HIV-1 virus takes advantage of immune cell signaling pathways in order to promote its replication according, to a new report published this week in Nature Immunology. The finding points to another potential vulnerability point whereby establishment of HIV-1 infection might be halted soon after initial exposure.
HIV-1, the virus that causes AIDS, is captured by antigen-presenting dendritic cells (DCs), which can transport the virus from mucosal entry sites to lymph nodes. It can be transferred to abundant CD4+ T cells ― its preferred host cell. Teunis Geijtenbeek and colleagues show that, in early stages of infection, HIV-1 promotes its own replication by utilizing two signaling pathways in DCs. One pathway is initiated by DC-SIGN ― a surface receptor that captures the virus and which triggers activation of a key transcription factor called NF-kappaB. A second signal, triggered by uncoating and capture of the HIV-1 viral genome, by an internal nucleic acid sensor leads to phosphorylation of another host protein called RNAPII. Both signals are required for RNAPII to generate full-length viral genome copies necessary for early viral replication. Interference of either pathway blocked establishment of HIV-1 infection in DCs and transmission to T cells.