A conformational switch controlling HIV-1 morphogenesis

Assembly df infectious human immunodeficiency virus type 1 (HIV-1) proceeds in two steps. Initially, an immature virus with a spherical capsid shell c onsisting of uncleaved Gag polyproteins is formed. Extracellular proteolyti c maturation causes rearrangement of the inner virion structure, leading to the conical capsid of the infectious virus. Using an in vitro assembly sys tem, we show that the same HIV-1 Gag-derived protein can form spherical par ticles, virtually indistinguishable from immature HIV-1 capsids, as well as tubular or conical Particles, resembling the mature core. The assembly phe notype could be correlated with differential binding of the protein to mono clonal antibodies recognizing epitopes in the HIV-1 capsid protein (CA), su ggesting distinct conformations of this domain. Only tubular and conical pa rticles were observed when the protein lacked spacer peptide SP1 at the C-t erminus of CA, indicating that SP1 may act as a molecular switch, whose pre sence determines spherical capsid formation, while its cleavage leads to ma turation.