For the first time, you can see how a virus enters a cell and infects. Scientists at Harvard Medical School captured live images of engineered viruses doing their thing as they attached to living cells, then injected them with their genomes.
Their findings are published in the journal PNAS.
Viruses infect cells by releasing their genetic material (RNA) into the cytosol, a semiliquid substance inside cells. The RNA can then enter the nucleus, where it replicates before being translated into viral proteins outside the nucleus by ribosomes. These proteins can then assemble to form a new viral particle, which is released from the cell and can infect other cells in the body.
However, before this can happen, the virus must first enter the cell. It does this through a process called endocytosis. First, the virus binds to its target cell, before being engulfed by the membrane, forming a new cell compartment called the endosome. It is from the endosome that the RNA is released into the cell.
Now, we can see these two processes in action.
In the first half of the video, you can see the virus (marked in pink) fusing with the cell membrane, which then forms an endosome. As the virus binds to the endosome membrane, you can see it injecting its RNA (marked in blue) into the cytosol. These are the first steps of viral infection, seen for the first time in real time and in three dimensions.
In the second half of the video, you can see several of the beautiful pink viruses cooling down inside the cell.
To achieve this, the researchers engineered viruses to express spike proteins from SARS-CoV-2, the part of the virus responsible for COVID-19 that allows it to enter cells. They also modified the virus so that the spike protein (labeled “S” in the video) could be tracked separately from the viral content, which itself was labeled with a fluorescent protein (“P” in the video).
The entire process was filmed using lattice light sheet microscopy, an advanced imaging technique.
In addition to this impressive feat, the researchers also found that viruses only fuse with membranes and release their genomes under specific environmental conditions. They require a slightly acidic environment, between pH 6.2 and 6.8, similar to the pH of saliva and urine. Endosomes are also known to be similarly acidic, much like the human nose, the team found.
These acidic environments allow enzymes in endosomes or on the cell surface to cleave the spike protein from the virus, which can then fuse with a membrane. This, the researchers suggest, is happening inside the nose, where COVID-19 infections often start.
“Interestingly, nasal cavity pH measurement has rarely been done before,” co-lead author of the paper Tomas Kirchhausen commented in a statement,
Source: iflscience.com