INTRODUCTION
Coronaviruses are large, enveloped RNA viruses. The human coronaviruses cause common colds, may cause lower respiratory tract infections, and have been implicated in gastroenteritis in infants. Novel coronaviruses have been identified as the cause of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Animal coronaviruses cause diseases of economic importance in domestic animals. Coronaviruses of lower animals establish persistent infections in their natural hosts. The human viruses are difficult to culture and therefore are more poorly characterized.
PROPERTIES OF CORONAVIRUSES
Important properties of the coronaviruses are listed in Table 41-1.
| Virion: Spherical, 120–160 nm in diameter, helical nucleocapsid |
| Genome: Single-stranded RNA, linear, nonsegmented, positive-sense, 27–32 kb, capped and polyadenylated, infectious |
| Proteins: Two glycoproteins and one phosphoprotein. Some viruses contain a third glycoprotein (hemagglutinin esterase) |
| Envelope: Contains large, widely spaced, club- or petal-shaped spikes |
| Replication: Cytoplasm; particles mature by budding into endoplasmic reticulum and Golgi |
Outstanding characteristics: Cause colds, SARS, and MERS Display high frequency of recombination Difficult to grow in cell culture |
Coronaviruses are enveloped, 120- to 160-nm particles that contain an unsegmented genome of single-stranded positive-sense RNA (27–32 kb), the largest genome among RNA viruses. The genomes are polyadenylated at the 3′ end. Isolated genomic RNA is infectious. The helical nucleocapsid is 9–11 nm in diameter. There are 20-nm-long club- or petal-shaped projections that are widely spaced on the outer surface of the envelope, suggestive of a solar corona (Figure 41-1). The viral structural proteins include a 50–60 kDa phosphorylated nucleocapsid (N) protein, a 20–35 kDa membrane (M) glycoprotein that serves as a matrix protein embedded in the envelope lipid bilayer and interacting with the nucleocapsid, and the spike (S; 180–220 kDa) glycoprotein that makes up the petal-shaped peplomers. Some viruses, including human coronavirus OC43 (HCoV-OC43), contain a third glycoprotein (HE; 65 kDa) that causes hemagglutination and has acetylesterase activity.
The genome organizations of a representative coronavirus is shown in Figure 41-2. The gene order for the proteins encoded by all coronaviruses is Pol-S-E-M-N-3′. Several open reading frames encoding nonstructural proteins and the HE protein differ in number and gene order among coronaviruses. The SARS virus contains a comparatively large number of interspersed genes for nonstructural proteins at the 3′ end of the genome.
Figure 41-2
Genomic organization of coronaviruses. The SARS coronavirus (SARS-CoV) genome is about 29.7 kb. Boxes shaded in yellow represent open reading frames (ORFs) encoding structural proteins; boxes shaded in lavender encode nonstructural proteins. The separate ORFs within each gene are translated from a single mRNA species. S, spike; E, envelope; M, transmembrane; N, nucleocapsid. The ORF1 cleavage products are designated nsp1–16 and include a phosphatase, cysteine proteinases, an RNA-dependent RNA polymerase, a helicase, and an endoribonuclease. (Adapted with permission from Lai MMC, Perlman S, Anderson LJ: Coronaviridae. In Knipe DM, Howley PM [editors-in-chief]. Fields Virology, 5th ed. Lippincott Williams and Wilkins, 2007.)
The Coronaviridae is one of two families, along with Arteriviridae, within the order Nidovirales. Characteristics used to classify Coronaviridae include particle morphology, unique RNA replication strategy, genome organization, and nucleotide sequence homology. There are two subfamilies (Coronavirinae and Torovirinae) and six genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, Deltacoronavirus, Bafinivirus, and Torovirus) in the Coronaviridae family. The first two and the last genera contain viruses able to infect humans. The toroviruses are widespread in ungulates and appear to be associated with diarrheal disease.
There are six coronaviruses that can infect humans, the alpha coronaviruses 229E and NL63 and the beta coronaviruses OC43, HKU1, SARS-CoV, and MERS-CoV. There are many coronaviruses that infect animals, with most infecting one or a few species.
Because human coronaviruses do not grow well in cell culture, details of viral replication have come from studies with mouse hepatitis virus, which is closely related to human strain OC43 (Figure 41-3). The replication cycle takes place in the cytoplasm of cells.
