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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Analysis of a primary isolate-like virus from simian and human immunodeficiency virus-infected macaque having broad
Yasuyuki Miyazaki1, Takeo Kuwata, Jun Takehisa
1Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Kyoto 606-8507, Japan.
Abstract:
To investigate the changes of neutralizing antibodies and viruses during simian and human immunodeficiency virus (SHIV) infection, we examined the cross-neutralizing ability of sequential sera from three macaques infected with SHIV, NM-3rN, and analyzed the sensitivity of the reisolate to neutralizing antibodies. Neutralizing activities of macaques' sera against the parental HIV-1 showed a persistent increase. Neutralizing activities were highly strain specific, but the spectrum of the neutralizing activity expanded against various clades of primary HIV-1s at 3 years after infection in one of the three macaques. The reisolate from an NM3-rN-infected macaque at 56 wpi, designated as R4356, was neutralized by sera from this macaque at a much lower titer than NM-3rN, even by the sera collected 2 years after the reisolation. Sera from macaques that were newly infected with R4356 also did not neutralize R4356 despite neutralizing NM-3rN strongly. These results suggested that long-term persistent infection with SHIV induced neutralizing antibodies with a broad spectrum. However, a virus resistant to the neutralizing antibodies emerged in the persistently infected macaque.
Insights
Long-term simian-human immunodeficiency virus (SHIV) infection in macaques boosted neutralizing antibodies. However, resistant viral strains emerged, challenging the antibody response during persistent SHIV infection.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Simian-human immunodeficiency virus (SHIV) infection models are crucial for understanding human immunodeficiency virus (HIV) pathogenesis.
- Investigating the interplay between host immune responses and viral evolution during persistent infection is vital for vaccine development.
Purpose of the Study:
- To assess the development of neutralizing antibodies and viral resistance during long-term SHIV infection in macaques.
- To analyze the cross-neutralizing capacity of macaque sera against different HIV-1 clades and viral isolates.
Main Methods:
- Sequential serum samples from three macaques infected with SHIV NM-3rN were collected over time.
- The cross-neutralizing activity of these sera against parental HIV-1 and various primary HIV-1 strains was evaluated.
- The sensitivity of a reisolate (R4356) from a persistently infected macaque to neutralizing antibodies was analyzed.
Main Results:
- Macaque sera showed a persistent increase in neutralizing activity against parental HIV-1.
- Neutralizing activity expanded against diverse HIV-1 clades in one macaque after 3 years.
- A SHIV reisolate (R4356) exhibited significant resistance to neutralization by autologous sera, even from later time points.
Conclusions:
- Persistent SHIV infection can induce broadly neutralizing antibodies in macaques.
- Viral evolution leads to the emergence of strains resistant to the host's neutralizing antibody response.
- Understanding this immune escape mechanism is critical for designing effective HIV therapies and vaccines.
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