The coronavirus family (Coronaviridae) is a positive-sense single-stranded RNA, with a size of 27 kb. These viruses have a potential species specificity and interspecies transmission. The interspecies transmission of viruses from one host species to another is a major factor responsible for the majority of emerging and reemerging infections. The Coronaviridae is one of the most popular emerging viral families that threaten to the public health.
Middle East respiratory syndrome coronavirus
severe acute respiratory syndrome coronavirus
infectious bronchitis virus
The Coronaviridae have a global distribution. Most of the humans coronavirus (CoV) infectious have a serious effect. The Coronaviridae includes several animals and human viruses causing a serious epidemies and endemics, as such the severe acute respiratory syndrome (SARS) CoV (SARS-CoV) outbreak in 2003 and the CoV respiratory syndrome outbreak in 2012-14. Severe CoV acute respiratory virus (SARS-CoV) infection and the Middle East respiratory syndrome (MERS) CoV (MERS-CoV) in humans in 2012 caused severe lower respiratory tract disease as well as IBV (infectious bronchitis virus) in the avian and poultry field.
Emergent and Reemerging Viral Infections
An emerging infectious disease is defined as an infectious disease whose incidence has increased over the past 20 years and may increase in the future. Emerging infections account for more than 10% of human diseases (Mackey et al., 2014). An emerging pathogen may be defined as an infectious agent whose frequency or geographic range increases following its first introduction into a new host population, while a reemerging pathogen is one whose incidence or geographic distribution is increasing in an existing host population as a result of long-term changes in its underlying epidemiology. The emergence of pathogens may be based on subjective criteria, which may reflect increasing awareness, improved diagnosis, discovery of previously unrecognized infectious agents as well as any objective epidemiological data (Woolhouse, 2002, Engering et al., 2013).
Many viruses are classified as emerging pathogens according to the WHO, including MERS-CoV, SARS-CoV, and IBV that are the focus of this work.
Phylogenetically, Coronaviridae belongs to Nidovirales in group IV, with a single genomic RNA fragment, oriented in a positive direction.
Nidovirales is an order that contains four families (Arteriviridae, Coronaviridae, Mesoniviridae, and Roniviridae) according to the genomic classification (Fig. 7.1) (Cavanagh, 1997). The name Nidovirales originates from the fact that the viruses belonging to this order have the capacity to produce during infection a 3′-multiplexed complex of subgenomic messenger RNA (mRNA), hence the word “nidus” in Latin, which means to nest (De Vries et al., 1997).
Although the first CoV, IBV, was discovered in 1932 (Hudson and Beaudette, 1932), Coronaviridae was proposed as a taxonomic family 30 years later after the discovery of human CoV in humans, patients with cold (Tyrrell and Bynoe, 1965, Tyrrell et al., 1975).
In recent years, Coronaviridae have been considered among the most popular viral families because a number of its members were responsible for several human and animal epidemiological pathologies. These include the murine epidemic in 2005 (Weiss and Navas-Martin, 2005), the SARS in 2003 (Fleck, 2003), the SARS pandemic in 2015-16 in Russia and Ukraine (Berger, 2017), the MERS-CoV 2012-17 (WHO2), and the CoV IBV (Riedel, 2006).
CoVs have diverse host ranges (Fig. 7.3). They affect most terrestrial and marine animals and humans, including dolphins, birds, cattle, woodpeckers, fish, etc. It has been shown that a virus can infect various hosts, for example, SARS and MERS-CoV (Wang et al., 2005, Tang et al., 2006, Belouzard et al., 2012).
Genomic Organization and Proteomics of Coronaviridae
Coronaviridae is positive RNA viruses with an unsegmented genome of 26-33 kb in length. They are generally of similar genomic and structural construction, containing 5′-end ORF series that encode nonstructural proteins that are primarily involved in pathogenicity. The number of ORFs differs by species, and it has a significant portion of Coronaviridae genomes, followed by the coding regions of structural proteins, more than two-thirds of the CoV genome is composed of an open reading code (ORF) coding for the replicase polyprotein 1a/1b, and the remainder contains ORFs encoding the structural proteins: spicules (S), envelope (E), membrane (M), nucleoprotein (N), and a variable collection of accessory proteins (Woo et al., 2009, Liu et al., 2014) (Fig. 7.4).
CoVs encode membrane-associated proteins that are incorporated into virions: spike (S), envelope (E), membrane (M), and nucleoprotein (N). These four proteins occur in the S-E-M-N order in all known CoV lineages (Woo et al., 2014).
Among the spike envelope membrane and nucleoprotein (SEMN) genes, CoVs encode species-specific accessory proteins, many of which appear to be incorporated into virions at low levels, ranging from an accessory in alpha-CoVs, including human CoV NL63 (Pyrc et al., 2004), to nine accessories provided in gamma- CoV HKU22 (Woo et al., 2014). The genomic position of these accessory genes varies with S-encoded accessories in some beta-CoV, between S and E in most lineages, between M and N in most lineages, and after N rarely in alpha-CoVs and gamma-CoV and commonly in delta-CoVs. The M gene seems to follow the E gene directly through Coronaviridae, although there is no obvious transcriptional or transrational reason for which this should necessarily be the case (Fig. 7.5).
Gene Responsible for Pathogenicity
Protein S plays a key role in the power of pathogenicity. This glycoprotein (S) is an important component in the species specificity, pathogenesis, and escape of immunity. Like human immunodeficiency virus (HIV) gp160, influenza hemagglutinin, and Ebola virus glycoprotein, the CoV spike (S) glycoprotein protein is a class I viral fusion protein that mediates virus binding and fusion, allowing virus to enter the host cell (Xu et al., 2004). Like other class I fusion proteins, the S-glycoprotein contains two functional domains, S1 and S2, linked by a protease cleavage site (Xu et al., 2004). The S1 domain (17-756aa) contains the receptor-binding domain (RBD) (318-510aa) while the S2 region (757-1225aa) contains the two heptad repeat (HR) regions that facilitate viral fusion and a transmembrane domain (1189-1227aa) which anchors the tip on the viral envelope (Xu et al., 2004). CoVs are thought to accumulate in cells by the following sequence of events: cell-receptor binding ACE2, DPP4, and APN to affect tropism in the cell by endocytosis and cleavage of SARS-CoV S by cathepsin-cell protease. L causes a rearrangement of S1 and S2 subunits inducing fusion of the viral membrane and the host to deposit the viral/nucleocapsid genome complex in the cytoplasm where replication occurs.
The glycoprotein of CoV S is an essential element of species specificity, which is also the main determinant of pathogenesis because a virus that is incapable of infection is unlikely to cause disease. Using reverse genetics, the substitution of mouse hepatitis virus (MHV) protein S for feline infectious peritonitis virus protein S alone was sufficient for the murine tropic virus to infect feline cells. In less extreme examples the host range of CoV can be modulated by a few point mutations in S-glycoprotein that focuses either in RBD or in the fusogenic domain (de Haan et al., 2005).
Although the earlier CoV dogma suggests that expansion of the host range is mediated by mutation in the S1 region, McRoy et al. reported an expansion of the host range of MHV that may also be mediated by changes in the host range, amino acids in fusion equipment of the S2 region. A prime and relevant example of a CoV host range change due to mutations in the S1 region was observed during the evolution of the SARS-CoV epidemic strain, SARS Urbani (de Haan et al., 2005)
The SARS-CoV (S) peak gene sequences isolated from human cases during the early phase of the epidemic in 2002-03 and during the reemergence of 2003-04 are very similar to strain SZ16. SZ16 was isolated from palm tree crops in live animal markets in the Guangdong region of China during the outbreak, and its protein S differs from the epidemic strain, SARS Urbani, in 18 amino acids, 16 of which are in the S1 domain containing the RBD. The crystalline structure of ACE2-receptor-bound SARS-CoV RBD and biochemical experimentation demonstrated that the critical amino acids (K479, T487) in the SZ16 S civet RBD inhibited its binding to the human ACE2 receptor (hACE2), thereby providing a block in the expansion of host range and human pathogenesis (Sheahan and Baric, 2010). Using a pseudotyped retrovirus with mutant or wild versions of the zoonotic (SZ16) or epidemic (Urbani) glycoprotein, Li et al. demonstrated that K479 and T487 were critical residues inhibiting the binding of the civet tip to the hACE2 receptor.
Unfortunately, the pseudotyped system is able to evaluate the efficiency of binding and entry, but not the growth kinetics of the virus. By using recombinant SARS-CoV carrying a variety of zoonotic, epidermal intermediate S-glycoproteins in a one-step growth pattern, data on binding, entry, and growth can be elucidated. In addition, infection of the cells expressing the civet (cACE2) or hACE2 of the SARS-CoV receptor with recombinant variants of SARS-CoV S-glycoproteins makes it possible to study the ability to grow and use receptors in both the amplifier and the epidemic host. In evaluating the growth of the SARS glycoprotein variant in CACE2 or hACE2 cell cultures, we deduced that the epidemic strain retained growth ability in cell cultures expressed by CACE2 and hACE2 (Sheahan and Baric, 2010).
Emerging and Reemerging Viral Pathogens
Volume 1: Fundamental and Basic Virology Aspects of Human, Animal and Plant Pathogens
2020, Pages 127-149