EARLY CYTOKINE AND CHEMOKINE GENE-EXPRESSION IN LYMPH-NODES OF MACAQUES INFECTED WITH SIMIAN IMMUNODEFICIENCY VIRUS IS PREDICTIVE OF DISEASE OUTCOME AND VACCINE EFFICACY

Competitive PCR was used to evaluate the expression of cytokine, grazy me B, and chemokine genes in lymph nodes of macaques recently infected with the simian immunodeficiency virus (SIV) pathogenic molecular clo ne SIVmac239 (n = 16), the nonpathogenic vaccine strain SIVmac239 Delt a nef (n = 8), and the nonpathogenic molecular clone SIVmac1A11 (n = 8 ), For both SIVmac239 and its nef-deleted derivative, strong expressio n was observed as early as 7 days postinfection for interleukin 1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13. The levels of gene induction were equally intense for both vir uses despite a lower viral load for SIVmac239 Delta nef compared with that for SIVmac239. However, the nature of the cytokine network activa tion varied with the viral inocula, Primary infection with SIVmac239 w as characterized by a higher level of IL-4, IL-10, MIP-1 alpha, MIP-1 beta, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239 Del ta nef. Thus, infection with nef-deleted SIV was associated with a pre ferential Th1 versus Th2 pattern of cytokine production, Infection wit h SIVmac1A11 was characterized by a delayed immune response for all ma rkers tested. The unique patterns of cytokine and chemokine gene expre ssion in lymph nodes correlated nicely with the pathogenic potential o f the SIV strains used as well as with differences in their ability to serve as protective vaccines.