Researchers have discovered an entirely new infection route for influenza A viruses. While all previously known influenza A viruses bind sialic acid moieties on the host cell surface, the recently discovered bat-derived influenza A virus subtypes infect human and animal cells by utilizing MHC class II proteins. The immunologically relevant MHC class II molecules are ubiquitously found in many animal species, which is why the discovery will play an important role in assessing the risk of spill-over infections to other species than bats. The study, published in the journal Nature, also provides new approaches to the evolutionary genesis of influenza viruses.
"In the lab, bat viruses can use the MHC class II complexes of mice, pigs, chickens, or humans to enter the cell. It is thus not unlikely that these bat-derived influenza viruses could be transmitted naturally from bats to other vertebrates and even humans," says the study and research group leader.
With a two-pronged strategy and a lot of effort, the researchers finally succeeded in finding the cellular factor mediating the virus's entry into the host cell. First, the group compared the proteins produced in infectible cells to those produced in non-infectible cells. Using a technique called transcriptomic profiling, the researchers estimated the amount of cellular proteins via mRNA copies. This approach already provided strong indications for the MHC class II complex as the receptor candidate. Then, the team conducted a screening experiment in which they cut one of a total of 20,000 genes in single cells using the molecular scissor CRISPR-Cas. "Cells in which we switched off MHC class II were immune to infection. That was the final proof that the virus enters the cell with the help of MHC class II molecules," says the virologist.
The discovery of this second, sialic acid-independent, mechanism also raises the question which strategy was first in evolutionary terms. "It is quite possible that the newly discovered route of infection via MHC class II originates from the already known sialic acid pathway," says the author.
The current study also raises new research questions: Are there other influenza viruses that use MHC class II proteins as host cell receptor? How simple can influenza viruses switch their receptors, and is it even possible that influenza viruses emerge, which can infect target cells by both receptors? "These are all questions that we now aiming to investigate, because influenza viruses are evidently more versatile than previously thought," says the virologist.
https://www.uniklinik-freiburg.de/nc/presse/pressemitteilungen/detailansicht/presse/1767.html
https://www.nature.com/articles/s41586-019-0955-3
Sialic acid-independent mechanism of influenza virus entry into the cells
- 1,603 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Harmful protein waste in the muscle from a genetic disorder
Read more
Natural selection opposes sexual selection
Read more
Largescale brain epigenetics study discovers 84 new genes linked to…
Read more
Rescuing the synapse at nerve-muscle junction with antibody therapy
Read more
Controlling neuronal hyperactivity in Bourneville's tuberous sclero…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar