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Antibody recognition of SIVmac envelope peptides in plasma from macaques experimentally infected with SIV/Mne
A Shafferman1, A Layne, J Sadoff
1Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, D.C. 20307.
Abstract:
Four stretches of amino acid sequences encoded in conserved HIV-1 env domains and four parallel regions of the SIVmac env (two from gp120 and two from gp41/p32E) were fused to the NH2 terminus of beta-galactosidase by recombinant DNA techniques and used to analyze sera from three macaque species experimentally infected with SIV/Mne. All SIVmac env sequences were recognized by sera from the SIV/Mne-inoculated macaques. Western blot analysis performed with whole SIV/Mne, SIVmac, SIVagm, and HIV-1 antigens and sera from SIV/Mne-infected macaques also demonstrates that SIV/Mne is immunologically more closely related to SIVmac than to SIVagm or to HIV-1. Antibody levels to the gp120 NH2-terminal SIV-88 epitope appear to decrease in the infected Macaca nemestrina with progression of disease, as was also reported for the parallel HIV-1 epitope in HIV-1-infected individuals. Sera from all infected macaques reacted with the p32E-SIV-582 epitope (EKYLEDQAQLNAWGCAFRQVC). High titers to this immunodominant epitope could be detected at least 9 weeks postinfection and at a time when primarily the p28 and p32E antibodies were detectable in Western blots performed with whole disrupted SIV/Mne virus. In the majority of animals, antibody titers of 1:100,000 to SIV-582 develop during the infection and persist until death. Antibody responses to the SIV env epitopes in SIV/Mne-infected macaques thus resemble in many aspects (prevalence and immunogenicity) those observed previously for the corresponding HIV-1 env epitopes in HIV-1-infected humans.
Insights
This study analyzed simian immunodeficiency virus (SIV) env sequences in macaques, finding SIV/Mne is immunologically closer to SIVmac than other viruses. Antibody responses to specific SIV env epitopes mirrored those seen in human immunodeficiency virus (HIV) infections.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) are lentiviruses with related envelope (env) proteins.
- Understanding cross-species immune responses is crucial for developing effective vaccines and therapies.
Purpose of the Study:
- To investigate the immunological relatedness of SIV/Mne to SIVmac, SIVagm, and HIV-1 using env gene sequences.
- To characterize antibody responses to specific SIV env epitopes in experimentally infected macaques.
Main Methods:
- Recombinant DNA techniques were used to fuse conserved HIV-1 and SIVmac env sequences to beta-galactosidase.
- Sera from SIV/Mne-infected macaques were analyzed using Western blot assays against various viral antigens and recombinant env fragments.
Main Results:
- SIV/Mne demonstrated closer immunological relationship to SIVmac compared to SIVagm and HIV-1.
- All infected macaques recognized SIVmac env sequences, with high antibody titers to the immunodominant p32E-SIV-582 epitope.
- Antibody levels to a gp120 NH2-terminal epitope decreased with disease progression, similar to HIV-1 infections.
Conclusions:
- SIV/Mne shares significant immunological features with SIVmac.
- Antibody responses to SIV env epitopes in macaques resemble those observed in human HIV-1 infections, providing insights into lentiviral immunopathogenesis.