Exposure to SIV in utero results in reduced viral loads and altered responsiveness to postnatal challenge

  • Baker C
  • Swainson L
  • Lin D
 et al. 
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Abstract

HIV disease progression appears to be driven by increased immune activation. Given observations that fetal exposure to infectious pathogens in utero can result in reduced immune responses, or tolerance, to those pathogens postnatally, we hypothesized that fetal exposure to HIV may render the fetus tolerant to the virus, thus reducing damage caused by immune activation during infection later in life. To test this hypothesis, fetal rhesus macaques (Macaca mulatta) were injected with the attenuated virus SIVmac1A11 in utero and challenged with pathogenic SIVmac239 1 year after birth. SIVmac1A11-injected animals had significantly reduced plasma RNA viral loads (P < 0.02) up to 35 weeks after infection. Generalized estimating equations analysis was performed to identify immunologic and clinical measurements associated with plasma RNA viral load. A positive association with plasma RNA viral load was observed with the proportion of CD8(+) T cells expressing the transcription factor, FoxP3, and the proportion of CD4(+) T cells producing the lymphoproliferative cytokine, IL-2. In contrast, an inverse relationship was found with the frequencies of circulating CD4(+) and CD8(+) T cells displaying intermediate expression of the proliferation marker, Ki-67. Animals exposed to simian immunodeficiency virus (SIV) in utero appeared to have enhanced SIV-specific immune responses, a lower proportion of CD8(+) T cells expressing the exhaustion marker PD-1, and more circulating TH17 cells than controls. Although the development of tolerance was not demonstrated, these data suggest that rhesus monkeys exposed to SIVmac1A11 in utero had distinct immune responses associated with the control of viral replication after postnatal challenge.

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Authors

  • Chris A.R. Baker

  • Louise Swainson

  • Din L. Lin

  • Samson Wong

  • Dennis J. Hartigan-O'Connor

  • Jeffrey D. Lifson

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