The secret room a giant virus creates inside its host amoeba
Uncovering a subcellular environment specialized for efficient viral translation
Kyoto University
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How a mismatch between the virus’s codon usage and the host's genome can hinder viral translation.
view moreCredit: Ruixuan Zhang
Kyoto, Japan -- A virus relies on the host's translation machinery to replicate itself and become infectious. Translation efficiency partially depends on the usage of a codon, or sequence of three nucleotides, that matches the cellular pool of tRNA, key molecules in translation. Using rare codons that are poorly supported by the cellular tRNA pool tends to induce ribosome pausing and mRNA instability, often weakening the virus.
Yet many eukaryotic viruses use a codon pattern that deviates from their host's while still relying on the host's translation mechanism. Theoretically this mismatch should hinder viral mRNA translation, but these viruses may have found a way to alleviate this unfavorable translation condition during infection. To understand how this happens, an international team of researchers, including a team from Kyoto University, decided to investigate.
The team focused on the giant virus Acanthamoeba polyphaga mimivirus, or APMV. This virus has a genome rich in AT sequences but a GC content of only 28 percent, while the amoeba that hosts this virus has a GC content of 58 percent. To identify the dynamics of this viral infection, the researchers examined APMV-infected amoeba cells using a combination of sequencing methods, including Ribosome profiling to estimate the frequency of translation pausing and tRNA sequencing to determine tRNA composition.
The Ribosome profiling data revealed a counterintuitive result: ribosome pausing events were less frequent on viral mRNAs than on host mRNAs despite the mismatched codon usage. Initially, the researchers predicted the tRNA pool would change after viral infection to favor the AT-rich viral mRNA translation, but subsequent analyses uncovered no significant changes.
Instead, the research team discovered a subcellular environment specialized to translate viral mRNAs. In this organelle-like structure, codons frequently used by the virus are more accessible to tRNA than the same codons on the host mRNAs, alleviating the mismatch between codon supply and demand.
This heterogeneous strategy is completely different from the homogenous strategy of bacterial viruses, which tend to employ the same codon as their hosts for optimal translation. The researchers speculate this newly discovered local translation mechanism may represent a strategy common to many other viruses, including human pathogens.
"I have always thought that the AT-rich codon usage of APMV is an evolutionary consequence of mutational bias," says team leader Hiroyuki Ogata. "However, our results imply that it may be an adaptive evolutionary strategy to efficiently use cellular resources while avoiding competition with the host."
In the future, the team intends to obtain more data on this subcellular environment and provide a more systematic understanding of the viral infection process.
"Our study naturally leads to many fascinating questions," says first author Ruixuan Zhang. "How is this subcellular environment created? Which specific proteins or RNAs drive its formation? Can this heterogeneous molecular distribution be generalized to other intracellular microorganisms? These are challenging questions I am excited to dive into."
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The paper "A giant virus forms a specialized subcellular environment within its amoeba host for efficient translation" appeared on 9 January 2026 in Nature Microbiology, with doi: 10.1038/s41564-025-02234-x
About Kyoto University
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en
Journal
Nature Microbiology
Method of Research
Observational study
Subject of Research
Cells
Article Title
A giant virus forms a specialized subcellular environment within its amoeba host for efficient translation
Article Publication Date
9-Jan-2026
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