A groundbreaking discovery in virology has revealed the presence of hidden viral proteins within the genomes of certain single-stranded RNA (+ssRNA) viruses. This finding challenges long-held beliefs about the genetic makeup of these viruses and has significant implications for animal and plant viruses, including SARS-CoV-2 responsible for COVID-19.
Previously, some scientists dismissed the existence of these viral peptides as translation mishaps and replication errors. However, Thailand Medical News has been warning about these viral peptides and their potential pathogenicity. There is even speculation that some of these viral peptides may contribute to Long COVID, persisting after viral clearance.
Recent studies have confirmed the presence of viral peptides encoded by the SARS-CoV-2 virus. Additionally, there is a hypothesis that some of these viral peptides may replicate by hijacking cellular functions, although further research is needed to validate this.
Viruses exhibit a wide range of genomic structures, with +ssRNA viruses being the most common in eukaryotes. These viruses pose significant threats to human, animal, and plant health, causing diseases like COVID-19, dengue, Zika, and foot-and-mouth disease.
Traditionally, it was believed that viral proteins are only encoded by the genomic RNA of +ssRNA viruses, while negative-sense RNA (−RNA) served as a replication intermediate without coding capacity. However, recent research has challenged this belief. Small open reading frames (rORFs) have been discovered within the −RNA of +ssRNA viruses, suggesting that these viruses have coding capacity in their previously overlooked replicative intermediates.
The discovery of hidden proteins within the −RNA of +ssRNA viruses has significant implications for our understanding of viral infections. These proteins have specific subcellular localizations, interact with viral RNA-dependent RNA polymerase, and play critical roles in viral infection. In the case of SARS-CoV-2, several rORFs within its −RNA were found to suppress the production of type I interferon, highlighting their importance in modulating host immune responses.
Viruses have evolved various noncanonical translation strategies, such as internal ribosome entry, to maximize their coding capacity. It is suggested that SARS-CoV-2 and other viruses may use internal ribosome entry sites (IRES) to translate the small rORFs within their −RNA, challenging the conventional view of viral protein translation from genomic RNA.
Interestingly, hidden viral proteins are not exclusive to +ssRNA viruses. Geminiviruses, which are phytopathogenic DNA viruses, have also been found to encode small hidden ORFs with biological functions. This suggests that hidden proteins may be a common feature across diverse virus families, regardless of their genomic structures.
The discovery of hidden viral proteins expands our understanding of viral proteomes and their roles in infection cycles. This prompts a reassessment of the coding potential of viral replicative intermediates and calls for further exploration of hidden proteins in other virus classes. Advancements in technology, such as nanopore sequencing and ribosome profiling, offer opportunities for identifying unknown small proteins from diverse viruses.
In conclusion, the discovery of hidden viral proteins challenges existing beliefs about viral coding capacity and opens up new frontiers in virology. The implications of these findings extend beyond basic research and offer potential for the development of antiviral strategies and therapeutics. Understanding the roles of hidden proteins in infection cycles may lead to innovative approaches for preventing and controlling viral diseases, thereby safeguarding global health.