Prevent viruses from multiplying
According to a study conducted by a group from Stanford University and the University of California, San Francisco, temporarily disabling the synthesis of one protein inside human cells can protect against colds, polio, encephalitis and other viral diseases. The results were obtained on human cell cultures and tested on mice.
Acute respiratory viral diseases (ARVI) that are not associated with the influenza virus most often cause inconvenience within one week. They are the most common infectious diseases in the world, which cost the US economy about $ 40 billion a year. About half of all colds are the result of rhinovirus infections. There are about 160 known serotypes of rhinoviruses. Due to such a large number of serotypes, the formation of persistent immunity to rhinoviruses is almost impossible. Antiviral therapy is also ineffective, as rhinoviruses quickly adapt to environmental conditions and become resistant to drugs.
Researchers have found a way to stop the reproduction of a wide range of enteroviruses, including rhinoviruses, by disabling protein synthesis in cells, which, apparently, is necessary for all enteroviruses to replicate.
Known and dangerous
One of the most famous and dangerous enteroviruses is poliovirus. Before the advent of an effective vaccine in the 1950s, in the United States alone, the virus caused paralysis and death of thousands of children every year. In 2014, a new type of enterovirus, EV-D68, was found to be involved in the development of acute flaccid myelitis. Other enteroviruses can cause encephalitis and myocarditis.
Like all viruses, enteroviruses use proteins in cells that infect to reproduce.
To understand which proteins in human cells play a key role in the replication of enteroviruses, the researchers used specially designed genomic screening. To do this, they created a line of human cells that enteroviruses can infect, and then randomly disabled one gene in each of the cells using a gene editing technique. The resulting culture contained cells deprived of one or another gene in the genome.
Scientists infected the culture with rhinovirus RV-C15, which is known to worsen the course of asthma in children, and then with enterovirus EV-C68, which causes acute flaccid myelitis. In each case, some cells managed to survive the infection and spawn colonies. Scientists were able to determine which gene in each surviving colony was disabled. Although both RV-C15 and EV-D68 belong to enteroviruses, they differ and need different proteins inside the host cell for replication. But the absence of several separate genes suppressed the ability of both viruses to penetrate into cells and multiply. One of these genes stood out in particular, it encodes the enzyme methyltransferase SETD3.
Scientists have created a culture of human cells without the SETD3 gene and tried to infect them with several different types of enterovirus – EV-D68, poliovirus, three different types of rhinovirus and two varieties of Coxsackie virus. None of these viruses could replicate in cells with SETD3 deficiency.
The researchers observed a 1000-fold decrease in the rate of virus replication in human cells without SETD3 compared to the control. Knockout of SETD3 in human bronchial epithelial cells infected with various rhinoviruses and EV-D68 reduced replication by about 100 times.
Stable mice
Modified mice with a complete absence of SETD3 grew to adults outwardly healthy, preserving fertility. However, they were immune to two different enteroviruses that cause paralytic encephalitis, even when these viruses were injected directly into the brains of mice shortly after their birth.
SETD3 methyltransferase is used by cells for daily enzymatic activity. Its absence made it impossible to replicate enteroviruses. Instead, they surrounded a protein whose interaction with a part of the SETD3 molecule in some unknown way is necessary for their replication.
The results obtained give hope that one day it will be possible to develop an antiviral strategy not only for the treatment of acute respiratory viral infections, and, possibly, all enterovirus diseases.
Article by J. Diep et al. Enterovirus pathogenesis requires the host methyltransferase SETD3 published in the journal Nature Microbiology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Stanford Medicine: In human cells and mice, a cure for the common cold, Stanford-UCSF study reports.