⚕️ When a virus carries another: the "Trojan horse" of deltaviruses

Some tiny viruses, called deltaviruses, can only spread by relying on other viruses.

A study published in Cell shows that they can even travel hidden inside the particles of these "helper" viruses, like in a Trojan horse. Thanks to high-resolution imaging and infectivity tests, scientists reveal this unexpected transmission mode, observed with several very different viruses, which could influence the tropism and evolution of these infectious agents.

Viruses dependent on a "helper" virus

For decades, only one deltavirus was truly known: the hepatitis D virus (HDV), which infects humans. This particular virus is classified as a satellite virus, because it depends on other viruses, here hepatitis B, to spread.

Unable to make its own envelope protein, it uses the surface proteins of its partner virus to form infectious particles.

In recent years, however, scientists have discovered many deltaviruses in different animal species. This diversity raised an essential question: how do these viruses transmit and on which partner viruses do they depend?

A viral "Trojan horse"

A study published in Cell reveals a surprising mechanism. Deltaviruses do not just borrow envelope proteins: they can be directly transported inside the particles of another virus.

Scientists describe this process as a viral "Trojan horse". The deltavirus is packaged in the particle of the "helper" virus and thus enters a new cell using the latter's entry point. In other words, the "helper" virus serves as both a vehicle and a passport to allow infection.

Stowaways in viral particles

Concretely, scientists show that deltaviruses can "hitchhike" in the particles of "helper" viruses.

Experiments show that this phenomenon can occur with very different viruses:

• vesicular stomatitis virus (VSV), infecting livestock and transmitted by insects but often used as an experimental model;

• HSV-1, herpes simplex virus type 1, infecting nerve cells in humans;

• a reptarenavirus, a virus infecting snakes.

The fact of observing this mechanism with viruses belonging to very distant families suggests that this mode of propagation could be relatively general among deltaviruses.

A demonstration through imaging and infectivity tests

To demonstrate this mechanism, scientists used an experimental system based on cultured cells. Infected or co-infected cells produce viral particles that can then be analyzed.

Researchers combined several complementary approaches:

• infectivity tests, to verify that the produced particles effectively transmit the deltavirus;

• electron microscopy and super-resolution imaging, allowing the observation of particles compatible with the presence of a deltavirus inside the helper virion.

This strategy linking structure and function allows to show that these particles are not only visible, but they are also capable of ensuring viral transmission.

A new vision of deltavirus biology

Deltaviruses have an extremely small genome. This simplicity makes them highly dependent on other viruses to complete their infectious cycle.

The mechanism of "virus within a virus" constitutes an elegant solution to this constraint: rather than traveling alone, these viruses move concealed in the particles of a partner.

This strategy could influence several important aspects of their biology:

• viral tropism, that is, the types of cells or tissues they can infect;

• host changes, if a deltavirus can use different helper viruses present in a new environment;

• the diversity of deltaviruses, recently revealed in many animal species.

Leads, and open questions

This discovery opens several questions. Scientists now seek to determine if this "Trojan horse" mechanism exists in natural infections and how widespread it is in the viral world.

Understanding how a deltavirus chooses or changes carrier viruses could also shed light on the ecology and evolution of these satellite viruses.

Finally, this work shows that it could be useful to more broadly explore the presence of deltaviruses in humans, potentially in other tissues than the liver and in different clinical contexts.