Synergistic HIV-1 Activation by Gingival Resident Cell Factors and Periodontopathogens

Numerous bacteria and host factors that occur during co-infections in HIV-1 infected patients regulate HIV-1 recrudescence from latently infected cells. These appear to influence HAART failure and AIDS progression, Objective: We determined the ability of factors produced by gingival resident cells [epithelial (OKF4), fibroblasts (HGF)] in response to periodontopathogenic bacteria and evaluated any synergism between host factors and the bacteria in HIV-1 LTR activation in monocytes/macrophages (BF24), Methods: OKF4 or HGF cell cultures were challenged with extracts of F. nucleatum (Fn), P. gingivalis (Pg), or T. denticola (Td) to elicit mediator production. Using a CAT colorimetric assay, OKF4 and HGF supernatants were examined for their ability to enhance HIV-1 LTR/CAT activation in BF24 cells, either in absence or presence of challenge with the bacterial extracts, Results: Both OKF4 and HGF supernatants showed enhanced HIV-1 LTR/CAT activation in a time and microorganism dependent manner particularly related to Fn challenge. These supernatants, in presence of all three bacteria, generally enhanced a synergistic HIV-1 LTR/CAT activation. Bacterial pre-exposure of OKF4 cells did not increase this synergism, although this was observed for HGF factors, Conclusions: Soluble mediators produced by OKF4 & HGF in response to periodontopathogens can contribute to HIV-1 LTR/CAT activation in BF24 cells, in addition to reactivation by direct interaction of BF24 with bacteria. These results suggest that both gingival resident cells and microbial components associated with periodontal disease could contribute to promoting HIV-1 reactivation in the oral environment. Supported by P20 RR020145 from the NCRR.