Science Advances discovers new coronavirus adenovirus vaccine DNA invasion mechanism

Adenovirus causes human respiratory diseases and has been used as a vehicle for vaccination for many years, for example to fight against Middle East Respiratory Syndrome (MERS) and Ebola virus
.

Some Covid-19 vaccine based on replication-defective adenovirus, including AstraZeneca, Johnson & Johnson, CanSino Biologics and Sputnik V.

Viral proteins increase the stability of virus particles

Researchers are developing a key feature of adenoviruses, which is that they can infect human cells and transfer foreign DNA into the nucleus of these cells
.

A new study led by Urs Greber, a professor in the Department of Molecular Life Sciences at the University of Zurich (UZH), shows that this process has evolved a complex mechanism

The protein coat prevents cells from recognizing invading foreign DNA and activates the alarm system
.

Once the virus particle reaches the nuclear pore complex (the passage into the nucleus), the viral DNA is released into the nucleus, where the cellular machinery reads genetic information to produce related proteins

Early release of DNA activates anti-virus alert system

UZH scientists have proven that adenoviruses lacking V protein are not only more unstable than ordinary adenoviruses, but also release their DNA prematurely before reaching the nuclear pore complex
.

Graber said: "This can reduce infection, trigger a response, and activate the immune system

In vector-based vaccines, the protective protein shell surrounding the DNA allows the particles to reach the nuclear pore complex, where the viral DNA is released
.

This "unenvelope" is absolutely necessary for the success of nuclear import and vector-based vaccination, because the nuclear pore complex can prevent large viral particles from invading the nucleus

Prevent viral infections and improve gene therapy

In order to prove this key function of Mind bomb1, researchers used conventional adenovirus to infect human cells lacking Mind bomb1 and a mutant virus containing protein V, which cannot be modified by this enzyme
.

In both cases, the nuclear introduction of viral DNA is defective, and virus particles accumulate in the nuclear pore complex

Urs Greber said: "Our results have stimulated the development of antiviral strategies and strengthened procedures for gene transfer to diseased cells for clinical treatment
.

" It is worth noting that adenovirus has many uses, including as a DNA vector in Gene editing in genetics, metabolic diseases and cancer

Original title:

A viral ubiquitination switch attenuates innate immunity and triggers nuclear import of virion DNA and infection