March 8, 2017 Enterovirus 71 infected cells: with the cell nuclei stained blue while the virus proteins are stained green. Credit: A*STAR Institute of Molecular and Cell Biology
The unavailability of antiviral medicines and vaccines has made outbreaks of hand, food and mouth disease (HFMD) caused by enterovirus 71 (EV71), a serious threat that affects millions worldwide. Now, an A*STAR comprehensive study has identified which human proteins in a cell are hijacked by EV71 and which try to resist its invasion. Clarifying these host-pathogen interactions could reveal new targets for antiviral therapeutics.
EV71 infections mainly affect children and can lead to aseptic meningitis, and long-term neurological complications, including polio-like paralysis. Since the EV71 genome encodes for just 11 proteins, it has cleverly evolved to exploit human cells to its advantage and guarantee its successful replication.
To check which human proteins facilitate or hinder EV71 replication, scientists at the A*STAR Institute of Molecular and Cell Biology have developed a gene 'atlas'. They screened 21,121 human genes, using a technique called small interfering RNA (siRNA). The team reported an extensive list of known and unknown classes of genes that play a role during EV71 infection.
Among the 256 so-called 'host factors' identified, several proteins help regulate the length of different stages of the cell cycle, like aurora kinase B (AURKB) and cyclin-dependent kinase 6 (CDK6). Interestingly, the virus seems to manipulate these proteins to favor its own replication. For example, by evicting CDK6 out of its workplace, the nucleus of the cell, EV71 could extend certain stages of the cell cycle to its own benefit.
Another sly mechanism used by this virus is to interfere with the cellular quality control process that discards abnormal or wrongly manufactured proteins. In this way, viral proteins can be produced inside the human cell, undisturbed.
The scientists focused on two host factors that were both shown to assist EV71 replication: N-glycanase 1 (NGLY1) and valosin-containing protein (VCP). Drugs that inhibit these two host factors also reduce the number of EV71-infected cells. VCP is probably held inside vesicular structures used by the virus to copy its genome, but it remains unknown how EV71 benefits from NGLY1.
"This is the first genome-wide siRNA screening for EV71-human factors interaction and reveals the complex interplay between the virus and the proteins of a specific human cell line," points out Justin Jang Hann Chu, lead author of the study. "Some host factors we found are shared with picornaviruses and enteroviruses infections, while others are completely new and need to be further explored. This information opens a new chapter in the development of antiviral strategies for HFMD."
Explore further: Novel mechanism for invasion of EV71 virus demonstrated
More information: Kan Xing Wu et al. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication, Nature Communications (2016). DOI: 10.1038/ncomms13150
A new study determines glycosylation and pH-dependent conformational changes of virus receptor SCARB2 as crucial for EV71 attachment, entry and uncoating.
The first enterovirus 71 (EV71) vaccine candidate to reach phase 3 clinical testing provides young Chinese children with significant protection against disease caused by EV71, a growing public-health threat which has caused ...
(Phys.org)Viruses are just bits of DNA or RNA and proteins, but they have proved to be capable of immense destruction to human health. How have they achieved the ability to create such devastating diseases in organisms ...
Researchers have discovered critical new details about the structure of a virus that causes potentially fatal brain swelling and paralysis in children, pointing toward designs for antiviral drugs to treat the disease.
Viral replication and spread throughout a host organism employs many proteins, but the process is not very well understood. Scientists at A*STAR have led a collaborative study to learn which host factors play a key role in ...
Researchers have discovered a potential treatment for a viral infection that causes potentially fatal brain swelling and paralysis in children. The findings also point to possible treatments for related viruses including ...
The International Potato Center (CIP) launched a series of experiments to discover if potatoes can grow under Mars atmospheric conditions and thereby prove they are also able to grow in extreme climates on Earth. This Phase ...
EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human ...
An international research team has discovered a biochemical pathway that is responsible for the development of moss cuticles. These waxy coverings of epidermal cells are the outer layer of plants and protect them from water ...
A new study involving biologists from Monash University Australia has found that despite their very different ancestors, dolphins and crocodiles evolved similarly-shaped skulls to feed on similar prey.
A new study by G. William Arends Professor of Microbiology at the University of Illinois Bill Metcalf with postdoctoral Fellow Dipti Nayak has documented the use of CRISPR-Cas9 mediated genome editing in the third domain ...
Proteins, those basic components of cells and tissues, carry out many biological functions by working with partners in networks. The dynamic nature of these networks - where proteins interact with different partners at different ...
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Read the original:
Genetic screening to fight the common childhood virus that causes hand, foot and mouth disease - Phys.Org