Heterogeneity of gene expression of the hemagglutinin-esterase (HE) protein of murine coronaviruses

Abstract

The hemagglutinin-esterase (HE) membrane glycoprotein is present only in some members of the coronavirus family, including some strains of mouse hepatitis virus (MHV). In the JHM strain of MHV, expression of the HE gene is variable and corresponds to the number of copies of a UCUAA pentanucleotide sequence present at the 3'-end of the leader RNA. This copy number varies among MHV strains, depending on their passage history. The JHM isolates with two copies of UCUAA in their leader RNA showed a high level of HE expression, whereas the JHM isolate with three copies had a low-level expression. In this study, the analysis of HE gene expression was extended to other MHV strains. The synthesis of HE mRNA in these viruses also correlates with the copy number of UCUAA in the leader RNA and the particular intergenic sequence preceding the HE gene. In one MHV strain, MHV-1, no detectable HE mRNA was synthesized, despite the presence of a proper transcription initiation signal. This lack of HE mRNA expression was consistent with a leader RNA containing three UCUAA copies. However, mutations and deletions within the coding region of the MHV-1 HE gene have generated a stretch of sequence which resembled the transcriptional initiation motif, and was shown to initiate the synthesis of a novel smaller mRNA. These findings strengthened the theory that interactions between leader RNA and transcriptional initiation sequences regulate MHV subgenomic mRNA transcription. Sequence analysis revealed that most MHV strains, through extensive mutations, deletions, or insertions, have lost the complete HE open reading frame, thus turning HE into a pseudogene. This high degree of variation is unusual as the other three structural proteins (spike, membrane, and nucleocapsid) are well-maintained. In contrast to bovine coronavirus, which apparently requires HE for viral replication, the HE protein in MHV may be only an accessory protein which is not necessary for viral replication. JHM and MHV-S, however, have preserved the expression of HE protein.

Crystal Structure of Bovine Coronavirus Spike Protein Lectin Domain

“…Consistent with the existence of a viral lectin in their spike proteins, BCoV and HCoV-OC43 also encode a hemagglutinin-esterase that functions as a receptor-destroying enzyme and aids viral detachment from sugar on infected cells (25). MHV also contains a hemagglutinin-esterase gene in its genome, but only some of the MHV strains actively express the hemagglutinin-esterase protein (26). These observations raise interesting questions about the origin and evolution of coronavirus spike protein lectin domains.…”

Mouse Hepatitis Virus

“…Therefore, most images of MHV are partly "bald." Some, but not all, strains of MHV possess HE proteins (Yokomori et al 1991(Yokomori et al , 1989. The genome encodes nucleocapsid phosphoprotein (N), which forms tubular nucleocapsid strands that bind to viral RNA and lie within the lipoprotein envelope that is formed by budding from intracellular membranes (Sturman and Holmes 1985;Tooze and Tooze 1985).…”

The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

“…These isoforms contain either 4 or 2 immunoglobulin-like domains, a transmembrane domain, and different cytoplasmic tails. Different isoforms can be expressed together, and the pattern of expression of different isoforms may vary in different tissues (Huang, et al, 1990 ;1991, Yokomori andLai, 1992a The first member of the family of carcinoembryonic antigen (CEA) was originally identified as a marker for human tumors (Gold and Freedman, 1965 (Huitric, et al, 1976) . The BGP proteins are found in Fig.…”

“…MHV-JHM express a th i rd glycoprotein, called hemagglutininesterase (HE) (Luytjes, et al, 1988;Yokomori, et al, 1991) . This 65 -70 kDa protein forms a disulfide-linked dimer in the viral envelope (King, et al, 1985) .…”