Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09
pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with
pantetheinase activity involved in recycling
coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1
infection, we investigated the change of VNN1 expression in the context of IAV
infection and the effects of its related substances, i.e., its direct substrate
pantetheine and its two metabolites
pantothenic acid and
cysteamine on the replication of IAV in the human alveolar epithelial
carcinoma cell line A549. The
messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV
infection under an elevated concentration of
pantetheine. Moreover, VNN1
mRNA levels were elevated by > 100-fold in response to pro-inflammatory
cytokines, especially TNF-α and IL-1β.
Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1)
mRNA levels when it was administered prior to and during
infection. In addition,
cysteamine treatment during IAV
infection significantly reduced the viral replication and IAV M1
mRNA levels, whereas
pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1
pantetheinase plays a suppressive role in IAV
infection in the respiratory tract, especially in severe conditions under
hypercytokinemia.