Cutaneous dendritic cells are main targets in acute HIV-1-infection

Acute human immunodeficiency virus (HIV) infection is a transient illness t hat typically presents with mucocutaneous and constitutional symptoms. It i s soon followed by seroconversion with the detection of anti-HIV antibodies in the peripheral blood. To better understand the pathogenetic events lead ing to this clinical picture, we sought to investigate the (immuno)histolog ic features of the skin rash occurring in an acutely infected person. A ski n biopsy of an acutely infected person was investigated histologically and immunohistologically using paraffin-embedded tissue sections. Interface der matitis with pronounced vacuolization of the basal keratinocytes was a prom inent histological finding. The inflammatory infiltrate was composed of CD3 +/CD8+ T cells with coexpression of Granzyme B7 and TIA-1, and CD68+ histio cytes/dendritic cells. CD1a+ intraepidermal Langerhans cells (LC) were sign ificantly decreased and individual LC coexpressed HIV-p24 antigens as evide nced in double labeling experiments. HIV-infected LC were demonstrated in c lose apposition to cytotoxic T cells. This study provides the first definitive evidence for infection of LC at ex tramucosal sites in this very early stage of disease. Our findings emphasiz e the critical role of dendritic cells as a virus reservoir and the skin as a major site of HIV replication during the course of the disease.