Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus

Abstract

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

Animal Models of Lassa Fever

“…Laryngitis and heterophilic tracheitis were noted in guinea pigs exposed via aerosol [35]. Interstitial pneumonia was found in all moribund animals with an increase in mononuclear cells, especially macrophages, surrounding the blood vessels and airways [34,35,37,39]. Edema and hemorrhage were also noted in the lungs with an expansion of the alveolar septae [35,39].…”

“…Inbred Strain 13 domesticated guinea pigs have been used as a lethal LF rodent model for studying pathogenesis as well as antiviral, vaccine, and immunotherapy candidates. Unlike their Hartley outbred counterpart, this model does not require virus adaptation [34,35] (Table 3). However, Inbred Strain 13 guinea pigs are not readily available, limiting their use as a LF animal model.…”

“…Neutralizing antibodies were not produced [37]. Signs of disease included weight loss, fever, ruffled fur, hunched posture, altered mentation, and conjunctivitis [34][35][36]. Guinea pigs typically became moribund between 10 and 15 dpi [37].…”

“…The highest viral load was identified in the lung, followed by the spleen, pancreas, lymph nodes, adrenal glands, kidneys, salivary glands, liver, and heart [34,35,39]. Histological findings included the presence of viral antigen typically associated with hepatitis, hepatic cell death, hair follicle epithelium cell death, and adrenal cortical necrosis [35]. Laryngitis and heterophilic tracheitis were noted in guinea pigs exposed via aerosol [35].…”

“…Histological findings included the presence of viral antigen typically associated with hepatitis, hepatic cell death, hair follicle epithelium cell death, and adrenal cortical necrosis [35]. Laryngitis and heterophilic tracheitis were noted in guinea pigs exposed via aerosol [35]. Interstitial pneumonia was found in all moribund animals with an increase in mononuclear cells, especially macrophages, surrounding the blood vessels and airways [34,35,37,39].…”