Disease relevance of SPCS3

• SPC3, a synthetic peptide derived from the V3 domain of human immunodeficiency virus type 1 (HIV-1) gp120, inhibits HIV-1 entry into CD4+ and CD4- cells by two distinct mechanisms [1].
• In agreement with this hypothesis, SPC3 treatment after HIV-1 exposure dramatically reduced the number of infected cells without altering gp120-CD4 interaction or viral gene expression [1].
• V3 loop-derived peptide SPC3 inhibits infection of CD4- and galactosylceramide- cells by LAV-2/B [2].

High impact information on SPCS3

• In the present study, we investigated the mechanisms of action of SPC3 in these cell types--i.e., CD4+ lymphocytes and CD4- epithelial cells expressing galactosylceramide (GalCer), an alternative receptor for HIV-1 gp120 [1].
• Recently, we reported that a synthetic multibranched peptide (SPC3) containing eight V3-loop consensus motifs (GPGRAF) inhibited HIV-1 infection in both CD4+ and CD4- susceptible cells [1].
• Accordingly, SPC3 was found to inhibit the binding of gp120 to the GalCer receptor [1].
• In contrast, SPC3 blocked HIV-1 entry into CD4-/GalCer+ human colon epithelial cells when present in competition with HIV-1 but had no effect when added after infection [1].
• Liposome-associated SPC3 were tested for both inhibition of cell-cell fusion and infection with HIV-1 clones [3].

Chemical compound and disease context of SPCS3

• Thus, the data suggest that SPC3 affects HIV-1 infection by two distinct mechanisms: (i) prevention of GalCer-mediated HIV-1 attachment to the surface of CD4-/GalCer+ cells and (ii) post-binding inhibition of HIV-1 entry into CD4+ lymphocytes [1].

Biological context of SPCS3

• As assessed using antibodies, the conformation of the receptor binding site and of V3 presented on membrane Env was not affected by the presence of SPC3 during biosynthesis [4].
• The antiviral property of SPC3 was further investigated for its ability to inhibit LAV-2/B, an HIV-2 clone with a CD4-independent tropism [2].
• A multibranched peptide construct (SPC3) derived from the conserved sequence of the third variable domain (V3) of the human immunodeficiency virus (HIV) envelope (Env) inhibits HIV infectivity [4].
• SPC3 is a peptide construct (eight branches of the GPGRAF motif) derived from the consensus sequence present at the apex of the third variable domain of the human immunodeficiency virus (HIV) envelope (Env) [5].

Anatomical context of SPCS3

• These data suggested that SPC3 did not inhibit the binding of HIV-1 to CD4+ lymphocytes but interfered with a post-binding step necessary for virus entry [1].
• SPC3 was found to interact with CD4+ cell membrane with a K0.5 value in the range of 500 nM [5].
• Syncytium formation was impaired when human CD4+ cells expressed recombinant HIV Env in the presence of SPC3 [4].
• SPC3 inhibited the LAV-2/B-mediated infection of B-cell line which does not express the CD4 and the galactosylceramide molecules on their cell surface, suggesting an SPC3-sensitive CD4/galactosylceramide-independent pathway of viral infection in HIV susceptible cells [2].
• Budding of secretory granules causes the lumen to acidify to <pH 6.0, which is both necessary and sufficient to trigger SPC3-mediated proteolytic conversion of proopiomelanocortin to ACTH [6].

Associations of SPCS3 with chemical compounds

• These data suggest that the liposome approach may be used to improve SPC3 antiviral efficacy [3].
• Moreover, only some of these anti-HIV active analogs inhibited the binding of [3H]suramin (a polysulfonyl compound which displays a high affinity for the V3 loop) to SPC3, a synthetic peptide which contains the conserved GPGRAF region of the V3 loop [7].
• SPC3 was entrapped in various liposomal formulations, either different in size (mean diameter of 100 and 250 nm), SPC3 concentration or cholesterol content [3].

Analytical, diagnostic and therapeutic context of SPCS3

• Changes in mRNA from the SpC3 gene (Sp064) were also followed by RT-PCR [8].
• Properties of HIV envelope expressed in the presence of SPC3, an Env-derived peptide drug under phase II clinical trials [4].

References