Human Coronavirus OC43 (HCoV-OC43) is one of the common pathogens responsible for the seasonal common cold in people worldwide. It belongs to the Betacoronavirus genus, placing it in the same broader category as the viruses that cause Severe Acute Respiratory Syndrome (SARS) and COVID-19. Recognized for its long-term presence in the human population, HCoV-OC43 is classified as a Group 2 coronavirus, subgroup Embecovirus.
Defining Human Coronavirus OC43
HCoV-OC43 is one of the four endemic human coronaviruses, alongside HCoV-229E, HCoV-NL63, and HCoV-HKU1, that circulate continuously among humans. These four viruses are responsible for a significant percentage of annual upper respiratory infections globally. OC43 and 229E alone contribute to an estimated 10% to 30% of all common colds, indicating OC43 has been successfully adapted to humans for decades.
Its mild severity contrasts sharply with highly pathogenic coronaviruses like SARS-CoV-2 and MERS-CoV, which emerged more recently and caused significant global public health crises. While those strains are characterized by high virulence and mortality, OC43 typically causes a self-limiting, mild upper respiratory illness. The virus infects all age groups and is prevalent globally, though its infection rate may peak every two or three years.
Anatomy and Replication Cycle
The HCoV-OC43 virion is an enveloped particle, roughly 120 to 160 nanometers in diameter, that encases a positive-sense, single-stranded RNA genome. This RNA genome is one of the largest among RNA viruses, spanning approximately 27 to 32 kilobases. The genome is capped and polyadenylated, allowing it to act directly as messenger RNA once inside a host cell. The viral structural components, including the characteristic spike (S), envelope (E), and membrane (M) proteins, are embedded in a lipid envelope derived from the host cell.
OC43 is unique among some coronaviruses in that it also possesses a shorter surface projection called the hemagglutinin-esterase (HE) protein, which is found in the Embecovirus subgenus. The primary mechanism for host cell entry begins with the spike (S) protein binding to a specific molecule on the human respiratory cell surface. This receptor is a sugar molecule known as N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2), which is expressed on ciliated cells in the respiratory tract.
Once inside, the viral RNA is released and translated into replicase polyproteins, which form the machinery for copying the genome and generating sub-genomic RNA. These sub-genomic RNAs serve as templates for the structural proteins (S, E, M, HE, and nucleocapsid (N)). The structural proteins are translated and moved to the endoplasmic reticulum–Golgi intermediate compartment (ERGIC). The newly synthesized RNA genomes are packaged by the N protein, and the resulting nucleocapsid buds into the ERGIC membrane, completing the assembly of new virions.
Symptoms and Seasonal Patterns
Infection with HCoV-OC43 typically presents as a mild upper respiratory tract illness, often indistinguishable from a common cold. The most frequent symptoms include a runny nose, cough, sore throat, headache, and a low-grade fever, with symptoms usually appearing within two to four days after exposure. The infection is generally self-limiting, resolving on its own within a few days without specific medical intervention.
While most cases are mild, the virus can occasionally cause more severe lower respiratory tract infections, such as bronchitis or pneumonia. This progression to a more serious illness is more common in vulnerable populations, including infants, the elderly, and individuals with weakened immune systems or underlying cardiopulmonary conditions. In rare instances, OC43 has been associated with neurological symptoms, manifesting as a viral encephalitis.
HCoV-OC43 exhibits a distinct seasonality, with infections peaking during the cooler months in temperate climates. This seasonal pattern is shared with the other endemic human coronaviruses, though the exact reasons for this winter peak are not fully understood. Environmental conditions or changes in human behavior during these months likely contribute to the increased transmission.
Tracing the Viral Origin
HCoV-OC43 is believed to have originated from an animal reservoir before making a cross-species jump to humans. Genetic and antigenic analysis strongly links HCoV-OC43 to bovine coronavirus (BCoV), a virus that infects cattle. The two viruses share a high degree of genetic similarity, with nucleotide identity between human and bovine strains in the range of 96% to 97%.
Molecular clock analysis suggests that the spillover event from cattle to humans occurred relatively recently in history. The estimated timeline for this cross-species jump is around the late 19th century, with several studies pointing to a date around 1890. This timing has led some researchers to speculate that the introduction of HCoV-OC43 might have been the cause of the 1889–1890 “Russian Flu” pandemic, which was historically attributed to influenza.