Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIV?nef Vaccination: e0149491

• Published in: PloS one Vol. 11; no. 2
• Main Authors: Guerra-Perez, Natalia, Aravantinou, Meropi, Veglia, Filippo, Goode, Diana, Truong, Rosaline, Derby, Nina, Blanchard, James, Grasperge, Brooke, Gettie, Agegnehu, Robbiani, Melissa
• Format: Journal Article
• Language: English
• Published: 01.02.2016
• Subjects: Herpesviridae; Lentivirus; Macaca; Retroviridae
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0149491

Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239 delta nef (SIV delta nef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIV delta nef-infected animals. Rectal SIV delta nef infection/vaccination protected 7 out of 7 SIV delta nef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIV delta nef-negative macaques), while 1 out of 3 animals co-infected with SIV delta nef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.