Novel ways of struggling with flu

Hungarian researcher, Péter Horváth, cooperating with scientific group from the Institute of Biochemistry at the ETH Zurich have investigated the role of host cells during the infection of influenza A virus. It appeared that the virus is capable of mimicking host cell component. Because of this, what host cells do is assist in a process of capsid disassemble, which eventually results in entering of viral material into the nucleus. This recently identified mechanism gives hope for development of more efficient treatment directed against flu.

Influenza annual outbreaks occur usually in the winter months causing plenty of people suffering from complications, which sometimes might be really severe. The illness is strongly  contagious and its spread is dependent on several factors such as virus transmissibility or the susceptibility of a particular population.

There exist several types of influenza viruses: A, B and C. Among them, A type possesses significant ability to rearrange its antigenic features, which are envelope glycoproteins, the hemagglutinin (H) and the neuraminidase (N). The subtypes of the glycoproteins are the basis of influenza virus nomenclature e.g. H1N1, popularly known as “swine influenza”. Due to the constant changes in the antigenic characteristics, the strains affecting people are different every year and the elaboration of efficient vaccine remains very challenging.

In the presented study, the researchers have tried to find potential targets for anti-viral drugs by analyzing the process of interaction between host cells and viral particles of influenza A. During the process of infection, capsids need to be disassembled before the viral ribonucleoproteins (RNPs) can become synthesized in the nuclei of the cells. The scientists have reported that histone-deacetylase 6 (HDAC6) is one of the major host proteins involved in this phenomenon. HDAC6 acts by connecting the viral capsid proteins with host motor proteins such as actin. Importantly, HDAC6 ubiquitin binding domain seems to be essential for the proper capsid uncoating and eventually efficient infection.

Yohei Yamauchi from the Institute of Biochemistry at the ETH Zurich, who is a co-author of the paper, explains in more detail how the infection can be blocked basing on the depicted mechanism:

“Theoretically in order to block infection, or to dampen it significantly, we want to develop a new drug or a nano-body that blocks the ubiquitin-binding activity of the HDAC6 ZnF-UBP region (which is at the C terminus of HDAC6). Since the structure of this particular domain has been already solved, we are hopeful that a small molecule inhibitor can be generated in time. When the ZnF-UBP is blocked, HDAC6 will not be able to asset the disassembly process of the flu capsid. HDAC6 is not the only cellular factor responsible for capsid disassembly, and we are working on some of those factors in parallel.”

This recent finding opens novel ways of struggling with flu. Researchers are intensively working on the elaboration of molecules that can serve as dugs. “We have recently begun to test delivery of antibodies or nanobodies into cells, which is currently under optimization.” said Yohei Yamauchi. It gives hope that in a not distant future, better approaches for fighting with the virus will be proposed and eventually applied in the clinics.

Sources:

http://www.sciencemag.org/content/346/6208/473.abstract

http://mta.hu/news_and_views/results-of-mta-researcher-to-open-up-new-avenues-in-developing-novel-drugs-against-flu-135293/

http://www.uptodate.com/contents/epidemiology-of-influenza?source=see_link#H1200927955

http://www.webmd.com/cold-and-flu/flu-guide/advanced-reading-types-of-flu-viruses

Maciej Smolarz