Human herpesvirus-6 (HHV-6) is an important immunosuppressive and immnnomodulatory virus that primarily infects immune cells (mainly CD4(+) T cells) and strongly suppresses the proliferation of infected cells.Toll-like receptors are pattern-recognition receptors essential for the development of an appropriate innate immune defense against infection.To understand the role of CD4(+) T cells in the innate response to HHV-6 infection and the involvement of TLRs, we used an in vitro infection model and observed that the infection of CD4(+) T cells resulted in the activation of JNK/SAPK via up-regulation of toll-like receptor 9(TLR9).Associated with JNK activation, annexin Ⅴ-PI staining indicated that HHV-6A was a strong inducer of apoptosis.Apoptotic response associated cytokines, IL-6 and TNF-α also induced by HHV-6A infection.