Title：Changes in ORF4 of HCoV-229E under different culture conditions.

Authors：Kitai Y, Kojima S, Aishajiang A, Kawase M, Watanabe O, Yabukami H, Hashimoto R, Akahori Y, Katoh H, Takayama K, Nishimura H, Shirato K, Takeda M.

Journal：J Gen Virol

Human coronavirus 229E (HCoV-229E) is one of the viruses that cause respiratory infections such as the common cold. Its genome contains a gene called ORF4, whose function is still not well understood. Previous studies have shown that when this virus is grown in commonly used laboratory cell lines, the ORF4 gene often becomes shortened due to mutations.

In this study, we found that viruses directly collected from patients with respiratory infections retained a complete ORF4 gene, which is 219 amino acids long. However, when those same viruses were grown in standard lab cells, the ORF4 gene frequently became truncated, resulting in shorter forms such as 168, 143, or even just 16 amino acids.

Interestingly, when the viruses were grown in airway cells that closely mimic the environment inside the human body, the full-length ORF4 gene remained intact and stable over a long period.

These findings suggest that ORF4 may play an important role during natural infections in humans. They also highlight the importance of using more physiologically relevant culture systems when studying the true characteristics of the virus.