The Synthetic Immunomodulator Murabutide Controls Human Immunodeficiency Virus Type 1 Replication at Multiple Levels in Macrophages and Dendritic Cells

Selective Regulation of Human Immunodeficiency Virus-Infected CD4+Lymphocytes by a Synthetic Immunomodulator Leads to Potent Virus Suppression In Vitro and in hu-PBL-SCID Mice

“…Total cellular RNA was extracted using RNAzol (Bioprobe Systems, Montreuil, France) and was amplified using rTth Polymerase (Perkin-Elmer, Norwalk, Conn.) in the presence of the GAG06-GAG04 primer pair to detect the HIV-1 unspliced Gag-Pol mRNA and the BSS-KPNA primer pair to detect the singly spliced mRNA, as described elsewhere (2,17,41,57). To measure proviral DNA levels, total cellular DNA was extracted and subjected to 20 or 40 repeated rounds of amplification with Amplitaq Gold DNA polymerase (Perkin-Elmer).…”

“…PCR amplification of ␤-globin or ␤-actin sequences was performed to standardize for cell equivalence. HIV-1 proviral DNA in each sample was measured by using the GAG06-GAG04 primer pair (17,46). All PCR products were separated on acrylamide gels and visualized by ethidium bromide staining.…”

“…Today, limited success has been achieved and the link between immunological effects and clinical benefit has yet to be demonstrated. In an effort to identify clinically acceptable immunomodulators with potential application in the immunotherapy of HIV disease, we have previously evaluated the capacity of Murabutide, a safe synthetic muramyl dipeptide (MDP) derivative, to activate APCs and to suppress viral replication (17). Independent of its ability to induce HIV-suppressive ␤-chemokines and in the absence of a direct effect on viral enzymes, this immunomodulator was found to regulate cellular pathways in macrophages and in dendritic cells, leading to potent inhibition of proviral DNA integration and of virus transcription.…”

SS-56, a novel cellular target of autoantibody responses in Sjögren syndrome and systemic lupus erythematosus

“…Recently, this immunomodulator was also found capable of regulating CD4 + lymphocytes from HIV-1 patients, leading to potent suppression of viral replication in vitro (25). These effects were revealed to target the nuclear transport of viral preintegration complexes and virus transcription through the regulation, at least partly, of cellular genes necessary for different steps in the virus life cycle (24)(25)(26). To better define the HIV-suppressive activity of Murabutide, we carried out a differential display analysis on CD8-depleted PBMCs, stimulated or not with Murabutide, from one HIV-1 patient.…”

“…with a capacity to suppress HIV-1 replication in antigenpresenting cells (24). Recently, this immunomodulator was also found capable of regulating CD4 + lymphocytes from HIV-1 patients, leading to potent suppression of viral replication in vitro (25).…”