HIV-1 infection and induction of interferon alpha in plasmacytoid dendritic cells.

Purpose of review Loss of blood plasmacytoid dendritic cell (pDC) in HIV-1 infection is thought to impact on adaptive immune responses whilst the virus also induces aberrant interferon alpha (IFN-alpha) production that may fuel chronic immune activation and drive disease progression. Recent attention has focussed on the pathway of HIV-induced IFN-alpha production by pDC and the new data are reviewed here together with the pathway leading to infection. Recent findings Attachment to CD4 and chemokine co-receptors is essential for HIV-1 infection. Although CD4, but not co-receptor binding, is a major route for passage to endosomes and triggering of IFN-alpha secretion this may also occur by CD4-independent mechanisms involving other receptors. In contrast to other Toll-like receptor (TLR)-7 ligands and RNA viruses that stimulate pDC to secrete IFN-alpha for 2-3h, HIV-1-stimulated pDC can give sustained IFN-alpha production for up to 48 h which may contribute to chronic immune activation. This may reflect retention of HIV in early endosomes which also seems to be associated with incomplete maturation induced by HIV. Summary HIV-1-pDC interactions contribute to pathogenesis through depletion and aberrant IFN-alpha production. New data on the pathway of pDC HIV-stimulated IFN-alpha secretion may facilitate therapy to reduce chronic immune activation and slow disease progression.