Human Coronavirus
Last Updated 12-Jan-2006

The Human Coronavirus Family

Order:
Nidovirales
Family: Coronaviridae
Genus: Coronavirus
Genome: (+)ssRNA, ~30kb (20-33kb)
Genes:
1a, 1b, S, E, M, N, Assrtd ORFs

Avian infectious bronchitis virus (IBV) is the prototype species of the genus Coronavirus. Other members include the respiratory coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, SARS-HCoV and HCoV-HKU1.

Other members of the family include bovine coronavirus (BCV), canine coronavirus (CCV), feline infectious peritonitis virus (FIPV), murine hepatitis virus (MHV), porcine epidemic diarrhoea virus (PEDV), porcine hemagglutinating encephalomyelitis virus (HEV), porcine transmissible gastroenteritis virus (TGEV), rat coronavirus (RCV), turkey coronavirus (TCV) and the rabbit coronavirus (RbCV).

The human coronavirus particle contains a positive sense, infectious, single-stranded RNA ([+]ssRNA) genome that is methylated at the 5' terminus and adenylated at the 3' terminus with a poly(A). The virus replicates in the host cells cytoplasm

Human cronavirus NL63 genome schematic

Figure 1.
Schematic representation of the human coronavirus NL63 (HCoV-NL63) [+]ssRNA genome. Based on GenBank accession no. NC_005831.

 

The coronaviruses are pleomorphic and range from 60 to 200nm in diameter with a filamentous nucleocapsid and an external studding of spiky projections giving the virions their "crown-like" appearance (crown translate to corona in Latin; Figure 2). The haemagglutinin-esterase (HE) protein is only present within the group II coronaviruses. Grouiungs were created based on antigenic reactivities, to further classify the coronaviruses.

The spike protein (S) plays a role in attachment to and fusion with the target cell, and is the major coronavirus antigen.

The membrane protein (M) spans the membrane, i.e. it is a transmembrane protein, becoming involved in the budding of coronavirus particles from the cell.

 

Genus coronavirus schematic
Figure 2.
Schematic representation of the human coronavirus virion.

 

HCoV are traditionally thought of as minor players in human respiratory disease (even the most recent vrirology texts still present this as fact). The most common quote is that of HCoV causing up to a third of all cases of the common cold, a self-limiting disease of the upper respiratory tract (URT). The recent resurgence in HCoV research brought about by the interest in the SARS-HCoV, has shed new light on to the role of these agents.

HCoV are now known to be present as the sole agent, in a number of infections clinically located in the lower respiratory tract (LRT). Such disease entities include bronchitis, bronchiolitis and pneumonia.

Older methods to detect HCoV infection include isolation of the virus by culture, visualisation of the virions using electron micrscopy (EM) and detection of past or current infection using serological techniques.

Isolaton by culture is difficult since the HCoV are fastidious, with most success occurring from the use of tissue and primary cells. Little has been done to further characterise the primary isolation of HCoV strains, and today the technique is largely used for the growth of the lab-adapted strains. In fact, the most recently described HCoV, HKU1 was reported without any concurrent isolation of infectious virus. WI38 and MRC5 cells have been used to islaote HCoV.

EM is not commonly used in todays high-throughput diagnostic laboratories, therefore its role in idntifying virus is limited tothe specialist public health or research laboratories.

Serology is still performed today but improved methods for expressing single gene products have led to the description of immun status even from the most recently described HCoV. Haemagglutination inhibition, neutralisation of infection ("neutralisation"), complemet fixation and ELISA have been most frequently reported.

Today's techniques are almost exclusivley based around the polymerase chain reaction (PCR). As more data accumulates from the use of this sensitive and specific tool, so the incidence of detection of HCoV infections is climbing, and more cases of the virus are being found in patients with LRT. Whether the virus infects these tissues directly, or causes an indirect cytokine storm as a result of its replication in the URT is still to be concluded.

No specific, targetted antiviral therapy or HCoV vaccines exist yet.