04 March 2011

Trap the virus

"Nanogorshochki with honey" for deadly viruses
NanoNewsNet based on NIST materials: Using Artificial, Cell-Like 'Honey Pots' To Entrap Deadly VirusesScientists from the National Institute of Standards and Technology (National Institute of Standards and Technology) and Weill Cornell Medical College (USA) have created artificial "protocells" that can attract, capture and inactivate a class of deadly viruses that infect humans.

The method offers a new research tool for a detailed study of the mechanism by which viruses attack cells, and can become the basis for a new class of antiviral drugs.

In an article published in the journal PLOS ONE (Synthetic protocols interact with viral nanomachinery and inactivate pathogenic human virus), scientists describe in detail how new artificial cells achieve almost 100 percent success in deactivating experimental analogues of the Nipah and Hendra viruses, two new genipaviruses (henipaviruses) capable of causing people have the most severe forms of encephalitis (inflammation of the brain), often ending in death.

Genipaviruses belong to paramyxoviruses (Paramyxoviridae) – a large class of human pathogens, other representatives of which are the causative agent of parainfluenza, respiratory syncytial virus, epidemic paratitis and measles viruses. Such viruses are called enveloped, because they are surrounded by a two-layer lipid membrane, similar to that of animal cells.

To infect a host cell, two proteins embedded in this membrane work together. One, the so-called G-protein, acts as a spotter that recognizes and binds to a specific "receptor" protein on the surface of the target cell. Protein G sends a signal to protein F, although the mechanism of transmission of this signal is not yet completely clear. Protein F straightens up like a spring, and with a sufficiently close approach to the cell shoots its "harpoon" into it, penetrating into the two-layer membrane. Then the membranes merge, and the genetic cargo of the virus can be delivered to the cell. However, the virus is able to do this only once.

"We often call our protocells "honey pots" – an attractive, irresistible bait that is used to catch something," says materials scientist David LaVan

The trap protocells have a core of inert but structurally robust nanoporous silica, covered, like any normal cell, with a lipid membrane. In this membrane, scientists have embedded a "bait" – the protein ephrin-B2 (ephrin-B2), a well-known target of genipaviruses. To test its functionality, they exposed the protocells to experimental genipavirus analogues developed at Weill Cornell. Externally, such analogues are almost identical to genipaviruses, but instead of viral RNA, they carry the genome of a non-pathogenic genetically engineered virus that expresses a fluorescent protein after entering the target cell. The fluorescent protein makes it possible to count and visualize infected cells.

A) flat or spherical surfaces of nanoporous silica (SiO2) with a lipid bilayer and EFNB2 protein;
C) the scheme used to confirm the presence and activity of the EFNB2 protein
using purified Hendra G virus (Hendra G) and primary and secondary antibodies
(illustration from the website plosone.org )

Control experiments have shown that protocells are surprisingly effective "baits" that practically purify the tested solution from active viruses. Scientists came to this conclusion by measuring the number of normal cells infected with the remaining virus using a fluorescent protein of their genetically engineered analogue.

The new method is a powerful research tool for studying shell viruses.

"This is a good system for investigating this kind of choreography between a virus and a cell, which was very difficult to study. A normal cell has thousands of membrane proteins. You can study one, but perhaps the results of the experiment are influenced by a completely different one. We reduce an impossibly complex natural cell to a very simple system, so now, by changing its parameters, we can try to figure out how to cheat viruses," Lavan comments on the results of the work.

In the long term, the researchers believe, their protocells may become a new class of antiviral drugs. Viruses are known for their ability to quickly develop resistance to drugs, but since "honey pots" uses the main mechanism of viral infection, any virus that has "learned" to avoid such traps is likely to be less effective in infecting normal cells.

Portal "Eternal youth" http://vechnayamolodost.ru04.03.2011

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