481 EBV Infection can Enhance IL-7 Production and Up-regulate the Replication of HIV Y. Okamoto*1, D. Douek1, G.B. Di Russo2, R.A. Koup1 1Vaccine Res Ctr NIH, Bethesda, MD and 2Children's Natl Med Ctr, Washington, DC
Background: IL-7 is an epithelial cell-derived lymphoid-specific cytokine known to regulate lymphocyte development and homeostasis. Recent data indicate that plasma IL-7 levels are strongly correlated with T-lymphopenia and viral load and may be associated with disease progression in HIV-infected individuals. Here we examined the effects of EBV infection on IL-7 production and HIV replication.
Methods: Ten (10) EBV-transformed peripheral B-cell lines (B-LCL), one thymic B-LCL, and primary B-cells were cultured for 3 days, and the culture supernatants were measured for IL-7 levels by ELISA. To examine the effects of EBV on HIV infection in thymus, thymic organ culture (TOC) were infected with B98-5 supernatant dialyzed to remove cytotoxic factors, and then infected with X4-or R5-tropic HIV.
Results: EBV-infected peripheral B-cells (PB) began to produce IL-7 5 days after infection. All of the 10 EBV-transformed B-LCL produced higher levels of IL-7 (4.85 ± 2.15 pg/ml per 106 cells) when compared with PBMC (0.08 pg/ml per 106 cells) or PB (0.63 pg/ml per 106 cell). EBV-transformed thymic B-cells also produced high levels of IL-7 (2.75 pg/ml per 106 cells) . Although EBV has been reported to infect epithelial cells, EBV-exposed thymic epithelial cells did not enhance IL-7 production. EBV latent membrane protein-1 (LMP-1)+CD20+ cells were detected in EBV-infected TOC at day 9 by FACS. TOC infected with EBV and X4-tropic HIV showed higher P24 levels at day 5 of infection (= day 9 of EBV infection) when compared with TOC infected with HIV alone in 5 different experiments.
Conclusions: We demonstrated that peripheral or thymic B-cells produce IL-7 in response to EBV infection. EBV infection in HIV-infected TOC up-regulated HIV replication. This may occur through induction of IL-7. Functional loss of EBV-specific CD8+ T-cells occurs in HIV infection and correlates with an increase in EBV load. Thus EBV may be associated plasma IL-7 levels and HIV progression.