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Neutralizing monoclonal antibody against a external envelope glycoprotein (gp110) of SIVmac251
S Matsumi1, S Matsushita, K Yoshimura
1Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Abstract:
Three monoclonal antibodies (M318T, M56S and M815) against an external envelope glycoprotein (gp110) of simian immunodeficiency virus (SIV) mac251 were obtained by immunizing BALB/c mice with recombinant gp110 (rgp110). All three monoclonal antibodies reacted with the surface of cells infected with SIVmac251 but not with that of uninfected counterparts. The binding activity of these monoclonal antibodies against native gp110 was confirmed by means of Western blotting. One of them, M318T neutralized SIVmac251 infection both by cell-free and cell-associated viruses. M318T cross-reacted with human immunodeficiency virus type 2 strains (HIV-2 GH1 and ROD isolates) and SIVmac239 isolates. However, the antibody did not cross-neutralize these viral strains. Epitope mapping revealed that the neutralizing epitope recognized by M318T was localized at 8 residues between amino acids 178 and 185 (KRDKTKEY) in gp110, corresponding to the V2 region of human immunodeficiency virus type 1 (HIV-1). Because some antibodies against the V2 region of HIV-1 reportedly neutralize virus infection by interfering with CD4-gp120 interaction, we tested the activity of M318T against the binding of CD4-gp110. However, M318T did not inhibit CD4-gp110 interaction, suggesting the involvement of another unknown mechanism of M318T-mediated neutralization. In analogy with the V2 region of HIV-1, the V2 region of SIV contains a type specific neutralizing epitope recognized by M318T. Although some amino acid sequence in the epitope was conserved for the isolates of SIV and HIV-2 and there was cross-reactivity of the antibody against the strains, neutralization by M318T was associated with a single amino acid (182 T) in the epitope.
Insights
Researchers developed three monoclonal antibodies against simian immunodeficiency virus (SIV) gp110. One antibody, M318T, neutralizes SIV infection and targets a specific epitope in the V2 region, though its mechanism remains unclear.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Monoclonal antibodies are crucial tools for studying viral infections.
- Simian immunodeficiency virus (SIV) is a non-human primate lentivirus closely related to HIV.
- The SIV envelope glycoprotein (gp110) is a key target for neutralizing antibodies.
Purpose of the Study:
- To generate and characterize monoclonal antibodies against SIV gp110.
- To investigate the neutralizing capacity and epitope specificity of these antibodies.
- To elucidate the mechanism of SIV neutralization by a specific antibody.
Main Methods:
- Immunization of BALB/c mice with recombinant gp110 (rgp110).
- Screening of monoclonal antibodies by Western blotting and cell-surface reactivity assays.
- Epitope mapping and neutralization assays against SIV and HIV-2 strains.
- Testing of M318T's effect on CD4-gp110 binding.
Main Results:
- Three monoclonal antibodies (M318T, M56S, M815) were generated against SIV gp110.
- M318T demonstrated potent neutralization of SIVmac251 (cell-free and cell-associated).
- M318T recognized a specific epitope (amino acids 178-185) in the SIV gp110 V2 region, cross-reacting with HIV-2 but not cross-neutralizing.
- M318T did not inhibit CD4-gp110 binding, suggesting a novel neutralization mechanism.
Conclusions:
- M318T is a potent neutralizing antibody against SIV, targeting a V2 region epitope.
- The neutralizing activity of M318T is dependent on a specific amino acid (182 T) within the epitope.
- The mechanism of M318T-mediated SIV neutralization is distinct from CD4-gp120 interaction inhibition.