The reason for the strong spread of "Delta" has been identified by our scientists!

Although the Omikeron variant has arrived, the Delta variant is still the dominant strain worldwide. From its first discovery to its fiery sweep across the globe, the Delta mutation took only a few months.

Why does the Delta mutation spread so quickly? What makes delta mutants super-fast propagating?

After more than 3 months of "pursuing the murderer", the research team of Professor Huang Bo and Professor Qin Chuan of the Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences finally found out how the Delta variant strain achieved ultra-fast transmission. The relevant research results were published online in the international academic journal "Signal Transduction and Targeted Therapy".

Image source: Visual China

"We found that the Delta variant was able to break through the defense mechanisms of anti-inflammatory alveolar macrophages, and by increasing the number of amino groups, at relatively high pH environments, complete spike protein princation and activate histinases." By cutting the viral spike protein, histase causes the membrane of the viral particle and the membrane of the endocytotic body to split at the contact site, so that the viral RNA is released into the cytoplasm, thereby achieving rapid virus transmission. On December 21, Huang Bo told the Science and Technology Daily reporter.

Due to its high viral load, strong transmission capacity and fast transmission speed, the Delta variant of the new crown virus has rapidly ravaged around the world and become the main strain of the new crown pneumonia epidemic.

"How delta strains with T478K, P681R and L452R mutations spread ultrafastly was previously unclear. This study unravels the mystery of the ultra-fast spread of delta mutants. Huang Bo said.

To understand the transmission mechanism of the Delta strain, we have to start with how the new crown virus infects people.

The respiratory airways of the human lungs expand at the terminal end, forming a balloon-like structure, which is also known as alveoli. Alveoli are places where oxygen and carbon dioxide are exchanged, and there is a thin layer of fluid on the surface to maintain the extension of the alveoli and prevent it from collapsing. When the human body inhales air, it not only sucks oxygen into the alveoli, but also inevitably inhales potential bacteria and viruses in the air into the alveoli.

In order to defend against the invasion of this pathogenic bacteria, immune cells are colonized in the liquid layer on the surface of the alveoli, especially macrophages with phagocytic function, which account for more than 95% of the immune cells settled in the liquid layer, which is medically called alveolar macrophages. These macrophages can engulf particles and microorganisms contained in the inhaled air, keeping the alveoli clean.

Therefore, once the new crown virus enters the alveoli, the alveolar macrophages will immediately engulf the viral particles, forming vesicles with cell membranes wrapped around the viral particles, that is, endocytosis, which in turn fuse with the lysosomes in the cytoplasm, thereby completely degrading the engulfed organisms, including the virus.

However, the new crown virus can use the specific state of alveolar macrophages to escape from the endocytotic small body, and in turn use macrophages to reproduce themselves.

In this regard, Huang Bo explained that this is because the endocytotic ions rely on low pH histinas to be activated, and the histease causes the membrane of the viral particles and the membrane of the endocytosis to split at the contact site by cutting the viral spike protein, so that the viral RNA is released into the cytoplasm. In this way, the new crown virus can achieve rapid proliferation.

Alveolar macrophages will polarize in both pro-inflammatory and anti-inflammatory directions, the pro-inflammatory endophagus body pH is acidic, which can promote histinase activation, while the anti-inflammatory endocytotic body pH is alkaline and can inhibit histonepsin activation.

"A small number of people, whose alveolar macrophages are biased towards the pro-inflammatory type, are susceptible to infection by the new crown virus and are prone to severe disease, but normal people's alveolar macrophages are biased towards the anti-inflammatory type, which can usually inhibit the activation of histase, so as to be able to better resist the invasion of the new crown virus, which is manifested as no disease or mild infection." Huang Bo pointed out.

However, Huang Bo et al. found that the Delta strain was able to break through the defense mechanisms of anti-inflammatory alveolar macrophages.

"The Delta variant is mainly due to changes in multiple amino acids of its spike protein, and the law of change is to increase the amino group. Hist protease activity is closely related to the pH in endocytotic small body. Huang Bo said that low pH can activate histinases, the essence of this process is that the amino group of viral spike proteins is easier to obtain protons, that is, amino protonation.

By increasing the number of amino groups, the Delta strain can complete the spiky protein subration at a relatively high pH, so that it can be cleaved by histease, so that the viral RNA is released, thus achieving rapid transmission.

Huang Bo said that this research helps to provide a target for the development of small molecule drugs, acting on alveolar macrophages, blocking the escape of the Delta variant virus RNA from endocytosis, and then sending the virus into the lysosomal for complete degradation, achieving the effect of prevention and early infection control of the virus.

Source: Science and Technology Daily