Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

Natalia Guerra-Pérez,Meropi Aravantinou,Elena Martinelli,James Blanchard,Agegnehu Gettie,Melissa Robbiani,Brooke Grasperge,Diana Goode,Rosaline Truong,Nina Derby,Filippo Veglia

doi:10.1371/journal.pone.0149491

Natalia Guerra-Pérez, Meropi Aravantinou + Show 9 more

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https://doi.org/10.1371/journal.pone.0149491

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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 SIVmac239Δnef (SIVΔnef) 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 SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques), while 1 out of 3 animals co-infected with SIVΔnef 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.

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Prevalent Herpes Simplex Virus type 2 (HSV-2) infection is associated with a 2- to 4-fold increased risk of Human Immunodeficiency Virus (HIV) acquisition[1,2,3]
In order to understand the impact of rectal HSV-2 infection on the susceptibility to rectal SIVmac239wt and on the ability of SIVΔNef rectal vaccination to protect from SIVmac239wt infection, we devised a four-arm study with 32 macaques (Fig 1A)
Group I: 9 animals were inoculated rectally with 3000 TCID50 of SIVΔNef, 12 weeks later they were challenged with 4x108 pfu of HSV-2 rectally and 3 weeks later, they were challenged rectally with 3000 TCID50 of SIVmac239wt; group II: 9 animals were challenged with HSV-2 and 3 weeks later with SIVmac239wt; group III: 8 animals were inoculated with SIVΔNef and weeks later challenged with SIVmac239wt; group IV: 6 animals were challenged rectally with SIVmac239wt in parallel to the other groups as controls

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Prevalent Herpes Simplex Virus type 2 (HSV-2) infection is associated with a 2- to 4-fold increased risk of Human Immunodeficiency Virus (HIV) acquisition[1,2,3]. This can be partially explained by the presence of genital and rectal ulcers and inflammation at the site of HSV-2 infection in symptomatic subjects, the association remains in asymptomatic subjects in absence of detectable active HSV-2 replication [3,4,5,6]. The impact of rectal HSV-2 infection on rectal SIV acquisition is understudied

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