In the absence of viral envelope gene expression, cells expressing human im
munodeficiency virus type 1 HIV-1) gag and pol, accessory HIV functions, an
d a vector genome RNA produce and secrete large amount of noninfectious vir
us-like particles (VLPs) into the conditioned medium. After partial purific
ation, such HIV-1 VLPs can be made infectious in cell-free conditions in vi
tro by complex formation with lipofection reagents or with the G protein of
vesicular stomatitis virus (VSV-G). The resulting in vitro-modified HIV-1
particles are able to infect nondividing cells. Infectivity of envelope-fre
e HIV VLPs can also be induced by prior modification of target cells throug
h exposure to partially purified VSV-G vesicles. Similarly, infection can b
e carried out by attachment of envelope-free noninfectious VLPs to unmodifi
ed cells followed by subsequent treatment of cells with VSV-G. We interpret
these findings to indicate that interaction between a viral envelope and a
cell surface receptor is not necessary for the initial virus binding to th
e cells but is required for subsequent cell entry and infection.