Construction and In Vitro Properties of Chimeric Simian and Human Immunodeficiency Virus with the Human TNF-Alpha Gene

Tumor necrosis factor‐alpha (TNF‐α) has been reported to be involved in the development and progression of acquired immunodeficiency syndrome (AIDS). To study the role of this cytokine in AIDS pathogenesis, we constructed a chimeric simian and human immunodeficiency virus (SHIV) having the human TNF‐α gene (SHIV‐TNF) and characterized its properties in vitro. SHIV‐TNF replicated both in M8166, a human T cell line, and in monkey peripheral blood mononuclear cells (PBMCs). Along with SHIV‐TNF replication, TNF‐α was detected in the culture supernatant by ELISA. The maximum expression level of TNF‐α reached 120 ng/ml in M8166 cells, and 2.5 ng/ml in monkey PBMCs. The expressed TNF was biologically active, as shown by a cytotoxic assay using TNF‐sensitive L929 mouse fibroblasts. This activity was detected at least until 10 passages of SHIV‐TNF (74 days after the initial infection). In monkey PBMCs, SHIV‐TNF replicated much better than the parental SHIV‐NI. Flow cytometric analysis showed that the death of monkey PBMCs infected with SHIV‐TNF was severer than that caused by the parental SHIV‐NI. These results suggest that SHIV‐TNF would be useful for inducing the disease in a monkey model, which may contribute to a better understanding of the role of TNF‐α in AIDS etiology.