Bioengineering lactic acid bacteria to secrete the HIV-1 virucide cyanovirin.
An urgent need exists to prevent the sexual transmission of HIV-1. With prevalence rates exceeding 35% in parts of sub-Saharan Africa, increasing attention has been placed on developing and testing microbicidal agents capable of preventing virus transmission at mucosal sites. HIV-1 microbicides must meet several requirements before their widespread use. The drugs must be able to neutralize a diversity of HIV-1 strains, not induce mucosal inflammation, be associated with minimal side effects, and be effective for a prolonged period after a single application. Recent work has demonstrated the utility of recombinant lactic acid bacteria (LAB) as agents of mucosal drug delivery. Here, we describe the bioengineering of strains of LAB to secrete the prototypic virucidal compound cyanovirin (CV-N) and demonstrate the anti-HIV-1 activity of secreted CV-N. Our results suggest that recombinant LAB may serve as effective microbicidal compounds and deserve in vivo testing in simian immunodeficiency virus models of mucosal virus transmission.
Pusch
Oliver
O
Center of Anatomy and Cell Biology, Laboratories of Genome Dynamics, Medical University of Vienna, Vienna, Austria.
Boden
Daniel
D
Hannify
Sean
S
Lee
Fred
F
Tucker
Lynne D
LD
Boyd
Michael R
MR
Wells
Jerry M
JM
Ramratnam
Bharat
B
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D005818:Genetic Engineering / Q000379:methods*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D048191:Lactiplantibacillus plantarum / Q000235:genetics* / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000821:virology; D008826:Microbial Sensitivity Tests / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins; C107733:cyanovirin N