title: Serum apoptosis markers in HIV-infected patients with human herpesvirus type 8 and herpes simplex virus type 2 co-infection.
abstract: 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.
authors: University Hospital for Infectious Diseases Dr. Fran Mihaljevic, Mirogojska 8, 10000, Zagreb, Croatia. orode@bfm.hr
authors: O
authors: O
authors: Dakovic Rode
authors: A
authors: A
authors: Markotic
authors: M
authors: M
authors: Kujundzic Tiljak
authors: S
authors: S
authors: Zidovec Lepej
authors: J
authors: J
authors: Begovac
mesh_terms: D000328:Adult; D000367:Age Factors; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood*; D060085:Coinfection / Q000473:pathology*; D003430:Cross-Sectional Studies; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D015497:HIV-1 / Q000472:pathogenicity; D006566:Herpesviridae Infections / Q000473:pathology*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D019014:fas Receptor / Q000097:blood
chemical_list: D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor