Serpentoviruses: More than Respiratory Pathogens

Abstract

<jats:p>In recent years nidoviruses have emerged as important respiratory pathogens of reptiles, affecting captive python populations. In pythons, nidovirus (recently reclassified as serpentovirus) infection induces an inflammation of the upper respiratory and alimentary tract which can develop into a severe, often fatal proliferative pneumonia. We observed pyogranulomatous and fibrinonecrotic lesions in organ systems other than the respiratory tract during full post mortem examinations on 30 serpentovirus RT-PCR positive pythons of varying species originating from Switzerland and Spain. The observations prompted us to study whether this not yet reported wider distribution of lesions is associated with previously unknown serpentoviruses or changes in the serpentovirus genome. RT-PCR and inoculation of <jats:italic>Morelia viridis</jats:italic> cell cultures served to recruit the cases and obtain virus isolates. Immunohistochemistry and immunofluorescence staining against serpentovirus nucleoprotein demonstrated that the virus not only infects a broad spectrum of epithelia (respiratory and alimentary epithelium, hepatocytes, renal tubules, pancreatic ducts etc.), but also intravascular monocytes, intralesional macrophages and endothelial cells. By next-generation sequencing we obtained full length genome for a novel serpentovirus species circulating in Switzerland. Analysis of viral genomes recovered from pythons showing serpentovirus infection associated respiratory or systemic disease did not reveal sequence association to phenotypes, however, functional studies with different strains are needed to confirm this observation. The results indicate that serpentoviruses have a broad cell and tissue tropism, further suggesting that the course of infection could vary and involve lesions in a broad spectrum of tissues and organ systems as a consequence of monocyte-mediated viral systemic spread.</jats:p> <jats:p><jats:bold>IMPORTANCE</jats:bold> During the last years, python nidoviruses (now reclassified as serpentoviruses) have become a primary cause of fatal disease in pythons. Serpentoviruses represent a threat to captive snake collections, as they spread rapidly and can be associated with high morbidity and mortality. Our study indicates that, different from previous evidence, the viruses do not only affect the respiratory tract, but can spread in the entire body with blood monocytes, have a broad spectrum of target cells, and can induce a variety of lesions. Nidovirales is an order of animal and human viruses that compromise important zoonotic pathogens such as MERS-CoV, SARS-CoV, and SARS-CoV-2. Serpentoviruses belong to the same order as the mentioned human viruses and show similar characteristics (rapid spread, respiratory and gastrointestinal tropism, etc.). The present study confirms the relevance of natural animal diseases to better understand the complexity of viruses of the order nidovirales.</jats:p>

Nidoviruses in Reptiles: A Review

“…Experimental infection of P. regius resulted in histological findings consistent with a chronic-active mucinous rhinitis, stomatitis, tracheitis, oesophagitis, and proliferative interstitial pneumonia ( 55 ). The proliferative interstitial pneumonia has been a consistent finding in clinical cases of nidovirus infection in snakes and has more recently been called “nidovirus associated proliferative disease—NPD” ( 16 , 57 ).…”

“…Stenglein et al ( 16 ) identified virus in liver, kidney, heart, spleen, and brain, but largely at levels 3–5 orders of magnitude lower than the lung. More recently, during multiple necropsies ( n = 30) Dervas et al ( 57 ) identified pyogranulomatous and fibrinonecrotic lesions in organ systems aside from the respiratory tract suggesting a much broader cell and tissue tropism. Virus was also detected in epithelial cells (alimentary, hepatic, renal, pancreatic), intravascular monocytes, intralesional macrophages, and endothelial cells ( 57 ).…”

“…More recently, during multiple necropsies ( n = 30) Dervas et al ( 57 ) identified pyogranulomatous and fibrinonecrotic lesions in organ systems aside from the respiratory tract suggesting a much broader cell and tissue tropism. Virus was also detected in epithelial cells (alimentary, hepatic, renal, pancreatic), intravascular monocytes, intralesional macrophages, and endothelial cells ( 57 ). Dervas et al ( 57 ) also identified animals with evidence of disseminated granulomatous and/or fibrinonecrotic lesions, vascular and perivascular lesions, and infected monocytes.…”

“…Virus was also detected in epithelial cells (alimentary, hepatic, renal, pancreatic), intravascular monocytes, intralesional macrophages, and endothelial cells ( 57 ). Dervas et al ( 57 ) also identified animals with evidence of disseminated granulomatous and/or fibrinonecrotic lesions, vascular and perivascular lesions, and infected monocytes. These lesions were more predominant in Morelia spp.…”

Serpentovirus (Nidovirus) and Orthoreovirus Coinfection in Captive Veiled Chameleons (Chamaeleo calyptratus) with Respiratory Disease

“…In a previous study, some pythons that were consecutively tested for over two years were continuously positive for serpentovirus but never exhibited clinical signs during this time [ 16 ]. In a separate study, systemic lesions associated with viral infection were observed in some pythons without clinical or histologic evidence of respiratory disease [ 34 ]. The findings in chameleons could represent similar phenomena as some animals shown to be infected did not develop disease, even over the three months prior to culling for herd health, and exhibited minimal to no histologic lesions (VC7, 8, 9).…”