Over the past few weeks, scientists working on the SARS-CoV-2 coronavirus have gained a better understanding of the virus and its mechanism of infection. Although there are still many gray areas, infectious disease specialists now have a global picture of how the infection works. Benjamin Neuman, a virologist at the University of Texas, has been studying human coronaviruses for more than 20 years. He explains how and why the SARS-CoV-2 coronavirus is of such concern.
A coronavirus infection usually occurs in two ways: either as an infection of the lungs which includes certain cases of what people call the common cold, or as an infection of the intestine which causes diarrhea. COVID-19 begins in the lungs like common cold coronaviruses, but then causes havoc in the immune system that can lead to long-term lung damage or death.
SARS-CoV-2: a virus genetically similar to other human coronaviruses
SARS-CoV-2 is genetically very similar to other human respiratory coronaviruses, including SARS-CoV and MERS-CoV. However, the subtle genetic differences translate into significant differences in how easily a coronavirus infects people and how it makes them sick.
SARS-CoV-2 has the same genetic equipment as SARS-CoV, which caused a global epidemic in 2003, but with around 6000 mutations scattered in the usual places where coronaviruses evolve.
Phylogenetic tree showing the correspondences between the genomes of different coronaviruses. Credits: Peng Zhou et al. 2020
–
Compared to other human coronaviruses such as MERS-CoV, which appeared in the Middle East in 2012, the new virus has customized versions of the same general equipment to invade cells and replicate. However, SARS-CoV-2 has a completely different set of genes called accessories, which give the new virus a little advantage in specific situations. For example, MERS has a special protein that prevents the cell from sounding the alarm about a viral intruder.
The mechanism of infection of SARS-CoV-2
Each coronavirus infection begins with a viral particle, a spherical shell that protects a single long chain of genetic material and inserts it into a human cell. Genetic material forces the cell to make about 30 different parts of the virus, allowing the virus to reproduce. The cells that SARS-CoV-2 prefers to infect have a protein on the outside called ACE2 which is important for regulating blood pressure.
Infection begins when long-tipped proteins protruding from the viral particle cling to the cell’s ACE2 protein. From this point on, the tip is transformed, unfolded and folded up using coiled spring-shaped parts. The reconfigured tip clings to the cell and blocks the viral particle and the cell together. This forms a channel where the chain of viral genetic material can enter the cell.
This illustration, created by the Centers for Disease Control and Prevention (CDC), reveals the ultrastructural morphology exposed by the new coronavirus (SARS-CoV-2). Note the peaks that adorn the outer surface of the virus, which give the appearance of a crown surrounding the virion, when viewed under the electron microscope. The protein particles E, S, M and HE, also located on the outer surface of the particle, have all been indicated. Credits: Wikipedia
–
SARS-CoV-2 spreads from person to person through close contact. The outbreak in Shincheonji Church in South Korea in February provides a good demonstration of the speed of infection and the spread of SARS-CoV-2. One or two people with the virus appear to have been very close to uninfected people for several minutes at a time in a crowded room.
In two weeks, several thousand people in the country were infected and more than half of the cases at that time were attributable to the church. The epidemic started quickly because public health officials were not aware of the potential epidemic and were not doing large-scale testing at this stage. Since then, the authorities have worked hard and the number of new cases in South Korea has continued to decrease.
Viral attack and immune system response
SARS-CoV-2 evolves into type II lung cells, which secrete a soap-like substance that helps air get deep into the lungs and cells lining the throat. As with SARS, most of the damage caused by COVID-19, the disease caused by the new coronavirus, is caused by the immune system deploying a strong defense system to prevent the virus from spreading.
Millions of immune system cells invade infected lung tissue and cause considerable damage when the virus and infected cells are cleaned up. Each COVID-19 lesion ranges from the size of a grape to the size of a grapefruit. The challenge for caregivers who treat patients is to support the body and keep the blood oxygenated while the lung is repairing.
SARS-CoV-2 has a variable severity scale. Patients under the age of 10 seem to be able to clear the virus easily, most people under the age of 40 seem to rebound quickly, but the elderly are more vulnerable. The ACE2 protein that SARS-CoV-2 uses as a gateway into cells is also important for regulating blood pressure, and it doesn’t do its job when the virus arrives. This is one reason why COVID-19 is more serious in people with high blood pressure.
On the same topic: COVID-19: the severity of the infection could depend on your genome
SARS-CoV-2 is more dangerous than seasonal flu in part because it has many more ways of preventing cells from calling the immune system. For example, cells try to respond to the infection by making interferon, the signaling protein.
The SARS-CoV-2 blocks this by a combination of camouflage, cutting off the protein markers in the cell that serve as distress beacons and ultimately shredding any antiviral instructions that the cell produces before they can be used. As a result, COVID-19 can stagnate for a month, causing a little bit of damage each day, while most people overcome a flu case in less than a week.
The persistence of many unknowns
Currently, the transmission rate of SARS-CoV-2 is slightly higher than that of the 2009 pandemic H1N1 flu virus, but SARS-CoV-2 is at least 10 times more fatal. COVID-19 is very similar to Severe Acute Respiratory Syndrome (SARS) in the data currently available, although it is less likely than SARS to be severe.
There are still many mysteries about this virus and coronaviruses in general – how they cause disease, how they interact with proteins inside the cell, the structure of proteins that form new viruses and how some of the basic machines of viral replication work.
Another unknown is how COVID-19 will respond to seasonal changes. The flu tends to follow the cold, both in the northern and southern hemispheres. Some other human coronaviruses spread low throughout the year, but then appear to peak in the spring. But no one really knows why these viruses vary with the seasons.
–
