Glycosylation and oligomeric state of envelope protein might influence HIV-1 virion capture by α4β7 integrin

The alpha 4137 integrin present on host cells recognizes the V1V2 domain of the HIV-1 envelope protein. This interaction might be involved in virus transmission. Administration of alpha 4 beta 7-specific antibodies inhibit acquisition of SIV in a macaque challenge model. But the molecular details of V1V2: alpha 4 beta 7 interaction are unknown and its importance in HIV-1 infection remains controversial. Our biochemical and mutational analyses show that glycosylation is a key modulator of V1V2 conformation and binding to alpha 4 beta 7. Partially glycosylated, but not full; glycosylated, envelope proteins are preferred substrates for alpha 4 beta 7 binding. Surprisingly, monomers of the envelope protein bound strongly to alpha 4 beta 7 whereas trimers bound poorly. Our results suggest that a conformationally flexible V1V2 domain allows binding of the HIV-1 virion to the alpha 4 beta 7 integrin, which might impart selectivity for the poorly glycosylated HIV-1 envelope containing monomers to be more efficiently captured by alpha 4 beta 7 integrin present on mucosal cells at the time of HIV-1 transmission.