Researchers at CSIR-Centre for Cellular and Molecular Biology in Hyderabad report that a human protein called DZIP3 recognises viral genetic material and then switches on the cell’s interferon defences. In their experiments the pathway restricted SARS-CoV-2, chikungunya and Japanese encephalitis viruses. The team, writing in The EMBO Journal, now hopes to find drugs that boost it.
When a virus enters a human cell, the cell’s first task is to notice. Its second is to raise the alarm, by producing interferons, signalling proteins that put the infected cell and its neighbours into an antiviral state. A study from CSIR-CCMB in Hyderabad, reported on 22 October, describes a protein that appears to do both jobs.
The protein is DZIP3. According to accounts of the study published by Telangana Today, NewsMeter and Deccan Chronicle, the CCMB team found that DZIP3 binds viral RNA inside the cell, changes shape to activate itself, moves to the mitochondria and there “tags” and activates immune signalling proteins, setting off production of type-I interferons that restrict viral replication.
The work was led by Dr Santosh Chauhan, senior principal scientist at CCMB, with Dr Rinku Sahu as first author, and was funded by the Department of Biotechnology. It is published in The EMBO Journal, a peer-reviewed journal of the European Molecular Biology Organization.
How cells detect viruses
The innate immune system relies on sensors that recognise molecular features common to many pathogens. For RNA viruses, the best-known sensors are RIG-I and MDA5, which detect viral RNA in the cytoplasm. Once activated, they signal through an adaptor protein on the outer membrane of mitochondria, called MAVS, which in turn drives production of type-I interferons such as interferon-beta. This explains why mitochondria, better known as the cell’s power plants, are also a hub of antiviral signalling.
Sensors and signal-amplifiers are usually separate proteins. What makes the CCMB finding notable, as described in the reports, is that DZIP3 seems to combine both functions: it detects viral RNA directly and then acts on the signalling machinery itself. Dr Chauhan said the team had proposed about seven years ago that some human proteins might play this dual role.
DZIP3 was already known to biologists as an RNA-binding protein with E3 ubiquitin ligase activity, meaning it can attach small ubiquitin tags to other proteins and change their behaviour; earlier work had linked it to cell-cycle control in cancer. The reported “tagging” at the mitochondria is consistent with that enzymatic role, although the reports do not identify which proteins DZIP3 modifies.
Three viruses, one pathway
According to the reports, the DZIP3 pathway protected against three viruses of direct relevance to India:
- SARS-CoV-2, the coronavirus that causes COVID-19
- Chikungunya virus, a mosquito-borne virus that causes debilitating joint pain and has caused repeated outbreaks across India
- Japanese encephalitis virus, a mosquito-borne cause of brain inflammation that remains a significant public-health problem in parts of India, despite vaccination
These viruses belong to three different families, which is why the authors describe the mechanism as potentially broad-spectrum.
“Uncovering these natural cell defence mechanisms opens up exciting new possibilities,” Dr Chauhan said, as quoted by NewsMeter.
Why early detection matters
The speed of this first response can shape the course of an infection. During the COVID-19 pandemic, several research groups found that patients with delayed or impaired type-I interferon responses, including some with inherited defects or with antibodies that neutralise their own interferons, were more likely to develop severe disease. A virus that replicates unnoticed for the first day or two gains a head start that the rest of the immune system may struggle to recover. Understanding every sensor that feeds the interferon alarm, and how it might be strengthened, is therefore of more than academic interest.
From mechanism to medicine
The CCMB team says it is now developing small-molecule drug candidates that would enhance DZIP3 activity, strengthening the body’s own antiviral response rather than attacking a particular virus.
The appeal of such “host-directed” antivirals is clear. Most antiviral drugs target a specific viral enzyme, which means a new drug is needed for each virus and resistance can emerge. A drug that amplifies a natural sensor could, in principle, be useful at the start of an outbreak caused by a new or poorly characterised virus, before specific treatments exist.
The challenges are equally clear. Interferon responses are powerful and must be tightly controlled; excessive or prolonged activation causes inflammation and tissue damage, and is implicated in autoimmune diseases. Any drug that boosts DZIP3 would need to raise defences without tipping the immune system into harm. Some viruses also carry proteins that block interferon signalling, which could blunt the effect.
What the reports do not say
NSH was unable to locate the paper itself, and none of the published accounts gives its title, DOI or full author list. Important details therefore remain unconfirmed:
- Whether the experiments used human cell lines alone, primary cells or animal models
- How large the protective effect was
- Which mitochondrial proteins DZIP3 acts on, and whether it interacts with the established RIG-I–MAVS pathway or works alongside it
The phrase “protected against” should be read in that light. Laboratory evidence that a pathway restricts viral replication in cells is an important first step, but it is some distance from showing protection in a living organism, and further still from a therapy.
Why it matters for Hyderabad
CCMB has a long record in molecular and cell biology, and its scientists played a central role in India’s COVID-19 genome sequencing and testing. A paper in a leading molecular-biology journal on a fundamental question in innate immunity is the kind of result that builds that reputation. It also adds to Hyderabad’s position as a centre for infectious-disease research, alongside its vaccine manufacturers.
What happens next
The immediate next step is scrutiny of the published data by other laboratories, followed by attempts to replicate and extend the findings. Drug discovery against a new target typically takes years before any candidate reaches clinical trials.
