Biology subjects

Suryadinata, R.

Publications and source records attributed to Suryadinata, R..

3 recordsLinked to original sources

bioRxiv2026

Viral replication and host response in airway epithelial cells predicts coronavirus pathogenicity and identifies HCoV-229E as an atypical seasonal coronavirus

Human coronaviruses (HCoVs) range from mild seasonal strains to pathogenic viruses that cause severe pneumonia. The virological and host determinants that distinguish pathogenic coronaviruses (MERS-CoV, SARS-CoV-2) from seasonal strains (HCoV-229E, HCoV-NL63 and HCoV-OC43) remain poorly defined. To identify determinants of pathogenicity, we systematically compared replication, cellular tropism, innate responses and cytopathogenicity of pathogenic compared with seasonal HCoVs across nasal, bronchial, small airway and embryonic stem cell derived alveolar type II (AT2) epithelial cell cultures. All HCoVs preferentially infected ciliated cells in the upper airway, but only pathogenic viruses replicated to high titres in AT2 cells. Pathogenic HCoVs reprogrammed AT2 function and suppressed key innate immune signatures, consistent with distal lung epithelial dysfunction. In contrast, seasonal HCoVs were associated with limited alveolar replication and milder disruption of AT2 homeostasis. Strikingly, despite modest replication in all cell types, HCoV-229E induced pronounced epithelial injury, cilia loss and strong interferon stimulated gene expression, as well as induction of cellular stress/death programmes resembling those induced by MERS-CoV. These findings highlight the striking differences in cellular responses throughout the airways and between distinct HCoV strains and emphasizes the importance of assessing distal lung tropism and epithelial host responses to evaluate emergent coronaviruses to inform pandemic preparedness strategies.

microbiology↗

bioRxiv2026

Epistasis facilitates the long-term antigenic evolution of the influenza B virus hemagglutinin

The antigenic drift of viral glycoproteins must be balanced by purifying selection pressure to maintain functionality. Understanding these evolutionary processes is key to predicting and combating viral evolution but is primarily based on influenza A(H3N2), which may limit generalisability. By characterising the influenza B virus haemagglutinin (HA) over 8 decades of circulation in humans, we found continuous genetic diversification, punctuated with antigenic changes that did not follow a linear path in antigenic space. Antigenic change is primarily underpinned by re-occurring mutations and deletions at positions 136, 150, 162-165, 197 and 203. These residues form complex epistatic networks that modulate the antigenic impact of mutation recycling. They also generate permissive backbones on which immune escape can emerge with limited replicative fitness cost. Our study identifies critical similarities and differences with A(H3N2) evolution and demonstrates the role of epistasis in balancing antigenic novelty with viral fitness. Our findings and genetic, antigenic and phenotypic datasets support the development of genotype-to-phenotype prediction tools, but such predictions need to capture the complex outcomes of epistasis.

microbiology↗

bioRxiv2025

Contemporary seasonal human coronaviruses display differences in cellular tropism compared to laboratory-adapted reference strains

Seasonal human coronaviruses (sHCoVs) cause 15-30% of common colds. The reference strains used for research were isolated decades ago and have been passaged extensively but contemporary sHCoVs have been challenging to study as they are notoriously difficult to grow in standard immortalized cell lines. Here we addressed these issues by utilizing primary human nasal epithelial cells (HNECs) and immortalized human bronchial epithelial cells (BCi) differentiated at an air-liquid interface, as well as human embryonic stem cell-derived alveolar type II (AT2) cells to recover contemporary sHCoVs from human nasopharyngeal specimens. From 21 specimens we recovered four 229E, three NL63 and eight OC43 viruses. All contemporary sHCoVs showed sequence differences from lab-adapted CoVs, particularly within the spike gene. Evidence of nucleotide changes in the receptor binding domains within 229E and detection of recombination for both 229E and OC43 isolates was also observed. Importantly, we developed methods for the amplification of high titre stocks of NL63 and 229E, that maintained sequence identity, and we established methods for the titration of contemporary sHCoV isolates. Comparison of lab-adapted and contemporary strains in immortalised cell lines and airway epithelial cells revealed differences in cell tropism, growth kinetics and cytokine production between lab-adapted and contemporary sHCoV strains. These data confirm that contemporary sHCoVs differ from lab-adapted reference strains and, using the methods established here, should be used for study of CoV biology and evaluation of medical countermeasures. ImportanceZoonotic coronaviruses have caused significant public health emergencies. The occurrence of a similar spillover event in the future is likely and efforts to further understand coronavirus biology should be a high priority. Several seasonal coronaviruses circulate within the human population. Efforts to study these viruses have been limited to reference strains isolated decades ago due to the difficulty in isolating clinical isolates. Here, we use human airway and alveolar epithelial cultures to recover contemporary isolates of NL63, 229E and OC43. We establish methods to make high titre stocks and titrate 229E and NL63 isolates. We show that contemporary isolates of NL63 and OC43 have a different tropism within the respiratory epithelium compared to lab-adapted strains. Although 229E clinical and lab-adapted strains similarly infect the respiratory epithelium, differences in host response and replication kinetics are observed. Using the methods developed here, future research should include contemporary isolates when studying coronavirus biology.

microbiology↗