Characterization and Comparison of SLAM/CD150 in Free-Ranging Coyotes, Raccoons, and Skunks in Illinois for Elucidation of Canine Distemper Virus Disease

Abstract

Canine distemper virus (CDV) is a cause of significant disease in canids and increasingly recognized as a multi-host pathogen, particularly of non-canid families within Carnivora. CDV outbreaks in sympatric mesocarnivores are routinely diagnosed in the Forest Preserve District of Cook County, Illinois. CDV is diagnosed more commonly and the disease more severe in raccoons and striped skunks than in coyotes. Research in other species suggests host cell receptors may play a role in variable disease outcome, particularly, the signaling lymphocyte activation molecule (SLAM) located on lymphoid cells. To evaluate receptor differences, partial SLAM genes were sequenced, and predicted amino acid (AA) sequences and structural models of the proposed viral interface assessed. Of 263 aligned nucleotide base pairs, 36 differed between species with 24/36 differences between canid and non-canids. Raccoon and skunk predicted AA sequences had higher homology than coyote and raccoon/skunk sequences and 8/11 residue differences were between coyote and raccoons/skunks. Though protein structure was similar, few residue differences were associated with charge and electrostatic potential surface alterations between canids and non-canids. RNAScope®(Advanced Cell Diagnostics, Silicon Valley, USA) ISH revealed low levels of expression that did not differ significantly between species or tissue type. Results suggest that differences in host receptors may impact species-specific disease manifestation.

First report of canine morbillivirus infection of adipose tissue-derived stem cells from dogs with distemper

“…In that regard, although it was not the purpose of this study, we consider that ASCs may not have any of the receptors recognized by the virus, including the SLAM receptor -which is ** found in thymocytes, activated lymphocytes T and B, dendritic cells, and macrophages -the Nectin-4 receptor, which is found in epithelial cells [31][32][33], or a potential third receptor, as in what may be present in astrocytes which do not display the aforementioned receptors [34].…”

Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review

“…The extracellular region of SLAM contains a variable (V) domain and a constant (C2) Ig-like domain. The V domain is required for recognition and binding to the CDV H protein [ 36 , 39 ]. SLAM participates in various immune functions, including the costimulation of T cells and B cells, the secretion of IFN by Th1 cells, and the inhibition of B-cell apoptosis [ 40 ].…”

“…SLAM receptors often exhibit species differences, resulting in differences in CDV tropism. Nectin-4 is also a common CDV receptor, but critical residues of the H protein required for nectin-4 binding are highly conserved [ 39 ]. Considering the potential differences in CDV infectivity and pathogenicity based on viral–host cell interactions, further investigation into host cell receptors in a variety of CDV-susceptible carnivores is warranted [ 39 ].…”

“…Nectin-4 is also a common CDV receptor, but critical residues of the H protein required for nectin-4 binding are highly conserved [ 39 ]. Considering the potential differences in CDV infectivity and pathogenicity based on viral–host cell interactions, further investigation into host cell receptors in a variety of CDV-susceptible carnivores is warranted [ 39 ]. Further, CDV can adapt to related host species via mutations in the receptor-binding region of the H protein for enhanced virulence.…”

Sylvatic Canine Morbillivirus in Captive Panthera Highlights Viral Promiscuity and the Need for Better Prevention Strategies

“…All these sites have been subject of speculation regarding the CDV’s ability to jump species, particularly to non-canids [ 27 , 28 , 29 , 30 ]. However, an ever growing number of authors see no significant difference among residues in multi-host strains or virus-targeted host receptors [ 19 , 26 , 31 , 32 , 33 ], but rather, pleiotropic and temporal, sometimes concurrent, geographical clades seem to be the cause for outbreaks and CDV evolution [ 23 , 33 , 34 , 35 ]. Nonetheless, though H-gene has been largely used for phylogenetic studies, full genome phylogenetic trees are increasingly preferred and have helped identify other genetic sites where recombination may play a significant role in CDV evolution [ 24 , 36 ].…”