Evolution of Viruses - Zhdanov V. M. 1990

Special Section
Coronaviruses

Coronaviruses comprise a small group of Viruses that infect mammals and birds, classified into a distinct family, Coronaviridae, with a single genus, Coronavirus [Закстельская Л. Я., 1982; Matthews R., 1982; Tyrrell D. et al., 1986].

The coronavirus genome is a single-stranded RNA with a Molecular Weight of 5.5×10⁶–6.1×10⁶ and positive polarity. A poly(A) tail is located at the 3'-end of the molecule, and a cap Structure is present at the 5'-end. Virions are spherical, 75–160 nm in diameter, featuring characteristic club-shaped projections (12x24 nm) on their outer envelope that form a crown-like appearance (hence the name). Enclosed within the outer envelope is a nucleocapsid composed of ribonucleoproteins with helical Symmetry, 11–13 nm in diameter (Fig. 18). Virions have a density of 1.18 g/ml, a size of 75–180 nm, consist of a core and an outer envelope, and contain 4–6 Proteins, including nucleoprotein, matrix proteins, and envelope Glycoproteins. Their molecular weight ranges from 15,000 to 200,000. The ribonucleoprotein protein with a molecular weight of 50,000 forms trimers with a mass of 140,000. Hemagglutinating properties are associated with envelope Antigens, and serological relationships exist among viruses within the genus. The virion composition includes a nucleocapsid phosphoprotein (50,000–60,000) and outer envelope glycoproteins E1 (20,000–35,000) and E2 (80,000–200,000), the latter forming club-shaped projections and exhibiting hemagglutinating activity. The genes are arranged on the virion RNA in the following order: 5'- 200,000 NS — 35,000 NS — E2 — 14,000 NS — E1 —N-3'.

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Fig. 18. Structure of a coronavirus (schematic diagram).

1 — lipid bilayer; E1, E2 — viral glycoproteins, where E2 forms peplomers and E1 interacts with the nucleocapsid; 2 - RNA; 3 — nucleocapsid proteins.

Following attachment to Cell Membrane Receptors, endocytosis, fusion of the viral and cellular membranes, and uncoating, the coronavirus genome becomes functional, inducing Protein Synthesis (primary METABOLISM/31.html">Transcription). At this stage, only the portion of The Genome adjacent to the 5'-end of the RNA is translated, encoding the synthesis (200,000). This peptide exhibits polymerase activity. Subsequently, a minus strand is synthesized, forming a replicative intermediate from which progeny RNA strands are produced. The minus strands serve as a template not only for the synthesis of progeny genomic RNAs, but also for 6 subgenomic RNAs with molecular weights ranging from 0.6×10⁶ to 3.7×10⁶. All of these mRNAs are synthesized from the same starting point at the 3'-end of the minus strand, with each longer strand encompassing the preceding, shorter one. However, their Translation occurs exclusively from the portion adjacent to the 5'-end. The 5'-end of the genomic RNA features cap structures attached to a leader sequence approximately 70 NUCLEOTIDES long. This sequence is present in all 6 mRNAs, apparently formed via splicing. Subgenomic RNAs possess cap structures and a poly(A) tail. Fig. 19 illustrates the synthesis scheme of these coronavirus RNAs. The regions originating from the 5'-ends are homologous. The Specific features of coronavirus Replication—the synthesis of subgenomic RNAs of varying sizes starting from the same origin—account for The high frequency of recombination observed when Cells are infected with two different strains of mouse hepatitis virus [Makino S. et al., 1986].

Six virion proteins are synthesized within the host cell: a large glycoprotein (gp84/90), a small glycoprotein gp31, a nucleocapsid phosphoprotein p51, two other major proteins p36 and p23, and a minor protein p28. Immunological analysis of coronavirus proteins isolated from various animals yielded the following findings. Bovine coronavirus proteins gp120, gp120, p52, and gp26 were found to be immunologically related to similar Proteins of the human coronavirus, but only to three proteins of the mouse coronavirus (hepatitis viruses): gp190, p52, and gp26 [Hogne B. et al., 1984]. Coronaviruses cause acute respiratory infections and enteritis in humans. In pigs, coronaviruses cause gastroenteritis and encephalitis; in calves, dogs, and cats, intestinal diseases; in rats, respiratory lesions; and in mice, hepatitis. Avian coronaviruses are the causative agents of infectious Bronchitis (chickens) and bluecomb disease (turkeys).

Fig. 19. Coronavirus replication (schematic diagram). Genomic RNA acts as mRNA and directs the synthesis of RNA polymerase, which synthesizes the minus-strand template. Plus-strand genomic RNA and subgenomic mRNAs are synthesized on the minus-strand template. Following translation, glycoproteins are transported to the Golgi apparatus, where glycosylation is completed. Virions bud into intracellular vacuoles. Values in parentheses represent molecular weights (×10³).

It is difficult to state anything definitive about THE ORIGIN OF coronaviruses. It is advisable to examine them in comparative terms with other enveloped viruses possessing a positive-sense single-stranded RNA genome, namely Togaviruses and Flaviviruses. Despite a shared genome strategy, all these groups exhibit significant differences of a, so to speak, tactical nature. In togaviruses, the portion of the genome adjacent to the 5'-end is translated first, which encodes the polymerase complex. Then, subgenomic RNA is synthesized (via a minus-strand intermediate), which encodes the structural proteins. Thus, the synthesis of early (nonstructural) proteins, RNA replication, and the synthesis of late (structural) proteins are temporally separated. In flaviviruses, despite the continuity of the genome, mRNAs are synthesized independently from each Gene, and genomic RNA replication also proceeds via a minus-strand synthesis stage. In coronaviruses, this process is more unique, occurring through the synthesis of minus strands of both the full genome (RNA replication) and subgenomic RNAs that originate from the same starting point and differ in length, and consequently in the number of genes. If we consider these differences to be tactical, The Emergence of the three families under Discussion can be viewed as three tactical variations of the same genomic strategy.

When examining the evolution of togaviruses, it was demonstrated that a similar strategy is observed in 4 groups of plant viruses (tomato spotted wilt virus, tobacco disease viruses, bromoviruses, and alfalfa mosaic virus). If these viruses are considered to be evolutionarily related, it is logical to include flaviviruses and coronaviruses among them as well. However, there is currently insufficient evidence for this, and dedicated studies are required to confirm or refute such a hypothesis. As for the evolution of coronaviruses, the driving forces and pathways of their evolution were likely similar to those described in Chapter 15 for Paramyxoviruses. Domesticated animals and house rodents probably served as the primary ecological niche for coronaviruses. Coronaviruses affecting humans could have "branched off" from these animal viruses. We currently know too little about these viruses to discuss the emergence of anthropozoonoses in greater detail.

It is also appropriate to mention here the isolation from horses in Bern (Switzerland) of an enveloped virus 120–140 nm in diameter with a helical nucleocapsid symmetry. In infected cells, the synthesis of two major proteins (22,000, 20,000) and 4 other proteins (200,000, 80,000–120,000, 32,000, 17,000) takes place. Despite some resemblance to coronaviruses, M. Horzinek et al. (1984) proposed classifying it into a separate family. Its genome is presumably positive-sense RNA. The elongated nucleoid forms an open ring with helical symmetry. The nucleocapsid protein has a molecular weight of 20,000. The outer envelope contains peplomeres. The virus shows no serological relationship with coronaviruses, but is serologically related to Breda virus (isolated from calf enteritis), the similar Lyon-4 virus, and a virus detected in human gastroenteritis. It has been proposed to group them into a distinct family, Toroviridae.