Immunoglobulin-Like Domain of HIV-1 Envelope Glycoprotein gp120 Encodes Putative Internal Image of Some Common Human Proteins

Abstract

By examining sequence similarity between the V3-loop of gp120 from various HIV-1 isolates and human proteins, we found that the V3 loop portion KKGIAIGPGR in strain New York 5 (HIV-1NY5) shares 70% identical residues with the collagen-like region (CLR) of human complement component C1q-A. C1q CLR was found to react with autoantibodies from several autoimmune disorders. Thus, we assumed that it would be of interest to find out the C1q reactivity with antibodies from AIDS sera. The results obtained show that the V3 loop-derived synthetic peptide KKGIAIGPGRTLY reacts both with AIDS patients sera and with antibodies purified on the V3 loop peptide-affinity column. The same affinity-purified antibodies bind also to C1q molecules. Since, according to our previous results, HIV-1 V3 loops and immunoglobulin heavy chain variable regions (Ig VH) share several common features, we suggest that the envelope of HIV-1NY5 bears a functional internal image of the C1q-A CLR epitope. Therefore, gp120 could manipulate the immune network and contribute to HIV-induced autoimmunity.

C1q Autoantibodies in HIV Infection: Correlation to Elevated Levels of Autoantibodies against 60-kDa Heat-Shock Proteins

“…Stoiber et al (12) also demonstrated that antibodies isolated on a C1q-affinity column from HIV patient's sera reacted not only with C1q but also with HIV-1 gp120. Similar results were reported by Metlas et al (13). Therefore it can be assumed that due to the homologies between the two proteins (12), anti-gp120 reacted with solid phase C1q in our system.…”

“…Based on these results, Stoiber et al (12) postulated the possibility of development of C1qAb in HIV infection and found nine sera from HIV-infected subjects to agglutinate erythrocytes coated with antibody and C1q (EAC1q). Metlas et al (13) found a sequence similarity between V3 loop of gp120 of an HIV-1 isolate and collagen-like region of C1q, and also raised the possibility of formation of C1qAb in AIDS. They found antibodies from sera of AIDS patients purified on a V3 affinity column to bind C1q molecules as well.…”

Human Immunodeficiency Virus V3 Peptide-Reactive Antibodies Are Present in Normal HIV-Negative Sera

“…These peptides originate from two common human proteins, C1q and col- lagen type VI, and were identified by sequence alignment procedures as peptides possessing 6-to 7-residue identifies with V3 peptide in a 10-residue stretch. 22 The present results are in apparent discordance with results reported earlier by our group 2 7 ; no reactivity had been detected using sera from healthy subjects and a low but reproducible response was obtained against a collagenous consensus peptide in the sera of HIV-positive subjects. It seems likely that the discrepancy relates in part to the slightly different sequence of the control peptides used in the present study and in part to the methodology followed to couple the peptides to BSA: in the present study glutaraldehyde instead of EDC was used.…”

Template-based recognition of protein fold within the midnight and twilight zones of protein sequence similarity

“…It has been shown (Metlas et al, 1991(Metlas et al, , 1994(Metlas et al, , 1995 that the v3 loop of gp120 and the immunoglobulin variable region exhibit similar DNA and protein sequences. The research group has also shown that the v3 loop of gp120 displays highly significant local similarities to T-cell receptors (Metlas et al, 1995).…”

“…The research group has also shown that the v3 loop of gp120 displays highly significant local similarities to T-cell receptors (Metlas et al, 1995). Metlas et al have postulated that the v3 loop of gp120 is critical in the infectivity of HIV 1 (Metlas et al, 1991(Metlas et al, , 1994(Metlas et al, , 1995.…”