Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus)

Abstract

Lassa fever (LF) survivors develop various clinical manifestations including polyserositis, myalgia, epididymitis, and hearing loss weeks to months after recovery from acute infection. We demonstrate a systemic lymphoplasmacytic and histiocytic arteritis and periarteritis in guinea pigs more than 2 months after recovery from acute Lassa virus (LASV) infection. LASV was detected in the arterial tunica media smooth muscle cells by immunohistochemistry, in situ hybridization, and transmission electron microscopy. Our results suggest that the sequelae of LASV infection may be due to virus persistence resulting in systemic vascular damage. These findings shed light on the pathogenesis of LASV sequelae in convalescent human survivors.

Keywords: Arenaviridae; BSL-4; Lassa virus persistent infection; arenavirus; arteritis; guinea pig; mammarenavirus; periarteritis; viral hemorrhagic fever.

Figure 1.

Representative images of histopathology, immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy. (A) Histopathology of severe lymphoplasmacytic and histiocytic arteritis and periarteritis of a coronary artery in the heart from strain 13 guinea pigs (GP_S13) 2 inoculated with wild-type Lassa virus Josiah strain (wtLASV-J), days postinfection (dpi) 41. Hematoxylin and eosin stain: (B) IHC demonstrates that the smooth muscle cells in the tunica media of the mesenteric artery are strong positive for LASV antigen (black arrows, red chromogen), from GP_S13 2 inoculated with wtLASV-J, dpi 41; (C) the smooth muscle cells in the tunica media of the mesenteric artery from GP_S13 2 inoculated with wtLASV-J, dpi 41, are positive (black arrow, red chromogen) for LASV genomic ribonucleic acid by ISH; (D) electron micrograph from the tunica media of an artery in the pancreas from GP_S13 2 exposed to wtLASV-J, dpi 41. Lassa virions (black arrows) were approximately 100 nm in diameter and had granular cores. Budding virus particles were seen (black arrowhead).