Rapid systemic spread and minimal immune responses following SIVsab intrarectal transmission in African green monkeys

Kevin D Raehtz1, Cuiling Xu1,2, Claire Deleage3

  • 1Department of Pathology and.

JCI Insight
|December 6, 2024
PubMed

Insights

Early simian-immunodeficiency virus (SIV) infection in African green monkeys (AGMs) shows rapid viral replication and dissemination. This rapid spread offers no intervention window, highlighting swift pathogenesis in non-natural hosts.

Area of Science:

  • Virology
  • Immunology
  • Primate Models of Infection

Background:

  • African green monkeys (AGMs) are natural hosts of simian-immunodeficiency virus (SIV) and do not develop AIDS.
  • Understanding early SIV infection events is crucial for comprehending pathogenesis in non-natural hosts.

Purpose of the Study:

  • To investigate early SIV infection patterns in intrarectally inoculated AGMs.
  • To understand viral establishment, dissemination, and disease progression dynamics.

Main Methods:

  • 29 adult male AGMs were intrarectally inoculated with SIVsab92018 (SIVsab).
  • Serial sacrifice throughout acute and early chronic infection phases.
  • Ultrasensitive assays used to detect viral replication and viremia.

Main Results:

  • Viral replication foci detected at inoculation site and draining lymphatics by 1-3 days post-infection (dpi).
  • Rapid onset of viremia observed between 2-4 dpi.
  • Systemic viral spread to all surveyed tissues; multiple transmitted/founder viruses identified, indicating a moderate mucosal genetic bottleneck.
  • Resident CD4+ T cells were the initial target cells; no significant alteration in other immune cell populations at the entry site.

Conclusions:

  • Intrarectal SIVsab infection in AGMs is characterized by swift viral dissemination.
  • Lack of major target cell recruitment and no intervention window during the earliest infection stages.
  • Findings are similar to intrarectal transmission but differ from vaginal transmission in macaques.

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