Background: Human immunodeficiency virus type1 (HIV-1) is the causativ
e agent of AIDS and the subject of intense study. The immature HIV-1 p
article is traditionally described as having a well ordered, icosahedr
al structure made up of uncleaved Gag protein surrounded by a lipid bi
layer containing envelope proteins. Expression of the Gag protein in e
ukaryotic cells leads to the budding of membranous virus-like particle
s (VLPs). Results: We have used cryo-electron microscopy of VLPs from
insect cells and lightly fixed, immature HIV-1 particles from human ly
mphocytes to determine their organization. Both types of particle were
heterogeneous in size, varying in diameter from 1200-2600 Angstrom. L
arger particles appeared to be broken into semispherical sectors, each
having a radius of curvature of approximately 750 Angstrom. No eviden
ce of icosahedral symmetry was found, but local order was evidenced by
small arrays of Gag protein that formed facets within the curved sect
ors. A consistent 270 Angstrom radial density was seen, which included
a 70 Angstrom wide low density feature corresponding to the carboxy-t
erminal portion of the membrane attached matrix protein and the amino-
terminal portion of the capsid protein. Conclusions: Immature HIV-1 pa
rticles and VLPs both have a multi-sector structure characterized, not
by an icosahedral organization, but by local order in which the struc
tures of the matrix and capsid regions of Gag change upon cleavage. We
propose a model in which lateral interactions between Gag protein mol
ecules yields arrays that are organized into sectors for budding by RN
A. (C) Current Biology Ltd ISSN 0960-9822.