Pathogenesis of wild-type- and vaccine-based recombinant peste des petits ruminants virus (PPRV) expressing EGFP in experimentally infected domestic goats

Abstract

Peste des petits ruminants virus (PPRV) is a highly contagious morbillivirus related to measles and canine distemper virus, mostly affecting small ruminants. The corresponding PPR disease has a high clinical impact in goats and is characterized by fever, oral and nasal erosions, diarrhoea and pneumonia. In addition, massive infection of lymphoid tissues causes lymphopaenia and immune suppression. This results in increased susceptibility to secondary bacterial infections, explaining the observed high mortality in some outbreaks. We studied the pathogenesis of PPR by experimental inoculation of Dutch domestic goats with a recombinant virulent PPRV strain modified to express EGFP and compared it to an EGFP-expressing vaccine strain of PPRV. After intratracheal inoculation with virulent PPRV, animals developed fever, viraemia and leucopaenia, and shed virus from the respiratory and gastro-intestinal tracts. Macroscopic evaluation of fluorescence at the peak of infection 7 days post-inoculation (dpi) showed prominent PPRV infection of the respiratory tract, lymphoid tissues, gastro-intestinal tract, mucosae and skin. Flow cytometry of PBMCs collected over time demonstrated a cell-associated viraemia mediated by infected lymphocytes. At 14 dpi, pathognomonic zebra stripes were detected in the mucosa of the large intestine. In contrast, vaccine strain-inoculated goats remained largely macroscopically fluorescence negative and did not present clinical signs. A low-level viraemia was detected by flow cytometry, but at necropsy no histological lesions were observed. Animals from both groups seroconverted as early as 7 dpi and sera efficiently neutralized virulent PPRV in vitro. Combined, this work presents a study of the pathogenesis of wild type- and vaccine-based PPRV in its natural host. This study shows the strength of recombinant EGFP-expressing viruses in fluorescence-guided pathogenesis studies.

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“…Due to intensive multiplication there is necrosis of tissues inside the lymph node and destruction of leukocytes, which leads to the development of immunosuppression. Similar conclusions were obtained by K. Schmitz et al (2023), who indicate that massive infection of lymphoid tissues causes immune suppression. This leads to increased susceptibility to secondary bacterial infections.…”

A sporadic case of small ruminant plague in sheep: morphological and functional manifestation of cellular and humoral immunodeficiency

“…Due to intensive multiplication there is necrosis of tissues inside the lymph node and destruction of leukocytes, which leads to the development of immunosuppression. Similar conclusions were obtained by K. Schmitz et al (2023), who indicate that massive infection of lymphoid tissues causes immune suppression. This leads to increased susceptibility to secondary bacterial infections.…”

Inoculation of raccoons with a wild-type-based recombinant canine distemper virus results in viremia, lymphopenia, fever, and widespread histological lesions

“…Morbilliviruses of other target species follow similar replication kinetics, for example, peste des petits ruminant virus in goats and the non-fatal feline morbillivirus (FeMV) in cats. The low levels of infected WBC in peripheral blood after FeMV infection (<0.5%) are reflected in the low case fatality rates after acute infection, which further supports the role of replication kinetics on disease outcome ( 29 , 30 ). Based on the rapid virus replication, persistent viremia, invasion of the CNS, increasing viral shedding (and no clearance), absent or low serological responses, and unresolved lymphopenia we observed in raccoons, we speculate that none of the animals would have survived over the course of a longer study period; however, longer-term studies are required to confirm this.…”