Extracellular
vesicles derived from Hepatitis-D Virus infected cells induce a
proinflammatory cytokine response in human peripheral blood mononuclear
cells and macrophages.
Hepatitis D Virus (HDV) is a satellite virus requiring a Hepatitis B
Virus (HBV) envelope proteins for productive infection. Hepatitis D is
the most severe form of viral hepatitis and is a global health threat
affecting 15 to 20 million humans. In contrast to the Hepatitis B Virus
mono-infection, against which only a minor innate immune response is
mounted at most, HBV-HDV coinfection is characterized by strong
activation of innate immune responses. To shed light on poorly
understood mechanisms of HDV-triggered disease progression, we focussed
on the question how immune cells may be activated by HDV. We
hypothesized that extracellular vesicles (EVs) released from infected
cells mediate this activation. We, therefore, purified EVs from the
supernatant of HDV-infected and non-infected cells and incubated them
with human peripheral blood mononuclear cells (PBMC) and macrophages.
Here we show for the first time that HDV infection leads to the
production of EVs which subsequently mediate a proinflammatory cytokine
response in primary human immune cells. These data might help to
understand how HDV can be sensed by non-infected immune cells.