1742-4690-3-S1-S100.fm BioMed Central Page 1 of 1 (page number not for citation purposes) Retrovirology Open AccessOral presentation Natural and engineered antibodies against HIV Edward A Berger* Address: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA * Corresponding author The humoral arm of the immune system exerts continual selective pressure on HIV replication in the infected per- son. We have described a conserved epitope within the gp120 V3 loop that is masked in the native Env trimer on CCR5-restricted (R5) HIV-1 virions, but fully exposed on CXCR4-using (X4, R5X4) virions. The ability of a mono- clonal antibody against this epitope to selectively neutral- ize CXCR4-using but not CCR5-restricted primary isolates raises the question of whether in vivo neutralizing anti- body selection pressure in the acutely infected person plays a major role in the selective transmission of R5 viruses. We are exploiting antibodies to engineer novel bifunc- tional proteins against HIV infection. One agent, desig- nated sCD4-17b, is based on the sequential receptor binding mechanism of gp120: first to CD4, then to core- ceptor. The sCD4 moiety of the chimeric protein binds and induces the conformational change required to expose/create the highly conserved "bridging sheet" involved in coreceptor binding and containing the 17b epitope. The potent neutralizing activity of sCD4-17b against diverse HIV-1 primary isolates suggests its poten- tial utility as a topical microbicide to protect against HIV- 1 sexual transmission. [1,2]. References 1. Lusso P, Earl PL, Sironi F, Santoro F, Ripamonti C, Scarlatti G, Longhi R, Berger EA, Burastero SE: Cryptic nature of a conserved, CD4- inducible V3 loop neutralization epitope in the native enve- lope glycoprotein oligomer of CCR5-restricted, but not CXCR4-using, primary human immunodeficiency virus type 1 strains. J Virol 2005, 79:6957-6968.