T Cell Surface Glycoproteins in Development and Viral Infections 
genesis analysis to identify the region of CD4 that 
binds to the viral envelope glycoprotein. This in- 
formation, coupled to the recent elucidation of 
CD4's three-dimensional structure, may facilitate 
the development of agents that block binding. 
Although human cells expressing the CD4 mol- 
ecule are susceptible to HIV infection, murine 
cells expressing CD4 bind virus but are resistant 
to infection. This resistance, we have found, is 
due to the inability of the viral envelope to fuse to 
the murine plasma membrane. It is likely that a 
human-specific plasma membrane molecule 
other than CD4 is required for fusion of virus to 
target cells. To identify such a molecule and to 
isolate its gene, we have packaged a selectable 
marker within the HFV particle. Such particles 
bind to CD4-bearing human cells, are internal- 
ized, and are processed to generate a proviral 
DNA that is integrated in the host genome. The 
cells are then grown in selection media. 
These virus particles do not infect CD4-bearing 
murine cells. But if the particles are prepared 
with an envelope glycoprotein that can normally 
interact with murine cells, the selectable HIV ge- 
nome is integrated in the cells. Efforts are under 
way to transfer human genes into the murine cells 
to permit cell survival after infection with the 
selectable virus. It is hoped that identification of 
a second molecule involved in HIV entry may 
lead to the design of novel agents to interfere 
with the virus's spread. 
We have utilized this system to demonstrate 
that the HIV envelope glycoprotein can be re- 
placed by that of the other pathogenic human ret- 
rovirus, human T cell leukemia virus (HTLV), to 
form HIV (HTLV) pseudotypes. HTLV causes T 
cell leukemias and lymphomas and myelopa- 
thies. Individuals infected with both HFV and 
HTLV have more rapid progression of HFV disease 
than those infected with HIV alone. Since both 
viruses infect T lymphocytes, it is likely that 
mixed viral particles can form in vivo. We have 
demonstrated that mixed particles (pseudo- 
types) that form in vitro have an expanded host 
range — i.e., HIV particles, endowed with the 
HTLV-I envelope glycoprotein, can readily infect 
CD4-deficient cells. Thus mixed particles may 
have an important role in HFV pathogenesis, par- 
ticularly in infection of cells that do not have HIV 
receptors, such as cells of the central nervous 
system. 
In addition to investigating HIV infection, we 
are using the hybrid particles to study the yet un- 
characterized HTLV receptor. 
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