In a previous posting, it was related how, in 1965, David Tyrrell, at the Common Cold Unit in Salisbury, England, grew a virus from a schoolboy with a cold (1). That virus, designated B814, would be the first known human coronavirus. With the aid of Swedish surgeon Bertil Hoorn, B814 was grown in human trachea organ cultures that were inoculated with throat swabs taken from the sick boy. The main point of the previous posting was that the detection of B814 depended on the exceptional electron microscopy skills of June Almeida. In addition, Almeida noted that the morphology of B814 resembled that of the previously isolated infectious bronchitis virus (IBV) of chickens. She then concluded that B814 and IBV are members of a previously unclassified family of viruses. Then, based on Almeida’s interpretation of B814’s morphology, she, Tyrrell, and Tony Waterson (a colleague of Tyrrell who recommended that Almeida be recruited to Tyrrell’s team), dubbed the new family “coronaviruses.”
Even though B814 is recognized as the first known human coronavirus, listings of coronaviruses that infect humans, as compiled in medical virology books and in the journal literature, generally include only seven coronaviruses, none of which has been shown to be identical to B814. These seven coronaviruses include four human coronaviruses that cause common colds (HCoVs 229E, NL63, OC43, and HKUI), and three animal coronaviruses that recently emerged in, and are highly virulent in humans (SARS, MERS, and SARS-CoV2). Where then does B814 fit in this compilation of coronaviruses? In search of an answer, here is a brief history of the discoveries of the human coronaviruses.
In 1966, at about the same time that Almeida was carrying out her electron microscopy analysis of B814, Dorothy Hamre and John Procknow, at the University of Chicago, recovered 5 viral isolates from medical students with colds (2). One of these isolates, 229E, was examined by Almeida, who found its morphology to be identical to that of B814. Then, in 1967, Robert Chanock and coworkers at the NIH used the organ culture technique to isolate yet other strains, including OC43, whose morphology likewise resembled that of B814 (3).
229E and OC43 were virtually the only HCoVs being studied during the next thirty years, mainly because they were the easiest of the HCoV strains to work with. As for B814, it could only be grown in organ culture (1). In contrast, clinical samples of 229E could be grown directly in cell culture. And while OC43 was originally grown in organ culture, it was subsequently adapted to growth in suckling mouse brain, and then to growth in cell culture.
Both 229E and OC43 are clinically significant, as each caused multiple epidemics in the United States, at intervals of 2 to 3 years. Moreover, reinfection with each of these strains was common (4); a point that may be relevant to the current COVID-19 pandemic. In any case, in 1970 it was reported that B814 is not serologically identical to either OC43 or 229E (5). Little else seems to be known about B814.
The winter of 2002-2003 saw the emergence of the SARS coronavirus; a virus far more lethal in humans than either 229E or OC43. By the end of the SARS outbreak, a total of 8,096 cases were reported, of which 744 were fatal, for a fatality rate of about 12%. Prior to the SARS outbreak, coronavirus infections were regarded as merely mild nuisances. But the SARS outbreak led to an awareness that animal coronaviruses could represent a significant health threat to humans.
But yet other relatively mild HCoVs remained to be discovered. In 2004, researchers at the Erasmus Medical Center in the Netherlands isolated NL63 from a 7-month-old girl with coryza, conjunctivitis, fever, and bronchiolitis (6). The same year, another group of investigators in the Netherlands isolated a coronavirus, designated NL, from an 8-month-old boy with pneumonia (7). And, in 2004, researchers in New Haven, Connecticut, used a PCR-based approach to isolate a virus, designated the New Haven coronavirus (HCoV-NH), from young children with respiratory disease, (8).
NL63, NL, and NH are so-called group I coronaviruses. They are closely related to each other and may very well be the same species. In any case, these viruses are believed to be a significant cause of respiratory tract disease in infants and children. And, like SARS-CoV2, HCoV-NH has been associated with Kowasaki disease in children (9).
In 2005, researchers at the University of Hong Kong used RT-PCR to recover a novel human coronavirus from a sample taken earlier from a 71-year old man who presented in Hong Kong with a fever and a cold (10). HKU1 is a so-called group II coronavirus. As such, it is distinct from OC43, the only other known group II human coronavirus. [229E is a group I coronavirus. Sequence analysis shows SARS to be sufficiently different from any of the known human and animal coronaviruses for it to occupy a separate group.] It is not known whether B814, or any of the other uncharacterized HCoV strains from the 1960s (i.e., those strains that were grown only in organ culture) are similar or identical to the more recently isolated HCoVs.
MERS-CoV is the second deadly coronavirus to emerge in humans. It was first isolated from a patient in Saudi Arabia in 2012. It caused fewer than 2,500 confirmed cases worldwide. Yet it killed an astounding 35% of people with confirmed diagnoses. At present, we are in what is still the early phase of the SARS-CoV-2 (COVID-19) pandemic. SARS-CoV-2 is clearly far more transmissible than either SARS or MERS. Its fatality rate is not known but estimates are at about 1%. In any case, the above compendium hopefully includes all the coronavirus strains known to infect humans.
References:
- Norkin, L.C. June Almeida and the Discovery of the First Human Coronavirus, Posted on the blog June 2, 2020.
- Hamre, D., and J.J. Procknow, 1966. A new virus isolated from the human respiratory tract. Soc. Exp. Biol. Med. 121:190–193.
- McIntosh, K., J.H. Dees, W.B. Becker, A.Z. Kapikian, and R.M. Chanock, 1967. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Natl. Acad. Sci. USA. 57:933–940.
- Callow, K.A., H.F. Parry, M. Sergeant, and D.A. Tyrrell, 1990. The time course of the immune response to experimental coronavirus infection of man. Infect. 105:435–446.
- Bradburne, A.F., 1970. Antigenic relationships amongst coronaviruses. Gesamte Virusforsch. 31:352–364.
- van der Hoek, L., K. Pyrc, M.F, Jebbink, et al., 2004, Identification of a new human coronavirus. Med. 10:368–373.
- Fouchier, R.A., N.G. Hartwig, T.M. Bestebroer, et al., 2004. A previously undescribed coronavirus associated with respiratory disease in humans. Natl. Acad. Sci. USA. 101:6212–6216.
- Esper, F., R.A. Martinello, R.P. Boucher, et al., 2005. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children. Infect. Dis. 191:492–498.
- Esper, F., E.D. Shapiro, C. Weibel, D. Ferguson, M.L. Landry, and J.S. Kahn, 2005. Association between a novel human coronavirus and Kawasaki disease. Infect. Dis. 191:499–502.
- Woo, P.C., S.K. Lau, C.M. Chu, et al., 2005. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. Virol. 79:884–895.
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