Pathology and Pathogenesis of Eurasian Blackbirds (Turdus merula) Naturally Infected with Usutu Virus

Abstract

The Usutu virus (USUV) is a mosquito-borne zoonotic flavivirus. Despite its continuous circulation in Europe, knowledge on the pathology, cellular and tissue tropism and pathogenetic potential of different circulating viral lineages is still fragmentary. Here, macroscopic and microscopic evaluations are performed in association with the study of cell and tissue tropism and comparison of lesion severity of two circulating virus lineages (Europe 3; Africa 3) in 160 Eurasian blackbirds (Turdus merula) in the Netherlands. Results confirm hepatosplenomegaly, coagulative necrosis and lymphoplasmacytic inflammation as major patterns of lesions and, for the first time, vasculitis as a novel virus-associated lesion. A USUV and Plasmodium spp. co-infection was commonly identified. The virus was associated with lesions by immunohistochemistry and was reported most commonly in endothelial cells and blood circulating and tissue mononucleated cells, suggesting them as a major route of entry and spread. A tropism for mononuclear phagocytes cells was further supported by viral labeling in multinucleated giant cells. The involvement of ganglionic neurons and epithelial cells of the gastrointestinal tract suggests a possible role of oral transmission, while the involvement of feather follicle shafts and bulbs suggests their use as a diagnostic sample for live bird testing. Finally, results suggest similar pathogenicity for the two circulating lineages.

The Interferon Response Dampens the Usutu Virus Infection-Associated Increase in Glycolysis

“…The high USUV-permissiveness of the TME-R cell line is in agreement with the in vivo susceptibility of Eurasian blackbirds (Giglia et al, 2021). Additionally, we have also addressed the potential adaptation of USUV to lung carcinoma A549 cells as a commonly used type II pulmonary epithelial cell model.…”

Combining host and vector data informs emergence and potential impact of an Usutu virus outbreak in UK wild birds

“…PMEs supported an alternative cause of death in all captive birds, with no unexplained mortality or lesions suggestive of USUV infection (e.g. hepatosplenomegaly 4 ).…”

“…Based on the experience of wild bird mortality caused by USUV in mainland Europe (e.g. 4 , 9 , 10 ), the syndromic surveillance categories generalised ill health and neurological disease were considered of particular interest as a potential signal of infection. However, USUV could not be excluded as a possible underlying cause for DIRs categorised as musculoskeletal disease, trauma, predation, drowning or tick parasitism, or where blackbirds were found dead with no observed clinical signs.…”

“…USUV has an enzootic cycle with transmission between mosquito vectors and birds as the main amplifying hosts 3 . Whilst a variety of predominantly passerine hosts are susceptible, epizootic mortality of wild birds due to USUV has principally affected Eurasian blackbirds ( Turdus merula ) 4 and on a scale sufficient to cause population decline in some countries (e.g. Germany 5 ).…”

“…Molecular screening for Plasmodium spp. was performed to appraise factors affecting host health, since avian malaria has been described as a comorbidity with USUV infection in wild birds 4 , 8 . Finally, mosquito blood meal analyses were conducted to explore local host feeding to inform potential species at risk of USUV exposure and advance understanding of USUV transmission networks.…”