Disease relevance of GPGRAF

• All sera obtained after boosting contained HIV-1 binding/fusion-inhibition antibodies, and a significant portion of their activity was blocked by the V3 loop peptide, a result consistent with the presence of antibodies against the region of the V3 loop that participates in fusion [1].
• Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen [2].
• An NMR approach for structure determination of short peptides displayed on the surface of filamentous bacteriophage virions is demonstrated using the hexapeptide GPGRAF that constitutes the principal neutralizing determinant of HIV-1 [3].
• V3 loop peptide sequences from several HIV-1 strains were covalently linked to purified protein derivative (PPD) of Mycobacterium tuberculosis [4].
• We have previously shown that a V3-loop peptide from HIV-1 envelope conjugated to heat-inactivated Brucella abortus (Ba) (V3-Ba) is capable of inducing antibodies that neutralize HIV-1 and cytotoxic T cells (CTL) that kill HIV-1-infected targets, even in mice that lack CD4(+) T cells [5].

High impact information on GPGRAF

• Using a YBF30 V3 loop peptide enzyme immunoassay, we screened 700 HIV-1-positive sera collected in Cameroon; three reacted strongly with the YBF30 peptides and one was confirmed as being related to YBF30 by genetic analysis of a pol fragment [6].
• Sera from two rabbits immunized with a peptide containing only the GPGRAF residues neutralized divergent isolates, including IIIB and MN [7].
• 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 [8].
• We also demonstrate that [3H]suramin binds to multibranched synthetic GPGRAF peptides that block HIV-1 infection in HT-29 cells [9].
• Construction of an HIV-1 peptide vaccine containing a multideterminant helper peptide linked to a V3 loop peptide 18 inducing strong neutralizing antibody responses in mice of multiple MHC haplotypes after two immunizations [10].

Chemical compound and disease context of GPGRAF

• The results showed a 100% sensitivity and specificity for V3 loop peptide and 98% sensitivity and specificity for gp41 peptide containing CGG moiety while the plain peptides showed similar sensitivities but low specificity's, i.e. 98% for V3 loop peptide and 42% for gp41 peptide when reacted with HIV-1 positive sera [11].

Biological context of GPGRAF

• Characterization of these sera revealed that the cross-neutralizing antibodies bound the amino acid sequence GlyProGlyArgAlaPhe (GPGRAF) that is present in both isolates [7].
• This "universal" T cell epitope, which was recognized in donors of many different HLA-DR and -DQ haplotypes, was then used to construct a chimeric peptide containing 19-33 and the third V region loop structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune response to the V3 loop peptide [12].
• A structure-activity relationship study using V3 SPC analogs showed that the most efficient inhibitor of cell fusion was an eight-branched SPC with the hexapeptide motif GPGRAF (i.e., [GPGRAF]8-SPC) [13].
• N-terminal acetylation or incorporation of D-amino acids in the GPGRAF sequence of this SPC resulted in significant loss of activity [13].
• In the present study, we have characterized the cellular binding sites for the V3 peptide SPC3, which possesses eight V3 consensus motifs GPGRAF radially branched on a neutral polyLys core matrix [14].

Anatomical context of GPGRAF

• More importantly, syncytium formation by three different primary clinical HIV isolates was inhibited by the V3 loop peptide from HIV-1 IIIB at a concentration of 1 micrograms/ml [15].
• SPC3 inhibits HIV-1 infection in human lymphocytes and macrophages, while the monomer counterpart of SPC3, i.e., the GPGRAF peptide, has no effect [16].
• Molecular analysis of presentation by HLA-A2.1 of a promiscuously binding V3 loop peptide from the HIV-envelope protein to human cytotoxic T lymphocytes [17].
• Vaccination with rgp160 induced lymphocyte proliferative responses to rgp160, but not to V3 loop peptide [18].
• The MalE hybrid protein (MalE133-V3 loop) was stably expressed in the periplasm of Escherichia coli K12, and the V3 loop peptide was detectable on the surface of the native protein by an anti-gp160 monoclonal antibody (mAb 110-A) [19].

Associations of GPGRAF with other chemical compounds

• In this study mass spectrometry (MS) combined with both liquid (LC) and gas chromatography (GC) has been employed to identify the products formed following ONOO- treatment of three peptides at physiological pH: leucine-enkephalin (YGGFL), V3 loop (GPGRAF), and LVV-hemorphin7 (LVVYPWTQRF) [20].

Gene context of GPGRAF

• In inhibition enzyme-linked immunosorbent assay, the mucin-antibody chimeric peptide could inhibit 71 to 84% of binding to a V3 loop peptide by monoclonal antibodies known to be specific for GPGR in the V3 loop [21].
• In this study we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 of 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF2 to B. abortus [gp120(SF2)-B. abortus] [22].
• In addition to being highly strain specific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV-1(DH12), nor did it block the interaction of gp120 with the CD4 receptor [23].
• These antibodies in sera could bind to both neutralizing epitopes on gp41 peptide, V3 loop peptide and recombinant soluble gp41 (aa539-684) in ELISA assay (antisera dilution: 1:1,600-25,600), while normal sera did not [24].
• Following immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, control proteins, and phytohaemagglutinin [18].

Analytical, diagnostic and therapeutic context of GPGRAF

• However, none of the sera cross-neutralizing ANT70 and IIIB were reactive in ELISA with the ANT70 V3 loop peptide [25].
• OBJECTIVE: To compare the performance of V3-loop peptide enzyme immunoassay (PEIA) methodologies from four different laboratories for subtyping HIV-1, and to determine the causes for the lack of correlation between V3-loop PEIA serotyping and subtyping by sequencing [26].
• Only the sera reactive to the ANT-70 V3 loop peptide from Cameroon and Gabon were confirmed on a specific HIVANT-70 Western blot (i.e., presence of antibodies to the envelope protein gp 120) [27].
• Peripheral blood mononuclear cells (PBMCs) from these people were analyzed by a restriction fragment-length polymorphism (RFLP) assay that involves a sequential endonuclease digestion of a 297-base pair polymerase chain reaction (PCR) fragment; plasma samples were tested by a V3-loop peptide enzyme immunoassay (PEIA) [28].
• Expression of the inserted epitopes in flagellin and their exposure at the surface of flagellar filaments were shown by immunoblotting and immunogold labeling with anti-flagellin (Salmonella d) and anti-HIV-1(IIIB) V3 loop peptide sera [29].

References