human coronavirus OC43

Four HCoV-OC43 genotypes (A to D) have been identified, with genotype D most likely arising from genetic recombination. The complete genome sequencing of genotypes C and D and bootscan analysis shows recombination events between genotypes B and C in the generation of genotype D. Of 29 viral variants identified, none belong to the more ancient genotype A. Molecular clock analysis using spike and nucleocapsid genes dates the most recent common ancestor of all genotypes to the 1950s. Genotype B and C date to the 1980s. Genotype B to the 1990s, and genotype C to the late 1990s to early 2000s. The recombinant genotype D variants were detected as early as 2004. The genome is made of approximately 30,700 nucleotides and encodes for several structural proteins:

• Spike (S) Protein: Facilitates viral entry into host cells by binding to receptors.{{Citation |last1=Liu |first1=Ding X. |title=Human Coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae) |date=2021 |encyclopedia=Encyclopedia of Virology |pages=428–440 |publisher=Elsevier |language=en |doi=10.1016/B978-0-12-809633-8.21501-X |isbn=978-0-12-814516-6 |pmc=7204879 |last2=Liang |first2=Jia Q. |last3=Fung |first3=To S.}}
• Hemagglutinin-Esterase (HE) Protein: An additional shorter spike protein characteristic of embecoviruses, which binds to N-acetyl-9-O-acetylneuraminic acid receptors on host cells.
• Membrane (M) Protein: Plays a role in viral assembly and budding.
• Envelope (E) Protein: Involved in virus morphogenesis and release.
• Nucleocapsid (N) Protein: Encapsidates the viral RNA genome, forming the nucleocapsid structure.{{cite journal |last1=Chechetkin |first1=Vladimir R. |last2=Lobzin |first2=Vasily V. |title=Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution |journal=Journal of Biomolecular Structure and Dynamics |date=5 December 2022 |volume=40 |issue=21 |pages=11239–11263 |doi=10.1080/07391102.2021.1958061 |pmid=34338591 |arxiv=2106.07005 }}

Comparison of HCoV-OC43 with the most closely related strain of Betacoronavirus 1 species, bovine coronavirus BCoV, indicated that they had a most recent common ancestor in the late 19th century, with several methods yielding most probable dates around 1890, leding authors to speculate that an introduction of the former strain to the human population might have caused the 1889–1890 pandemic, which at the time was attributed to influenza. The COVID-19 pandemic brought further evidence of a link, as the 1889–1890 pandemic produced symptoms closer to those associated with COVID-19 (the infection caused by the SARS-CoV-2 betacoronavirus) than to influenza.{{Cite news|last=Knudsen|first=Jeppe Kyhne|date=13 August 2020|title=Overraskende opdagelse: Coronavirus har tidligere lagt verden ned|language=da|trans-title=Surprising discovery: Coronavirus has previously brought down the world|work=DR|url=https://www.dr.dk/nyheder/viden/kroppen/overraskende-opdagelse-coronavirus-har-tidligere-lagt-verden-ned|access-date=13 August 2020|quote=A presumed influenza pandemic in 1889 was actually caused by coronavirus, Danish research shows.}} Brüssow, in August 2021, referred to the evidence that OC43 caused the 1889–1890 outbreak as "indirect, albeit weak" and was "conjectural", yet the 1889 epidemic was the best historical record to make predictions about the current COVID-19 path due to the similar "clinical and epidemiological characteristics".{{cite journal |last1=Brüssow |first1=Harald |title=What we can learn from the dynamics of the 1889 'Russian flu' pandemic for the future trajectory of COVID-19 |journal=Microbial Biotechnology |date=2021 |volume=14 |issue=6 |pages=2244–2253 |doi=10.1111/1751-7915.13916 |pmid=34464023 |pmc=8601188 }}

The origin of HCoV-OC43 is uncertain, but it is thought that it may have originated in rodents, then passed through cattle as intermediate hosts.{{cite journal |last1=Forni |first1=Diego |last2=Cagliani |first2=Rachele |last3=Clerici |first3=Mario |last4=Sironi |first4=Manuela |title=Molecular Evolution of Human Coronavirus Genomes |journal=Trends in Microbiology |date=January 2017 |volume=25 |issue=1 |pages=35–48 |doi=10.1016/j.tim.2016.09.001 |pmid=27743750 |pmc=7111218 |doi-access=free }} A deletion from BCoV to HCoV-OC43 may have taken place for the interspecies transmission event from bovines to humans.

Human coronavirus OC43 (HCoV-OC43) is commonly associated with mild upper respiratory tract infections, presenting symptoms such as nasal congestion, sore throat, cough, and fever. Certain populations, particularly infants, the elderly and immunocompromised individuals, may experience more severe lower respiratory tract infections, including bronchitis and pneumonia.{{cite journal |last1=Zeng |first1=Zhi-Qi |last2=Chen |first2=De-Hui |last3=Tan |first3=Wei-Ping |last4=Qiu |first4=Shu-Yan |last5=Xu |first5=Duo |last6=Liang |first6=Huan-Xi |last7=Chen |first7=Mei-Xin |last8=Li |first8=Xiao |last9=Lin |first9=Zheng-Shi |last10=Liu |first10=Wen-Kuan |last11=Zhou |first11=Rong |title=Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China |journal=European Journal of Clinical Microbiology & Infectious Diseases |date=February 2018 |volume=37 |issue=2 |pages=363–369 |doi=10.1007/s10096-017-3144-z |pmc=5780525 |pmid=29214503 }}

A summary of the signs and symptoms include:

• Nasal Congestion: A blocked or runny nose is a frequent symptom. [22]
• Sore Throat: Discomfort or irritation in the throat often accompanies the infection. [22]
• Cough: A persistent cough is commonly observed. [22]
• Fever: Elevated body temperature may occur in some cases.[22]
• Headache: Some individuals report headaches during the course of the infection.

While primarily targeting the respiratory system, HCoV-OC43 has also been implicated in rare cases of central nervous system involvement. There have been reports linking HCoV-OC43 to fatal encephalitis in infants with underlying health conditions.{{cite journal |last1=Kasereka |first1=Masumbuko C. |last2=Hawkes |first2=Michael T. |title=Neuroinvasive potential of human coronavirus OC43: case report of fatal encephalitis in an immunocompromised host |journal=Journal of NeuroVirology |date=April 2021 |volume=27 |issue=2 |pages=340–344 |doi=10.1007/s13365-020-00926-0 |pmc=7786874 |pmid=33405204 }} Outbreaks of HCoV-OC43 have occurred in long-term care facilities during the COVID-19 pandemic. Clinical features of those affected were described similar to those of SARS-CoV-2 infection.{{cite journal |last1=Ohyama |first1=Koji |last2=Honda |first2=Hitoshi |last3=Aoki |first3=Momoko |last4=Wakuda |first4=Mitsutaka |last5=Kitahara |first5=Tomoaki |last6=Kaede |first6=Chisaki |last7=Doi |first7=Yohei |last8=Uehara |first8=Yuki |title=Resurgence of human coronavirus OC43 at a long-term care facility during the coronavirus disease 2019 (COVID-19) pandemic: Outbreak investigation |journal=Antimicrobial Stewardship & Healthcare Epidemiology |date=2023 |volume=3 |issue=1 |pages=e97 |doi=10.1017/ash.2023.172 |pmid=37325679 |pmc=10265732 }}

Along with HCoV-229E, a species in the genus Alphacoronavirus, HCoV-OC43 is among the viruses that cause the common cold. Both viruses can cause severe lower respiratory tract infections, including pneumonia, in infants, the elderly, and immunocompromised individuals such as those undergoing chemotherapy and those with HIV/AIDS.{{cite journal |doi=10.1016/j.cll.2009.07.007 |title=Recently Discovered Human Coronaviruses |year=2009 |last1=Wevers |first1=Brigitte A. |last2=Van Der Hoek |first2=Lia |journal=Clinics in Laboratory Medicine |volume=29 |issue=4 |pages=715–724 |pmid=19892230|pmc=7131583 |doi-access=free }}{{cite book |last1=Mahony |first1=James B. |year=2007 |chapter=Coronaviruses |editor1-first=Patrick R. |editor1-last=Murray |editor2-first=Ellen Jo |editor2-last=Baron |editor3-first=James H. |editor3-last=Jorgensen |editor4-first=Marie Louise |editor4-last=Landry |editor5-first=Michael A. |editor5-last=Pfaller |title=Manual of Clinical Microbiology |edition=9th |pages=1414–23 |location=Washington D.C. |publisher=ASM Press |isbn=978-1-55581-371-0}}{{cite journal |doi=10.2174/187152607780090757 |title=Antiviral Strategies Against Human Coronaviruses |year=2007 |last1=Pyrc |first1=K. |last2=Berkhout |first2=B. |last3=Van Der Hoek |first3=L. |journal=Infectious Disorders Drug Targets |volume=7 |pages=59–66 |pmid=17346212 |issue=1}} Rare cases with central nervous system involvement have been reported, usually manifesting as viral encephalitis.{{cite journal |last1=Forni |first1=Diego |last2=Cagliani |first2=Rachele |last3=Arrigoni |first3=Federica |last4=Benvenuti |first4=Martino |last5=Mozzi |first5=Alessandra |last6=Pozzoli |first6=Uberto |last7=Clerici |first7=Mario |last8=De Gioia |first8=Luca |last9=Sironi |first9=Manuela |title=Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host |journal=Virus Evolution |date=16 December 2021 |volume=7 |issue=2 |pages=veab061 |doi=10.1093/ve/veab061 |pmid=34527284 |pmc=8344746 }}

HCoV-OC43 facilitates entry by attaching to host cell receptors through spike (S) proteins. Once inside the cell, the virus releases positive-sense single-stranded RNA genome, which is translated and replicated using the host's cellular machinery. Recent studies have employed ribosome profiling and RNA sequencing to analyze the transcriptional and translational landscape of HCoV-OC43 infection. This has uncovered unexpected features in the viral genome, including short open reading frames upstream of major genes and an alternative translation start site within the M gene.{{cite journal |last1=Bresson |first1=Stefan |last2=Sani |first2=Emanuela |last3=Armatowska |first3=Alicja |last4=Dixon |first4=Charles |last5=Tollervey |first5=David |title=The transcriptional and translational landscape of HCoV-OC43 infection |journal=PLOS Pathogens |date=27 January 2025 |volume=21 |issue=1 |pages=e1012831 |doi=10.1371/journal.ppat.1012831 |doi-access=free |pmc=11771880 |pmid=39869630 }}

Once infected, the host cells mount an immune response to counteract the effect of the virus. HCoV-OC43 infection has been shown to remodel gap junction-mediated intercellular communication, specifically affecting Connexin 43 (Cx43), which may influence the spread of the virus and the host's immune response.{{Cite journal |last1=Karmakar |first1=Souvik |last2=Das Sarma |first2=Jayasri |date=2024-05-31 |title=Human coronavirus OC43 infection remodels connexin 43-mediated gap junction intercellular communication in vitro |journal=Journal of Virology |volume=98 |issue=7 |pages=e00478–24 |doi=10.1128/jvi.00478-24 |pmc=11264776 |pmid=38819132 }} Envelope (E) proteins play a key role in viral assembly, morphogenesis and pathogenesis. Protein-protein interactions and homo-oligomeric ion channel formation through E protein interactions are essential for virion morphology and the host cell's response to infection.{{cite journal |last1=Stodola |first1=Jenny K. |last2=Dubois |first2=Guillaume |last3=Le Coupanec |first3=Alain |last4=Desforges |first4=Marc |last5=Talbot |first5=Pierre J. |title=The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology |journal=Virology |date=February 2018 |volume=515 |pages=134–149 |doi=10.1016/j.virol.2017.12.023 |pmid=29287230 |pmc=7118982 }}

If HCoV-OC43 was indeed the pathogen responsible for the 1889–1890 pandemic, which resembled the COVID-19 pandemic, severe disease was much more common and mortality much higher in populations that had not previously been exposed.{{cite journal |last1=Brüssow |first1=Harald |last2=Brüssow |first2=Lütz |title=Clinical evidence that the pandemic from 1889 to 1891 commonly called the Russian flu might have been an earlier coronavirus pandemic |journal=Microbial Biotechnology |date=13 July 2021 |volume=14 |issue=5 |pages=1860–1870 |doi=10.1111/1751-7915.13889 |pmid=34254725 |pmc=8441924 }}

Coronaviruses have a worldwide distribution, causing 10–15% of common cold cases (the virus most commonly implicated in the common cold is a rhinovirus, found in 30–50% of cases). Infections show a seasonal pattern with most cases occurring in the winter months in temperate climates, and summer and spring in warm climates.{{cite journal |pmid=17944272 |year=2007 |last1=Van Der Hoek |first1=L |title=Human coronaviruses: What do they cause? |volume=12 |issue=4 Pt B |pages=651–8 |journal=Antiviral Therapy |doi=10.1177/135965350701200S01.1 |s2cid=31867379 |doi-access=free }}{{cite journal |doi=10.1016/j.ejim.2004.01.006 |title=The common cold: A review of the literature |year=2004 |last1=Wat |first1=Dennis |journal=European Journal of Internal Medicine |volume=15 |issue=2 |pages=79–88 |pmid=15172021|pmc=7125703 }}{{cite journal |doi=10.1126/science.abb5793 |title=Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period |last1=Kissler |first1=Stephen M. |journal=Science |date=April 14, 2020|volume=368 |issue=6493 |pages=860–868 |pmid=32291278 |pmc=7164482 |bibcode=2020Sci...368..860K |doi-access=free }}{{cite journal |pmid=25757061|year=2015 |last1=Berry | first1=Michael |journal=Viruses |title= Identification of New Respiratory Viruses in the New Millennium|volume=7 |issue=3 |pages=996–1019 |doi=10.3390/v7030996 |pmc=4379558 |doi-access=free }} As OC43 is capable of infecting porcine tissues,{{cite journal | vauthors = Xu G, Qiao Z, Schraauwen R, Avan A, Peppelenbosch MP, Bijvelds MJ, Jiang S, Li P | title = Evidence for cross-species transmission of human coronavirus OC43 through bioinformatics and modeling infections in porcine intestinal organoids. | journal = Veterinary Microbiology | volume = 293 | pages = 110101 | date = April 2024 | pmid = 38718529 | doi = 10.1016/j.vetmic.2024.110101| doi-access = free}} it is likely that pigs serve as a zoonotic reservoir for this disease, reinfecting the human population.

• Human coronavirus HKU1

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{{Wikispecies}}

• [http://virology-online.com/viruses/CORZA4.htm Virology online]
• [https://web.archive.org/web/20070309144307/http://www-micro.msb.le.ac.uk/3035/Coronaviruses.html Coronaviruses]
• [http://viralzone.expasy.org/all_by_species/764.html Viralzone: Betacoronavirus]
• [http://www.viprbrc.org/brc/home.do?decorator=corona Virus Pathogen Database and Analysis Resource (ViPR): Coronaviridae]

{{Human coronaviruses}}

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Category:Betacoronaviruses

Category:Viral respiratory tract infections

Category:Infraspecific virus taxa

Category:1889–1890 flu pandemic