Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission

  1. Donald L. Sodorad
  1. aDepartment of Virology and Immunology
  2. bSouthwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA
  3. cDental School, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  4. dSeattle Biomed, Seattle, Washington, USA
  1. Fig 1
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    Fig 1

    Mucosal inflammatory cytokines associated with gingivitis. GCF samples were taken from rhesus macaques before (day 1) and 34 days after induction of gingivitis (GVS) by teeth ligation and a diet of softened food; GCF samples were also taken from control animals (CNT) at the same time points. Cytokine concentrations (in pg/ml) were determined in the GCF by an NHP Luminex assay as described in Materials and Methods; differences in median cytokine concentrations were compared between groups with the Mann-Whitney test.

  2. Fig 2
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    Fig 2

    Clinical manifestation of gingivitis. Untreated controls and monkeys after 5 weeks of teeth ligature and a diet of soft food were evaluated for plaque index, probing depth, bleeding index, and attachment loss as described in Materials and Methods. Median values for both groups were compared by the Mann-Whitney test.

  3. Fig 3
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    Fig 3

    Viral loads in rhesus macaques after oral exposure to SIV. Control macaques and animals that developed gingivitis after 5 weeks of tooth ligature were exposed to SIVmac251 by the oral route as described in Materials and Methods. Viral loads were determined by the NASBA method in RNA extracted from plasma of infected macaques and are expressed as genome equivalents (geq)/ml. WPI, weeks postinfection.

  4. Fig 4
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    Fig 4

    Mucosal cytokines induced by SIV infection. GCF samples (two samples per animal) were taken from gingivitis (GVS; triangles) and control (CNT; circles) rhesus macaques on the day of SIV challenge (DOC) and at 2, 4, and 26 weeks post-SIV oral exposure (WPC). SIV-infected macaques are represented by filled symbols, while open symbols are uninfected macaques. Cytokine concentrations (in pg/ml) were determined in the GCF by an NHP Luminex assay as described in Materials and Methods. Differences in median cytokine concentrations were compared between groups with the Mann-Whitney test. ***, extremely significant, P < 0.001; **, very significant, 0.001 < P < 0.01; *, significant, 0.01 < P < 0.05; ns, not significant, P > 0.05.

  5. Fig 5
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    Fig 5

    Inflammatory gene expression levels in oral mucosa. RNA was extracted from oral biopsy specimens obtained from gingivitis (GVS; triangles) and control macaques (CNT; circles) before oral exposure to SIV and at 2 and 4 weeks post-SIV infection (WPC). Levels of mRNA for IP-10 and OAS were determined by real-time RT-PCR using GAPDH levels as a reference. Differences in relative mRNA levels were compared between groups with the Mann-Whitney test. ***, extremely significant, P < 0.001; **, very significant, 0.001 < P < 0.01; *, significant, 0.01 < P < 0.05; ns, not significant, P > 0.05.

  6. Fig 6
    View larger version:
    Fig 6

    Mucosal inflammatory cytokines associated with SIV infection. GCF samples (two samples per animal) were taken from gingivitis (GVS; triangles) and control (CNT; circles) rhesus macaques on the day of SIV challenge (DOC) and at 2, 4, and 26 weeks post-SIV oral exposure (WPC). SIV-infected macaques are represented by filled symbols, while open symbols are uninfected macaques. Cytokine concentrations (in pg/ml) were determined in the GCF by an NHP Luminex assay as described in Materials and Methods. Differences in median cytokine concentrations were compared between groups with the Mann-Whitney test. ***, extremely significant, P < 0.001; **, very significant, 0.001 < P < 0.01; *, significant, 0.01 < P < 0.05; ns, not significant, P > 0.05.

  7. Fig 7
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    Fig 7

    Systemic inflammatory cytokines associated with SIV infection. Plasma samples from gingivitis (GVS; triangles) and control (CNT; circles) macaques were obtained before oral exposure to SIV (DOC) and at 2, 4, and 8 weeks post-SIV infection (WPC). Cytokine concentrations (in pg/ml) were determined by an NHP Luminex assay as described in Materials and Methods. Differences in median cytokine concentrations were compared between groups with the Mann-Whitney test. ***, extremely significant, P < 0.001; **, very significant, 0.001 < P < 0.01; *, significant, 0.01 < P < 0.05; ns, not significant, P > 0.05.

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This Article

  1. Accepted manuscript posted online 21 November 2012, doi: 10.1128/JVI.02079-12 J. Virol. vol. 87 no. 3 1750-1758
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