Association of NF kappa B and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS

Abstract

Human gammaherpesvirus 8 (HHV-8) replication is influenced by a complex interaction between viral and host elements. Here, we evaluated the expression of NF kappa B and TNF-alpha in B (CD19 +) and T (CD3 +) lymphocytes, and the serum concentration of IL-1 beta and IL-12 cytokines in people living with HIV/AIDS (PLHA), negative for HHV-8-related diseases, and who presented antibodies to latent or lytic antigens from HHV-8. In addition, we also evaluated the correlation of HHV-8 viral load with NF kappa B, TNF-alpha, IL-1 beta and IL-12 levels. The expression of NF kappa B (p < 0.0001) or TNF-alpha (p < 0.0001) in B lymphocytes (CD19 +) and the IL-1 beta (p < 0.0266) and IL-12 (p < 0.0001) concentrations were associated with the presence of antibodies to HHV-8 lytic antigens. The CD19 + NF kappa B + TNF-alpha + and CD3 + NF kappa B + TNF-alpha + cells were also associated with the presence of antibodies to lytic infection (p < 0.0001). Among all PLHA evaluated, only individuals with the highest titers of lytic antibodies, i.e., 1:320, had detectable HHV-8 viral load. In these, HHV-8 viral load was correlated to NF kappa B (r = 0.6, p = 0.003) and TNF-alpha (r = 0.5, p = 0.01) (both in CD19 + lymphocytes) and with IL-1 beta (r = 0.5, p = 0.01) and IL-12 (r = 0.6, p = 0.006) levels. We believe that viral replication and/or reactivation, in addition to being associated with the development of lytic antibodies against HHV-8, may be associated with inflammatory response via NF kappa B. Finally, although immune response imbalance has been previously related to HHV-8-associated diseases, our results indicate that important changes in immunity, mainly in the inflammatory response, may be clearly observed in individuals with HHV-8, but who have not yet presented clinical manifestations.