Published Oct 23, 2026 | 4:13 PM ⚊ Updated Oct 23, 2026 | 4:13 PM
DZIP3 is not new to science. It was first identified more than two decades ago because it interacted with RNA from the hepatitis B virus.
Synopsis: Researchers at CSIR-CCMB, Hyderabad, have identified a protein that detects viral RNA and strengthens the body’s antiviral immune response. Published in The EMBO Journal, the study found that DZIP3 helped restrict several viruses in laboratory experiments. Researchers say the discovery could guide future antiviral drug development, but further animal and human studies are needed.
When a virus enters a human cell, a race begins. The cell has to spot the intruder and sound the alarm before the virus makes thousands of copies of itself.
About seven years ago, a research group led by Dr Santosh Chauhan at the CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, began investigating whether certain proteins could do two jobs at once: detect a virus’s genetic material and activate the cell’s defences.
Now, a study published in The EMBO Journal identifies one such protein, DZIP3. The researchers found that it recognises viral RNA and helps switch on the immune response that restricts viral multiplication.
The researchers found that DZIP3 helps cells restrict several RNA viruses. These include SARS-CoV-2, which causes COVID-19, chikungunya virus, influenza A virus and Japanese encephalitis virus. RNA is a molecule that carries genetic information in many viruses.
“DZIP3 depletion impairs host antiviral defense, whereas DZIP3 restricts infection by a broad range of RNA viruses,” the authors write.
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DZIP3 is not new to science. It was first identified more than two decades ago because it interacted with RNA from the hepatitis B virus. Its role in immunity, however, was never explored. “However, its function in viral RNA sensing and innate immunity remained unexplored for two decades,” the authors write.
Innate immunity is the body’s built-in first line of defence. It reacts within hours, before a more targeted immune response develops.
One of the best-known viral sensors in the cell is a protein called RIG-I. When it recognises certain viral genetic material, it helps trigger the production of interferons. These are messenger proteins that warn cells about infection and switch on antiviral genes.
The researchers found that DZIP3 strengthens this process. When it binds to viral double-stranded RNA, which consists of two paired RNA strands, it changes shape and becomes active. It then joins RIG-I and a partner protein called MAVS on the surface of the mitochondria, the cell’s energy factories, where the immune signal is passed along.
Once there, DZIP3 attaches a small molecular tag to RIG-I. The tag helps keep RIG-I from being broken down, so the alarm lasts longer. Scientists call such tagging ubiquitination, and proteins that do it are known as E3 ubiquitin ligases.
The authors describe DZIP3 as “a rare example of a dual-function effector, both a viral dsRNA detector and an executor of antiviral immunity.” Put simply, it is both the smoke detector and the person who rings the bell. It works alongside RIG-I rather than replacing it.
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The two proteins also seem to favour different targets. RIG-I tends to recognise shorter viral RNA pieces with particular chemical features at one end. DZIP3 prefers longer double-stranded stretches.
“DZIP3 and RIG-I may engage complementary RNA recognition mechanisms during authentic viral infection rather than functioning redundantly,” the authors write. If the proteins recognise different forms of viral material, together they could help cells detect a broader range of threats.
The team also checked two other known helpers of RIG-I, called TRIM25 and RIPLET. DZIP3 still worked when those were silenced, suggesting it acts through a distinct route.
A sensor like this must also avoid reacting to the body’s own material, which can cause harmful inflammation. In the experiments, DZIP3 bound strongly to viral double-stranded RNA and only weakly to viral single-stranded RNA. It also showed no significant attachment to the cell’s own double-stranded RNA in the tests performed.
“DZIP3 does not merely bind RNA indiscriminately; rather, it is selectively activated by non-self-viral RNA,” the authors write. “Non-self” simply means material that does not belong to the body.
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To test DZIP3’s role, the team lowered or raised its levels in cells and then infected them.
With vesicular stomatitis virus, a standard laboratory tool, cells with less DZIP3 produced more than ten times as many infectious virus particles as control cells. Cells with extra DZIP3 produced fewer.
The same pattern appeared with the other RNA viruses tested. Across all of them, reducing DZIP3 increased viral replication, while increasing it suppressed replication.
The team also studied gene activity in three types of cells, drawn from blood, colon and bladder tissue. In all three, reducing DZIP3 lowered the activity of many genes involved in antiviral defence. A database analysis predicted that more than 250 interferon-activated genes were turned down in one of the cell types.
This suggests DZIP3 is linked to a wider network of immune activity, not just a single signal. Even so, the experiments do not show how much protection the protein offers against infection in people.
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CSIR-CCMB says Chauhan’s team is developing small-molecule drug candidates intended to boost DZIP3 activity. Small molecules are chemical compounds that researchers may be able to develop into medicines. The aim, according to the institute, is to artificially enhance the body’s natural antiviral immunity.
“Discovering how DZIP3 senses viral RNA and directly triggers the cell’s immune machinery gives us a deeper understanding of human immunity,” said Chauhan, Senior Principal Scientist at CSIR-CCMB. “Uncovering these natural cell defense mechanisms opens up exciting new possibilities, and targeting DZIP3 with small molecules could lead to broad-spectrum antiviral therapies against emerging viral threats.”
A broad-spectrum antiviral is one designed to work against several viruses rather than just one. That would be valuable in a new outbreak, when no specific vaccine or drug is ready.
The statement from CCMB describes candidates under development, not a proven treatment. Any candidate would need to work in animals, show an effective dose, pass safety checks and then be tested in human clinical trials.
The authors also point to a possible opposite use. “Conversely, selective inhibition of DZIP3 could be beneficial in hyperinflammatory conditions or autoimmune diseases where aberrant IFN responses drive pathology,” they write. In such conditions, the immune system either overreacts or attacks the body’s own tissues. The authors suggest that “modulating DZIP3 activity may offer a novel immunotherapeutic axis, balancing immune activation and resolution.”
Significant gaps remain. One is the protein’s structure. “A detailed understanding of the structural dynamics of DZIP3, both in its basal state and upon RNA binding, remains lacking,” the authors write. Specialised imaging methods will be needed to see how it changes shape.
The larger question is whether the mechanism works the same way in a living body. The authors say “future in vivo studies utilizing knockout mouse models will further dissect its precise physiological roles in systemic innate immunity and viral pathogenesis.”
(Edited by Dese Gowda)
