6 research outputs found
Flt3L-Mediated expansion of plasmacytoid dendritic cells suppresses HIV infection in humanized mice
Plasmacytoid dendritic cells (plasmacytoid DC, pDC)
are major IFN-I producers and have been shown to be
affected by HIV through ill-defined mechanisms. In
this study, we directly assess the role of pDC in early
infection, evaluating whether modulating their abundance can alter viral replication. First, HIV infection
of humanized mice induces systemic depletion of
pDC, and in the presence of soluble FMS-like tyrosine
kinase 3 ligand (Flt3L), pDC levels remain elevated.
Flt3L significantly delays the onset of viremia and reduces viral replication via a process that is dependent
on pDC and mediated through an enhanced early
IFN-I response. pDC from Flt3L-treated mice are
more prone to express IFN-a following TLR7 stimulation, but this propensity is gradually decreased during
infection. In conclusion, maintaining pDC levels and
function is key to effective early viral control, and in
this context, these findings provide practical insights
for anti-HIV strategies and vaccine design
Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence
The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection