Tropism of Tanapox virus infection in primary human cells.

Tanapox virus (TPV) belongs to the genus Yatapoxvirus and causes a relatively benign zoonotic disease in man, with symptoms that resemble a mild version of human monkeypox. In order to investigate the underlying mechanisms of TPV pathogenesis, the tropism and replication characteristics of TPV were examined in a variety of primary human cells. A GFP expressing TPV (TPV-GFP) was constructed and used to infect primary human dermal fibroblasts (pHDFs) and peripheral blood mononuclear cells (PBMCs), both of which are believed to be major in vivo targets of poxvirus infection. pHDFs fully supported productive replication and cell-cell spread of TPV-GFP. However, induction of cell cycle arrest in pHDFs by contact mediated inhibition or rapamycin treatment eliminated the ability of TPV to fully stimulate cell cycle progression and dramatically reduced viral replication. TPV-GFP-infected human PBMCs were screened for permissiveness by FACS analysis. CD14+ cells (monocytes) were the primary cellular target for TPV infection. A small proportion of CD3+ cells (T cells) were positive for GFP expression, yet TPV was not able to replicate and spread in cultured peripheral blood lymphocytes, regardless of their state of activation. Primary human monocytes, however, demonstrated robust TPV replication, yet these cells no longer supported replication of TPV once they differentiated into macrophages. This unique ex vivo tropism of TPV gives key insights into the basis for the self-limiting pathogenicity of TPV in man.

Multiple anti-cytokine activities secreted from tanapox virus-infected cells.

Tanapox virus (TPV) produces a mild disease in humans characterized by transient fever, one or more nodular skin lesions and regional lymphadenopathy. We demonstrate that TPV-infected cells, but not mock-infected cells, secrete an early 38 kDa glycopeptide that, unlike any other known protein, binds to human (h) interferon-gamma, hIL-2 and hIL-5. In concomitant experiments this polypeptide failed to bind to hIL-1 alpha, hIL-3, hIL-4, hIL-6, hIL-7, hIL-8 or hIL-10. Inhibition of hIL-2 and hIL-5 biological activities were demonstrated using a hIL-2-dependent mouse T cell line (HT-2) and a hIL-5-dependent erythroleukemia cell line (TF-1), respectively. The 38 kDa polypeptide also inhibited the bioactivity of interferon-gamma. Taken together, our results suggest that TPV has evolved multiple pathways to disarm both TH1 cell-mediated (IL-2 and interferon-gamma) and TH2-associated (IL-5) immune responses for its infectivity with remarkable genetic economy.