: MS
authors.lastname: Turner
authors.forename: Che-Chung
authors.initials: CC
authors.lastname: Tsai
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006678:HIV / Q000187:drug effects / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D052197:Limosilactobacillus fermentum / Q000302:isolation & purification; D052200:Limosilactobacillus reuteri / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000382:microbiology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019936:Probiotics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014621:Vagina / Q000382:microbiology*; D053585:Virus Attachment
chemical_list: D001426:Bacterial Proteins; C105995:BspA protein, bacteria; D023581:HIV Fusion Inhibitors; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins