Predicting the Evolutionary Variability of the Influenza A Virus.

The influenza A virus remains one of the most common and dangerous human health concerns due to its rapid evolutionary dynamics. Since the evolutionary changes of influenza A viruses can be traced in real time, the last decade has seen a surge in research on influenza A viruses due to an increase in experimental data (selection of escape mutants followed by examination of their phenotypic characteristics and generation of viruses with desired mutations using reverse genetics). Moreover, the advances in our understanding are also attributable to the development of new computational methods based on a phylogenetic analysis of influenza virus strains and mathematical (integro-differential equations, statistical methods, probability-theory-based methods) and simulation modeling.

The progene hypothesis: the nucleoprotein world and how life began.

In this article, I review the results of studies on the origin of life distinct from the popular RNA world hypothesis. The alternate scenario postulates the origin of the first bimolecular genetic system (a polynucleotide gene and a polypeptide processive polymerase) with simultaneous replication and translation and includes the following key features: 1. The bimolecular genetic system emerges not from mononucleotides and monoamino acids, but from progenes, namely, trinucleotides aminoacylated on 3'-end by a non-random amino acid (NpNpNp ~ pX ~ Aa, where N--deoxyribo- or ribonucleoside, p--phosphate, X--a bifunctional agent, for example ribose, Aa--amino acid, ~ macroerge bond).

Effective expression of recombinant cytotoxic protein via its attachment to a polyglutamine domain.

Inadvertent cytotoxicity may hinder the expression of many recombinant proteins that are of industrial or medicinal importance. Here, we show that covalent binding of the influenza A cytotoxic protein M2 to a polyglutamine domain (polyQ-M2; QM2) results in significant delay of its cytotoxic effects when compared to wild-type protein (M2wt). We also show that while expression of recombinant M2wt from A/WSN/1933 strain could not be attained in vaccinia virus (VV), polyQ-M2 was successfully expressed in this system.

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1.

Background: Experimental data accumulated over more than a decade indicate that cross-strain protection against influenza may be achieved by immunization with conserved influenza proteins. At the same time, the efficacy of immunization schemes designed along these lines and involving internal influenza proteins, mostly NP and M1, has not been sufficient.

Objective: To test the immunogenicity and protective efficacy of DNA vaccination with a combination of NP, M1 and NS1 genes of influenza virus.

Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses.

Two-fold immunization of Balb/c mice with a vaccinia virus recombinant expressing the NP protein of influenza A/PR8/34 (H1N1) virus under the control of a strong synthetic promoter induced specific antibodies and protected animals against low-dose challenge by mouse-adapted heterosubtypic variants of human A/Aichi2/68 (H3N2) and avian A/Mallard/Pennsylvania/10218/84 (H5N2) influenza virus strains. The surviving immunized animals had lower anti-hemagglutinin antibody titers compared to non-immunized mice. There was no difference in viral titers in lungs of immunized and non-immunized animals that succumbed to the infection.