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A Bmp Reporter with Ultrasensitive Characteristics Reveals That High Bmp Signaling Is Not Required for Cortical Hem Fate

  • Author(s): Doan, Linda T
  • Javier, Anna L
  • Furr, Nicole M
  • Nguyen, Kevin L
  • Cho, Ken W
  • Monuki, Edwin S
  • Schubert, Michael
  • et al.
Abstract

Background: Herpes simplex virus type 2 (HSV-2), the mostfrequent cause of genital ulcer disease (GUD), has been shown to play a moreimportant role than any other sexually transmitted infections (STIs) in drivingHIV prevalence in Africa. In turn, HIV-1 infection leads to more frequent HSV-2reactivations and shedding. The exact immune mechanisms involved in thisvirological negative immuno-synergy are unknown. In the present study we soughtto assess whether HIV co-infection would affects HSV-specific T cell immunity.Methods: Nineteen HSV peptides, derived from HSV-2glycoproteins gB and gD, were used to analyze the frequency and the magnitudeof HSV-2-specific IFN-γ-producing CD4+ and CD8+ T cellresponses in 30 HSV-2 seropositive patients and 17 HSV-2 seronegativeindividuals in a cohort of heterosexual Senegalese HIV-discordant couples,using ELISpot assay. HIV RNA viral load has been run for HIV infected subjects and CD4 count ran for all subjects using a flow cytometry method..Results: The magnitude and frequency HSV-2-specific Tcell responses was compared between 21 HSV-2 co-infected with HIV-1 and 9 HSV-2mono-infected individuals. A significantly higher magnitude of IFN-γ-producingT cell responses were observed in HSV-2 infected patients compared toseronegative individuals (median, 61 vs. 0 spots/106 PBMC, P= 0.001). Moreover, twenty-four (80%) out of 30 HSV-2 seropositive patientsshowed significant HSV-2-specific IFN-γ-producing T cell responses comparedwith only 6 (35%) out of 17 HSV-2 negative subjects (P < 0.001). TheHSV-2 mono-infected patients showed significantly higher magnitude ofHSV-2-specific T cell responses compared to HSV/HIV co-infected patients(median, 140 vs. 42 spots/106 PBMC, P = 0.024).Conclusions: Our finding suggest that co-infection with HIV-1 inHSV-2-infected patients might be associated with reduced HSV-2 cellular immuneresponses. However, the interaction between HIV and HSV-2 appears complex, andprecise longitudinal studies will be required to dissect their exact temporalrelationship.

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