In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission

Early events in retrovirus transmission are determined by interactions
between incoming viruses and frontline cells near entry sites. Despite
their importance for retroviral pathogenesis, very little is known about
these events. We developed a bioluminescence imaging (BLI)-guided
multiscale imaging approach to study these events in vivo. Engineered
murine leukemia reporter viruses allowed us to monitor individual stages
of retrovirus life cycle including virus particle flow, virus entry into
cells, infection and spread for retroorbital, subcutaneous and oral
routes. BLI permitted temporal tracking of orally administered
retroviruses along the gastrointestinal tract as they traversed the lumen
through Peyer’s Patches to reach the draining mesenteric sac. Importantly,
capture and acquisition of lymph-, blood- and milk-borne retroviruses
spanning three routes, was promoted by a common host factor, the I-type
lectin CD169, expressed on sentinel macrophages. These results highlight
how retroviruses co-opt the immune surveillance function of tissue
resident sentinel macrophages for establishing infection.