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.

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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