Hidden viral proteins: How powerful are they?

Viruses are submicroscopic obligate intracellular parasites and usually have tiny genomes.Based on the nature of their genomic nucleic acid and replicative intermediates, viruses may be classified into 7 classes, including positive-sense single-stranded RNA (+ssRNA), negativesense single-stranded RNA (-ssRNA), double-stranded RNA (dsRNA), single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA) viruses, retroviruses, and pararetroviruses.The vast majority of known viruses belong to the +ssRNA class with monopartite, bipartite, or tripartite ssRNA genomes (https://talk.ictvonline.org/taxonomy/).Infection by +ssRNA viruses can cause substantial damage to their host organisms, often leading to severe economic losses and, in some cases, even catastrophic mortality.Examples include human and animal infecting viruses such as acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the ongoing COVID-19 pandemic, dengue, Zika, yellow fever, hepatitis C, foot-and-mouth disease, polio, chikungunya, SARS, and MERS viruses [1].Many plant-infecting +ssRNA viruses, such as tomato brown rugose fruit virus, potato virus Y, plum pox virus, and maize dwarf mosaic virus, cause devastating diseases in diverse crops and threaten global food security.The ssDNA viruses include some of the smallest and simplest viruses, with genomes only approximately 2 to 6 kb in length.Geminiviruses and nanoviruses are 2 known plant ssDNA viruses belonging to the families Geminiviridae and Nanoviridae, commonly known as geminiviruses and nanoviruses, are among the most economically important plant-infecting ssDNA viruses.Due to the small genome size with limited coding capacity, viruses have to rely on host cellular pathways and hijack host factors for infection.On the other hand, viruses have evolved a variety of expression strategies to maximize the coding capacity of their compact genome.These noncanonical translation strategies adopted by viruses include internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshift, and stop-codon readthrough [2].In recent years, "hidden" protein-coding open reading frames (ORFs) with neglected noncanonical translation strategies have been discovered in the genomes of various viruses [1-6].For example, a short ORF encoding a small peptide named P3N-PIPO that is required for viral cell-to-cell movement was found to be embedded within the 5 0 terminal region of viruses in the genus Potyvirus of the family Potyviridae [5]. +ssRNA viruses encode hidden proteins in their -RNAGong and colleaguesAU : Pleasenotethatallinstancesof }etal:}inthemaintexthavebeenchangedto}andcol recently revealed that +ssRNA viruses encode additional functional proteins in their (-)-strand replication intermediates (-RNA) [6], which challenges the current consensus that -RNA lacks coding capacity.This surprising discovery raises an important question: To what extent is this expression mode shared among viruses?

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