Serum apoptosis markers in HIV-infected patients with human herpesvirus type 8 and herpes simplex virus type 2 co-infection

  • O. Dakovic RodeEmail author
  • A. Markotic
  • M. Kujundzic Tiljak
  • S. Zidovec Lepej
  • J. Begovac


This study aimed to examine the influence of human herpesvirus type 8 (HHV-8) and herpes simplex virus type 2 (HSV-2) co-infections on apoptosis serum markers in human immunodeficiency virus (HIV)-infected patients. Sera from 110 HIV-infected and 59 HIV-uninfected individuals were analyzed for soluble Fas (sFas), sFas ligand (sFasL), caspase-8, and Bcl-2. The findings of HIV-infected patients with no co-infection (n = 37), HIV-infected patients with HHV-8 co-infection (n = 22), HIV-infected patients with HSV-2 co-infection (n = 51), and patients with HSV-2 co-infection and no HIV infection (n = 20) were compared to controls (reference group) with no HIV, HSV-2, and HHV-8 co-infections (n = 39). Soluble Fas and sFasL concentrations were the highest in HIV and HHV-8 co-infected patients (medians, 912.7 pg/ml and 74.3 pg/mL, respectively). No difference in caspase-8 concentrations was found, whereas Bcl-2 concentrations were the highest in HIV and HHV-8 co-infected individuals. Older age was associated with higher sFas (p < 0.001) and lower sFasL (p = 0.04) concentrations. In a robust regression model adjusted for age, the log-transformed sFas concentrations were significantly lower in HIV-infected patients with no co-infections (β = −0.244; p < 0.001) and higher in HIV and HHV-8 co-infected patients (β = 0.216; p = 0.012) compared to the reference group. Soluble FasL was significantly lower in HIV-infected patients with no co-infections (β = −0.284; p = 0.005) and in HIV-infected patients with HSV-2 co-infection (β = −0.381; p < 0.001) compared to the reference group. Soluble FasL was also higher in HIV and HHV-8 co-infected patients compared to controls (β = 0.248; p = 0.036). Our results suggest that HHV-8 and HSV-2 may have a significant effect on Fas–FasL-mediated apoptosis in HIV-1 patients. HHV-8 upregulates while HSV-2 downregulates sFas and sFasL.


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Human Immunodeficiency Virus Patient Soluble FasL sFas Concentration 
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Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • O. Dakovic Rode
    • 1
    Email author
  • A. Markotic
    • 1
  • M. Kujundzic Tiljak
    • 2
    • 3
  • S. Zidovec Lepej
    • 1
  • J. Begovac
    • 1
    • 2
  1. 1.University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”ZagrebCroatia
  2. 2.University of Zagreb, School of MedicineZagrebCroatia
  3. 3.Andrija Štampar School of Public HealthZagrebCroatia

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