Navigation Links
Getting wise to the influenza virus' tricks
Date:5/4/2008

Influenza is currently a grave concern for governments and health organisations around the world. The worry is the potential for highly virulent bird flu strains, such as H5N1, to develop the ability to infect humans easily. New drugs and vaccines to halt the spread of the virus are badly needed. Now one of the tactics used by influenza virus to take over the machinery of infected cells has been laid bare by structural biologists at the European Molecular Biology Laboratory (EMBL) and the joint Unit of Virus Host-Cell Interaction of EMBL, the University Joseph Fourier and National Centre for Scientific Research (CNRS), in Grenoble, France. In the current issue of Nature Structural and Molecular Biology they publish a high-resolution image of a key protein domain whose function is to allow the virus to multiply by hijacking the host cell protein production machinery. The findings open the way for the design of new drugs to combat future influenza pandemics.

Upon infection the influenza virus starts multiplying in the cells of its host. One protein that is crucial in this process is the viral polymerase - the enzyme that copies its genetic material and helps to produce more viruses. One component of the polymerase, called PB2, plays a key role in stealing an important tag from host cell RNA molecules to direct the protein production machinery towards the synthesis of viral proteins. Researchers of the groups of Stephen Cusack and Darren Hart at EMBL Grenoble have identified the PB2 domain responsible for binding the tag, produced crystals of it and examined them with the powerful X-ray beams of the European Synchrotron Radiation Facility (ESRF).

Viruses are masters of cunning when it comes to hijacking the normal functioning of the host cell. The influenza virus steals a password from host messenger RNAs, molecules that carry the instructions for protein production, and uses it to gain access to the cells protein-making machinery for its own purposes, says Cusack.

The password is a short extra piece of RNA, a modified RNA base called a cap, which must be present at the beginning of all messenger RNAs (mRNAs) to direct the cell's protein-synthesis machinery to the starting point. The viral polymerase binds to host cell mRNA via its cap, cuts the cap off and adds it to the beginning of its own mRNA a process known as cap snatching. The capped viral mRNA can then be recognised by the host cell machinery allowing viral proteins to be made, at the expense of host cell proteins.

The atomic resolution image the EMBL scientists generated of a PB2 domain bound to a cap reveals for the first time the individual amino acids responsible for recognising this special structure. The central interaction is a sandwich with two PB2 amino acids stacking either side of the cap. Whilst this recognition mechanism is similar to other cap-binding proteins, its structural details are distinct. Collaborators at the Centro Nacional de Biotecnologia in Madrid showed that disruption of the PB2 cap-binding site prevents the influenza virus from replicating.

These findings suggest that the PB2 cap-binding site is a very promising target for anti-influenza drugs, Hart says. Our new structural insights will help us design mimics of the cap that would inhibit viral replication and hence reduce the spread of virus and the severity of the infection.


'/>"/>

Contact: Anna-Lynn Wegener
wegener@embl.de
49-622-138-7452
European Molecular Biology Laboratory
Source:Eurekalert

Related biology news :

1. The sea ice is getting thinner
2. Tamiflu effective for treatment and prevention of influenza in children 1 year and older
3. Influenza vaccine causes weaker immune response for children of rural Gabon than in semi-urban areas
4. New field-deployable biosensor detects avian influenza virus in minutes instead of days
5. St. Jude influenza survey uncovers key differences between bird flu and human flu
6. Viruses may play a role in lung cancer development
7. Ugandan monkeys harbor evidence of infection with unknown poxvirus
8. Viruses, oxygen and our green oceans
9. Vaccine for Ebola virus
10. Surprising discovery from first large-scale analysis of biodiversity and biogeography of viruses
11. Biologists surprised to find parochial bacterial viruses
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/22/2017)... 2017 With the biometrics market to ... four technologies that innovative and agile startups must ... in the changing competitive landscape: multifactor authentication (MFA), ... "Companies can no longer afford to ... Dimitrios Pavlakis , Industry Analyst at ABI ...
(Date:2/14/2017)... , Feb. 14, 2017  Wake Forest Baptist ... as its new chief executive officer (CEO). Freischlag joins ... John D. McConnell , M.D., who last year ... at the Medical Center, after leading it since 2008. ... full scope of Wake Forest Baptist,s academic health system, ...
(Date:2/9/2017)... , Feb. 9, 2017 The biomass ... analysis of the biomass boiler market globally in terms ... of biomass boilers. The market for biomass boilers has ... type, end-user, application, and country/region. The market based on ... & forest residues, biogas & energy crops, urban residues, ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... , March 23, 2017  SeraCare Life ... global in vitro diagnostics manufacturers and clinical ... industry,s first multiplexed Inherited Cancer reference ... by next-generation sequencing (NGS). The Seraseqâ„¢ Inherited ... with input from industry experts to validate ...
(Date:3/23/2017)... MENLO PARK, Calif., March 23, 2017  BioPharmX ... developing products for the dermatology market, today reported ... Jan. 31, 2017, and will provide an update ... from the year. "We are pleased ... productive year for BioPharmX," said President Anja Krammer. ...
(Date:3/23/2017)... March 23, 2017 Kineta, Inc., a ... novel therapies in immuno-oncology, today announced the discovery ... molecule compounds that activate interferon response factor 3 ... demonstrate immune-mediated tumor regression in a murine colon ... who demonstrated complete tumor regression to initial drug ...
(Date:3/23/2017)... New York , March 23, 2017 ... blood plasma products and derivatives market is fragmented due to the presence ... players, such as Proliant, Thermo Fisher , and Sigma-Aldrich, compete ... leader, these three companies, collectively, held more than 76% of this ... ...
Breaking Biology Technology: