The pathogenesis of West Nile virus-associated lymphohistiocytic proliferative cutaneous lesions of American alligators (Alligator mississippiensis)

"Pix" is one of the most common skin defects that reduce the quality of crocodilian leather. The name is derived from their resemblance to pit marks made by an ice pick. Histologically, each "pix" is associated with a focal dermal accumulation of immune cells, specifically lymphocytes and histiocytes. Consequently, these defects have been termed lymphohistiocytic proliferative cutaneous lesions (LPCLs). In farmed American alligators (Alligator mississippiensis), LPCLs have been associated with seropositivity against West Nile virus (WNV) and the presence of viral genome in the skin. Despite this association, the nature and pathogenesis of LPCLs remain unclear. Using immunohistochemistry and in situ hybridization, we unravel the microanatomy of LPCLs of alligators and localize WNV genome within the lesions. Our results show that LPCL lesions consist of de novo follicular aggregates of lymphocytes segregated into B- and T-cell zones, like tertiary lymphatic follicles of mammals and birds. Furthermore, the presence of WNV genome was highlighted by in situ hybridization in the macrophages of LPCLs, gut-associated lymphoid tissues, and the spleen. Our results suggest that LPCLs may form in American alligators’ skin as part of a generalized lymphofollicular proliferation, likely as an immune response against WNV infection.