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PubMed1978

Seroepidemiologic study of human coronavirus OC43 infections in Italy.

Human Coronavirus OC43 from suckling mouse brain (SMB) suspension has been adapted to grow in human embryonic lung fibroblast cell cultures. Complement-fixing and hemagglutinating antigens were prepared from infected cell cultures and used in parallel with the same antigens from SMB for a study of the prevalence of OC43 antibody in Northern Italy as well as for the serodiagnosis of recent OC43 infections and reinfections. Results show (i) a higher sensitivity of the hemagglutination-inhibition as compared to the complement fixation test both for antibody detection in seroepidemiological studies and serodiagnosis of acute infections, (ii) a high prevalence of OC43 antibody in Northern Italy, so that only exceptionally are people older than 12 years seronegative, (iii) a high rate of OC43 reinfections during the winter-spring season 1976/77 in a population sample with preexisting antibody (iv) a good quality of reagents prepared from cell cultures, and hence free of contaminating mouse viruses, such as mouse hepatitis virus.

Adolescent↗
PubMed1977

Antibodies to human coronavirus OC43 measured by radial haemolysis in gel.

An application of the haemolysis-in-gel (HIG) technique was developed to quantitate antibodies against the human coronavirus OC43. Preinfection and convalescent sera from two patients with verified OC43 infection showed a significant increase in antibody titres measured by HIG as well as by haemagglutination-inhibition (HI). 241 of the other 306 sera tested (80%) caused radial haemolysis in gels containing viral antigen-sensitized erythrocytes and complement. No haemolysis was seen in gels prepared with unifected material. Correlation of the diameter of the haemolysis ring to the respective HI titre was highly significant. However, 62 sera (20%) with HI titres between 8 and 320 were negative in the HIG. Attempts to show that these sera contained nonspecific inhibitors of haemagglutination were unsuccessful. OC43 HI and HIG probably measure different antibody ppulations.

Antibodies, Viral↗
PubMed1978

Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera.

Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay.

Antiviral Agents↗
PubMed1979

OC43 strain-related coronavirus antibodies in different age groups.

Serum antibodies against human coronavirus OC43 in different age groups were measured by complement fixation (CF), haemagglutination inhibition (HI), radial diffusion haemolysis-in-gel (HIG), and solid-phase radioimmunoassay (RIA) methods. Antigen grown in suckling mouse brain was used in all tests. Results obtained by the CF and HIG tests, and the RIA, were in good agreement with regard to the presence or absence of antibodies. Similar results were also obtained with the HI test if nonspecific haemagglutination inhibitors were first removed by treatment with phospholipase C and only titers of 1:20 or greater were considered positive. Children 6--23 months of age (n = 45) were without measurable coronavirus antibodies in all four assays. A rapid increase in the prevalence of antibodies then occurred in subsequent age groups, and practically all persons 6 years of age or older were found to have OC43 antibodies as measured by the HIG test or the RIA. The mean antibody levels determined by these two methods continued to increase, however, up to the age group of 10--14 years. This increase in antibody levels after the initial antibody incidence plateau may be due to boosting effects caused by related coronavirus strains, since OC43 antigens are known to cross-react with antibodies induced by other human coronaviruses. Taken together, these data suggest that OC43 virus, or an antigenically related coronavirus strain, is very common in Finland.

Adolescent↗
PubMed2026

Spatiotemporal dynamics and phylogeography of HCoV-NL63 and HCoV-OC43 in Thailand, 2024-2025.

Endemic human coronaviruses (HCoVs) HCoV-NL63 and HCoV-OC43 are common causes of acute respiratory infections (ARI), yet integrated surveillance and genomic data from Southeast Asia remain limited. We characterized HCoV-NL63 and HCoV-OC43 circulation in Thailand, during 2024-2025 using routine real-time RT-PCR testing, partial spike sequencing, and time-scaled phylogenetic analyses with global references. Among 11,709 ARI specimens, 329/8,122 were HCoV-positive in 2024 (4.05%) and 131/3,587 in 2025 (3.65%). Positivity was strongly seasonal, peaking in winter, and SARS-CoV-2 surges in the same testing stream generally coincided with lower endemic HCoV positivity. Genotype composition differed by virus: HCoV-OC43 was dominated by genotypes K and J at near-equal frequencies (48.3% and 47.2%), whereas HCoV-NL63 was mainly genotype C4 (43.6%), followed by B2 (32.7%) and C3 (20.9%). Time-scaled phylogenies placed Thai sequences across multiple regions of global diversity, consistent with repeated introductions and onward transmission within several co-circulating lineages. Estimated substitution rates were 3.86 × 10-4 substitutions/site/year for HCoV-NL63 and 9.27 × 10-4 for HCoV-OC43. Discrete-trait phylogeography supported bidirectional connectivity involving Thailand, with virus-specific differences in the most supported routes. Skygrid reconstructions suggested declines in genetic diversity after 2020, overlapping the COVID-19 era, with a more pronounced decrease for HCoV-OC43. Evidence for selection was limited and inconsistent for HCoV-NL63, whereas several HCoV-OC43 sites overlapped codon-based signals of diversifying selection. Overall, these findings provide a baseline for endemic HCoV seasonality, genotype composition, and connectivity in Thailand, and support continued genomic surveillance in Southeast Asia.

Thailand↗
PubMed2025

The transcriptional and translational landscape of HCoV-OC43 infection.

The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of the common cold. Here, we generated a high-resolution atlas of the transcriptional and translational landscape of OC43 during a time course following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified previously unannotated ORFs. These included several potential short upstream ORFs and a putative ORF nested inside the M gene. In parallel, we analyzed the cellular response to infection. Endoplasmic reticulum (ER) stress response genes were transcriptionally and translationally induced beginning 12 and 18 hours post infection, respectively. By contrast, conventional antiviral genes mostly remained quiescent. At the same time points, we observed accumulation and increased translation of noncoding transcripts normally targeted by nonsense mediated decay (NMD), suggesting NMD is suppressed during the course of infection. This work provides resources for deeper understanding of OC43 gene expression and the cellular responses during infection.

Humans↗
PubMed1979

Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.

A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.

Animals↗
PubMed1978

Antigenic relationship of the feline infectious peritonitis virus to coronaviruses of other species.

Utilizing the direct and indirect fluorescent antibody procedure, the antigenic relationship of the feline infectious peritonitis virus (FIPV) to 7 other human and animal coronaviruses was studied. FIPV was found to be closely related to transmissible gastroenteritis virus (TGEV) of swine. Transmissible gastroenteritis virus and FIPV were in turn antigenically related to human coronavirus 229E (HCV-229E) and canine coronavirus (CCV). An interesting finding in the study was that the 8 coronaviruses selected for this study fell into one of two antigenically distinct groups. Viruses in each group were antigenically related to each other to varying degrees, but were antigenically unrelated to coronaviruses of the second group. The first antigenically related group was comprised of mouse hepatitis virus, type 3 (MHV-3), hemeagglutinating encephalomyelitis virus 67N (HEV-67N) of swine, calf diarrhea coronavirus (CDCV), and human coronavirus 0C43 (HCV-OC43). The second antigenically related group was comprised of FIPV, TGEV, HCV-229E and CCV.

Antigens, Viral↗
PubMed1978

Diagnosis of human coronavirus infection by immunofluorescence: method and application to respiratory disease in hospitalized children.

Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.

Adult↗
PubMed1979

Plaque assay and improved yield of human coronaviruses in a human rhabdomyosarcoma cell line.

Propagation and plaque assay of human coronavirus prototypes were studied in two human cell lines: a diploid fetal tonsil (FT) and a heteroploid rhabdomyosarcoma (RD) cell lines. Plaques, observed within 2 to 3 days on FT cell monolayers with both 229E and OC43 viruses, appeared as colorless areas after staining with neutral red or crystal violet, whereas neutral red staining was required for visualization of plaques on RD cells. The plating efficiencies were approximately equal between the two cell lines, but virus assay by plaque formation was 15- to 30-fold more efficient than tube dilution assay with 50% endpoints. The discrepancy between 50% endpoint and plaque-forming unit values was striking and appeared to result from the fact that killing of cells (particularly RD cells) by coronaviruses was not accompanied by visible changes in the cells but killing was detected by the failure of infected cells to stain with a vital dye. The latent phase in one-step growth curves was 5 to 6 h for both viruses in either cell line, but the maximum yield of intracellular virus was reached in 18 to 20 h for FT cells and 24 to 28 h for RD cells. Virus release also differed between the two cell lines: in FT cells, the maximum yield of extracellular virus was reached 2 to 3 h later than that of intracellular virus, whereas in RD cells, the difference was 5 h for 229E virus and 10 h for OC43 virus. Although both cell lines appear equally useful for plaque assay, RD cells would be preferred for mass virus propagation because yields (5 X 10(8) plaque-forming units per ml) were 10-fold higher than in FT cells, a finding true for both virus prototypes.

Cell Line↗
PubMed2025

Global siRNA screen identifies human host factors critical for SARS-CoV-2 replication and late stages of infection.

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, most of these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased toward the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published functional screens and proteomics data to reveal (i) common pathways that were identified in all OMICs datasets-including regulation of Wnt signaling and gap junctions, (ii) pathways uniquely identified in this screen-including NADH oxidation, or (iii) pathways supported by this screen and proteomics data but not published functional screens-including arachionate production and MAPK signaling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 32 proteins that were determined to impact viral replication and 27 impacting late stages of infection, respectively. Additionally, a subset of proteins was tested across other coronaviruses revealing a subset of proviral factors that were conserved across pandemic SARS-CoV-2, epidemic SARS-CoV-1 and MERS-CoV, and the seasonal coronavirus OC43-CoV. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo. These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals.

Humans↗
PubMed1978

Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis.

The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.

Adult↗
PubMed1975

The Tecumseh study of respiratory illness. VIII. Acute infection in chronic respiratory disease and comparison groups.

Individuals with chronic lung disease and their families were selected from the Tecumsch community along with similarly selected families as comparison groups and studied for 1-year periods. Occurence of acute respiratory illness was ascertained weekly by telephone and calculated as an annual rate. Persons with chronic bronchitis not only experienced more acute lower respiratory illness than healthy comparison subjects, but total illness rates were somewhat higher as well. Infection rates were determined from blood samples taken 3 times from each participant during the surveillance year. Antibody tests were performed for respiratory syncytial virus, para-influenza virus types 1, 2, and 3, influenza types A and B, coronavirus OC43, Mycoplasma pneumoniae, and Haemophilus influenzae. Differences in serologic infection rates among the subgroups of the population were similar to those seen in the clinical data, with more frequent infection among those with bronchitis than among the comparison subjects. This finding indicates that some degree of increased susceptibility to actual infection existed among those individuals with bronchitis. Influence of smoking on illness and infection rates was also examined. Infections were, in general, more frequent in smokers than in nonsmokers, but illness rates were reversed, suggesting that perception of disease differed in the 2 groups. Rates of illness and infection of other adults in the families of the index individuals with bronchitis were not influenced by the higher rates seen in the index individuals; however, it was of interest that children of persons with bronchitis did have somewhat higher rates of infection than children of comparison subjects.

Acute Disease↗