Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion

Abstract

The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.

The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis

“…Mice were maintained at the Animal Care Facility of the Chinese Academy of Sciences. Groups of 10-day-old mice were intranasally inoculated with 5 l of the HCoV-OC43-WT or HCoV-OC43-⌬ns12.9 viral stock (32). The infected mice were monitored daily for weight loss and survival.…”

Oligomerization of the carboxyl terminal domain of the human coronavirus 229E nucleocapsid protein

“…Although HCoV-229E infections are generally mild, more severe upper and lower respiratory tract infections, such as bronchiolitis and pneumonia, have been well documented, particularly in infants, elderly individuals, and immunocompromised patients [1,3,4]. There have also been reports that clusters of HCoV-229E infections cause pneumonia in otherwise healthy adults [2,5].…”

“…Human coronavirus 229E (HCoV-229E), belonging to the alphacoronaviruses, was first identified in the 1960s and has generally been associated with symptoms of the common cold [1,2]. Although HCoV-229E infections are generally mild, more severe upper and lower respiratory tract infections, such as bronchiolitis and pneumonia, have been well documented, particularly in infants, elderly individuals, and immunocompromised patients [1,3,4].…”

“…The viral genome of coronaviruses consists of positive-sense, single-stranded RNA of approximately 30 kb, and it contains several genes encoding several structural and non-structural proteins that are required for progeny virion production [1]. The virion envelope surrounding the nucleocapsid contains the following structural proteins: S (spike) protein, M (membrane), E (envelope), and N (nucleocapsid).…”

Synthesis and inhibitory activity of sialic acid derivatives targeted at viral sialate-O-acetylesterases

“…HCoVs account for 10e30% of respiratory infections, in particular, the common cold, but they can also cause gastroenteritis and neurological disorders [12,13]. The infections are usually mild and subclinical, but strains related to OC43 and HKU1 were associated with severe human disease [14,15].…”