We previously investigated the role of
Nitazoxanide (
NTZ), a thiazolide endowed with
antiviral and
antiparasitic activity, in HIV-1
infection.
NTZ treatment in primary isolated PBMCs was able to reduce HIV-1
infection in vitro by inducing the expression of a number of
type-I interferon-stimulated genes. Among them,
NTZ was able to induce cholesterol-25-hydroxylase (CH25H), which is involved in
cholesterol metabolism. In the present study, we wanted to deepen our knowledge about the
antiviral mechanism of action of
NTZ. Indeed, by inducing CH25H, which catalyzes the formation of
25-hydroxycholesterol from
cholesterol,
NTZ treatment repressed
cholesterol biosynthetic pathways and promoted
cholesterol mobilization and efflux from the cell. Such effects were even more pronounced upon stimulation with FLU
antigens in combination. It is already well known how lipid metabolism and virus replication are tightly interconnected; thus, it is not surprising that the
antiviral immune response employs genes related to
cholesterol metabolism. Indeed,
NTZ was able to modulate
cholesterol metabolism in vitro and, by doing so, enhance the
antiviral response. These results give us the chance to speculate about the suitability of
NTZ as adjuvant for induction of specific natural immunity. Moreover, the putative application of
NTZ to alimentary-related diseases should be investigated.