Polyadenylic-polyuridylic acid referred to as poly(A).poly(U), is a sy
nthetic double-stranded RNA that has been shown to manifest both antit
umoral and immunodulatory activities. Previously, we have reported tha
t poly(A).poly(U) inhibits HIV infection in cell cultures. Here we pro
vide direct evidence to demonstrate that the inhibitory action of poly
(A).poly(U) is through its capacity to prevent entry of HIV particles
into CD4-positive T lymphocytes. Such inhibition of HPV entry is also
observed in the case of other polyanions such as heparin, dextran sulf
ate, and poly(I).poly(C). The mechanism of inhibition appears to occur
postbinding of HIV particles to the CD4 receptor molecules, because t
he binding of the external envelope glycoprotein of HIV-1 (gp120) is n
ot affected significantly in the presence of poly(A).poly(U) or other
polyanions. These results confirm the potential of poly(A).poly(U) as
an antiviral drug against HIV infection.