Potent Inhibition of Replication of Primary HIV Type 1 Isolates in Peripheral Blood Lymphocytes by Negatively Charged Human Serum Albumins

Abstract

We previously reported the antiviral capacity of human serum albumin (HSA), which was modified by the introduction of a single (Suc-HSA) or two carboxylic groups (Aco-HSA) per lysine residue, yielding strongly negatively charged polypeptides. Here we report the antiviral effect of these modified HSAs on replication of primary HIV-1 isolates that differed with respect to syncytium-inducing (SI) capacity and cell tropism. Both Suc-HSA and Aco-HSA potently inhibited replication of primary HIV-1 variants, independent of the SI capacity of the HIV-1 variant, with IC₅₀ values in the range of 50 to 187 μg/ml The inhibition of the formation of syncytia and the absence of proviral DNA products in cells inoculated with HIV-1 in the presence of SucHSA or Aco-HSA pointed to interference at an early level in the virus replication cycle. The inhibitory capacity of Suc-HSA and Aco-HSA on primary HIV-1 variants suggests that these agents are potential candidates for use in antiviral therapy in HIV-infected individuals.