Lesions were not evident upon HSV-2/SHIV-RT co-challenge.
Vaginal and cervical pinch biopsies were collected 3 12 months post-HSV-2/SHIV-RT co-challenge.
After co-challenge these responses increased (Fig. 4A, left panel; HSV-2-specific responses were not monitored in SHIV-RT-infected SHIV-RT-infected SHIV-RT-infected
A possible ligand effect of HSV-2 exposure in the co-challenge cannot be excluded based on the way these experiments were performed.
Local cytokine and chemokine responses were further monitored over the first 6 weeks of HSV-2/SHIV-RT co-challenge and compared to the responses seen in naïve animals infected solely with SHIV-RT.
The somewhat delayed local IL2 and CCL5 and lower CCL3 responses observed after co-challenge of HSV-2-infected macaques compared to those detected after SHIV-RT infection of naïve animals, suggest that HSV-2 impaired the responses to SHIV-RT.
In an attempt to reactivate and increase HSV-2 DNA shedding as further proof of HSV-2 infection, cervical and vaginal pinch biopsies (2 4 each) were taken from 8 animals approximately 3 6 (Biopsy 1) and 9 12 (Biopsy 2) months after HSV-2/SHIV-RT co-challenge (once infected with SHIV-RT; approximately 15 24 months post primary HSV-2 exposure).
PC-817 was tested for its ability to prevent vaginal SHIV-RT infection when applied 30 minutes or 24 hours prior to co-challenge of HSV-2-exposed animals with HSV-2 and SHIV-RT (Fig. 6) vs a placebo control gel, MC.
In order to determine if HSV-2-exposed macaques exhibited increased susceptibility to immunodeficiency virus infection (like humans), we co-challenged HSV-2-infected animals with HSV-2 and SHIV-RT.
The rationale for first exposing animals to HSV-2 and then co-challenging them with HSV-2 and SHIV-RT was to give us the best chance of getting HSV-2 infection (with the limited numbers of animals available for this study), since this is something that has not documented previously.
This depolarizing effect upon NS309-calcium co-challenge was also visible, although to a lesser extent, in mouse brain synaptosomes.
