Disease relevance of M

• In previous work with the coronavirus mouse hepatitis virus (MHV), a highly defective M protein mutant, MDelta2, was constructed [1].
• Thus, it was the packaging signal that mediated the selective interaction between M protein and viral RNA to drive the specific packaging of RNA into virus particles [2].
• The M protein of mouse hepatitis virus (MHV) is an integral membrane protein with a short ectodomain, three transmembrane segments, and a large carboxy-terminal endodomain facing the interior of the viral envelope [3].
• Thus, the SARS-CoV 3a protein is an O-glycosylated glycoprotein, like the group 2 coronavirus M proteins but unlike the SARS-CoV M protein, which is N glycosylated [4].
• The data also suggest that response to the M protein is important in preventing disease progression in C57BL/6 mice since cells which recognize this protein are absent from persistently infected mice [5].

High impact information on M

• Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein [6].
• Complementary biochemical experiments were carried out to determine whether vesicular transport was required for the newly synthesized M protein, that contains only O-linked oligosaccharides, to acquire first, GalNAc and second, the Golgi modifications galactose and sialic acid [7].
• The results from both in vivo studies and from the use of SLO-permeabilized cells showed that, while GalNAc addition occurred under conditions which block vesicular transport, both cytosol and ATP were prerequisites for the M protein oligosaccharides to acquire Golgi modifications [7].
• Moreover, a mutant of the M protein lacking the 22 COOH-terminal amino acids, that is transported to the plasma membrane, gave rise to similar complexes, albeit smaller in size, that persisted at the plasma membrane [8].
• Using pulse-chase analyses we studied the oligomerization of the M protein in sucrose gradients [8].

Chemical compound and disease context of M

• The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein [9].

Biological context of M

• The M protein-nucleocapsid interaction, which occurred near or at the MHV budding site, most probably represented the process of specific packaging of the MHV genome into MHV particles [10].
• Conversely, the M protein expressed in mammalian cells did not induce apoptosis [11].
• Since glycosylation of the M protein is not required for virus assembly, the oligosaccharides are likely to be involved in the virus-host interaction [12].
• Thirty-four percent of its amino acid sequence is homologous with the M protein of the bovine coronavirus (BCV), 32% with that of the mouse hepatitis coronavirus (MHV), and 19% with that of the avian infectious bronchitis coronavirus (IBV) [13].
• The AflII site engineered between ORFs 5 and 6 was subsequently used to generate a virus in which the ectodomain of the ORF 6-encoded M protein was extended with nine amino acids derived from the extreme N-terminus of the homologous protein of mouse hepatitis virus (MHV; family Coronaviridae, order Nidovirales) [14].

Anatomical context of M

• Identification of a CD4+ T cell epitope within the M protein of a neurotropic coronavirus [15].
• When mRNA from infected cells, or RNA prepared by in vitro transcription of the reconstructed M gene, was translated in vitro in the presence of microsomes, the M protein became translocated and glycosylated [13].
• The microtubule disruption is attributed to two amino acid differences in M protein [16].
• Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of alpha IFN by porcine blood leukocytes [17].

Associations of M with chemical compounds

• In contrast, folding and transport of the M protein were not inhibited by DTT [18].

Physical interactions of M

• Pulse-labeling experiments showed that newly synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi compartment, which is part of the MHV budding site [10].

Other interactions of M

• Analysis of second-site revertants of MDelta2 revealed mutations in the carboxy-terminal region of the N protein that compensated for the defect in the M protein [1].
• Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13-877 of the S protein [19].

References