About 8% of human DNA originates from viruses. They are residue of ancient struggle between our ancestors and infectious virus. These so-called endogenous viruses are often considered as junk DNA without clear biological significance. But scientists from the University of Utah School of Medicine confirm in a new study that evolving and changing the functions of some viruses can making it as a weapon against the virus itself.
In the paper published on March 4 in the journal Science, scientists reported to have found that some viral DNA fragments embedded in our genome regulate some genes which are basic elements of our innate immune system. The innate immune system is the first line of defense which helps the body fight against a number of pathogens including viruses. When using the experimental method to remove some of the exogenous sequence fragments, the defense system will be seriously damaged.
Co-senior author Dr. Cédric Feschotte, associate professor of human genetics said, "We have confirmed that some of the endogenous viruses shape our biology. In mammalian genome, viral DNA repository promotes the updates of innate immune system."
Human capacity of the innate immune system to fight foreign invaders depends on a coordinated response. When infected, cells release interferon to issue a silent alarm. This molecular signal will trigger adjacent cells to activate arsenal consisting of hundreds or thousands of genes to fight against the invaders. By analyzing the public and available genome datasets of human cells, the authors found that interferon seems to activate thousands of endogenous retroviruses (ERV). Since these retroviruses were inserted urgently into our genome millions of years ago, they lost the ability to generate infectious viral particles long ago. Their location in the genome provides clues information about this interferon inducing element of modern functional potential. Not randomly distributed, they are concentrated in some of the nearby genes known to function in immunity.
Feschotte said, "This is the first evidence shows us, some elements really involved in the immune genes turned on." Feschotte and associate professor of human genetics Nels Elde co-senior author of the paper, the paper is postdoctoral Edward Chuong the main author.
To test the viral DNA fragment is indeed vital to the immune, scientists are using gene editing tools CRISPR / Cas9 delete one by one in a number of cell culture virus sequences which are located in the vicinity of the known immune genes. In the absence of exogenous sequence mutant cells cannot respond to interferon immune genes adjacent to properly open, it confirmed that they serve as a switch-borne virus. In addition, when infected with virus AIM2 cell immune response to viral DNA near the gene deletion element, which significantly reduced the effective implementation of the immune response capabilities. In summary, the results show that the ancient viral DNA is essential for virus infections start against contemporary right defense.
Due to the similarity of the virus-derived switch is embedded in the vicinity of many immune genes, suggesting that they work together to help coordinate our cellular defense. "Cellular interferon response is like an alarm system. We found that the most important in this system some of the switches from the actual ancient virus," Chuong said. The study also found other endogenous retroviruses their "connections" and other mammal’s clues interferon response, which may indicate a wide range of species-specific immune response mechanisms.
Elde said, "the transformation of the innate immune system in which some residual virus was likely not accidental." Rapidly evolving and changing pathogen invasion strategy continue to challenge the immune defense. To keep up with its evolution in the past simply recombinant virus genetic material provided. Many viruses originated as an integral part of the virus replication process into our genome. Evolution reverses the situation and we can benefit from it."
没有评论:
发表评论