Organ tropism of murine coronavirus does not correlate with the expression levels of the membrane-anchored or secreted isoforms of the carcinoembryonic antigen-related cell adhesion molecule 1 receptor

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is the sole known receptor of murine hepatitis virus (MHV) A59, but the available, often qualitative, data about CEACAM1 expression does not explain MHV organ tropism. Ceacam1 transcripts undergo alternative splicing resulting in multiple isoforms, including secreted CEACAM1 isoforms that can neutralize the virus. We determined the quantities of Ceacam1 transcripts encoding membranebound and secreted isoforms in mouse organs and a set of cell lines. In vivo, the lowest receptor mRNA levels were found in brain and muscle and these were similar to those in easily infectable cultured cells. While the quantities of the receptor transcripts varied between mouse organs, their abundance did not correlate with susceptibility to MHV infection. The proportion of transcripts encoding secreted isoforms also could not explain the selection of sites for virus replication, as it was constant in all organs. Our data suggest that neither of the two CEACAM1 isoforms defines MHV organ tropism.

Identification and Characterization of a Proteolytically Primed Form of the Murine Coronavirus Spike Proteins after Fusion with the Target Cell

“…However, a given protease inhibitor may not block all individual proteases of a specific class, and our inhibitor panel was lacking threonine protease inhibitors and aminopeptidase inhibitors that potentially prime the S protein (44). Plasticity in cleavage is further supported by the similarity of S protein processing in various cell lines and may confer flexibility to the virus in infecting different tissues (45). Alternatively, heterogeneous S2* fragment could be explained in analogy to filovirus fusion protein processing, which requires gradual trimming by low-pH-activated endosomal proteases to reach fusion competence (46).…”

Up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 in gastrointestinal cancer and its clinical relevance

“…As such, the CEACAM1-L isoform is functionally inhibitory and the most commonly reported isoform [25]. In most cell types and tissues, CEACAM1-L and CEACAM1-S are expressed together, but at characteristically different ratios [26,27]. However, very little information is available concerning the CEACAM1 isoform expression patterns in cancer.…”