Vol 58, No 1S (2013)

New map signs are introduced and some previously introduced ones are improved for arboviruses, which taxonomy positions were recently specified as the result of implementation of full genome sequencing and metagenomic analysis into laboratory practice.

In the presented article the results of colleagues from D.I. Ivanovsky Institute of Virology devoted to evolution of human influenza viruses, monitoring of their circulation, elaboration of methods for investigations and scientific recommendations for efficacy using of specific means for prophylaxis and treatment of influenza infection are presented. V.M. Zhdanov, whose 100-year anniversary will be celebrated in 2014 was the founder of the most of scientific directions of influenza studies that are continuing in D.I. Ivanovsky Institute of Virology till now. A number of priority developments of D.I. Ivanovsky Institute of Virology has got international recognition. Now D.I. Ivanovsky Institute of Virology has status of both Influenza Ecology and Epidemiology Center and National Center of influenza collaborating with WHO.

In 1990 there was posthumously published monograph “Evolution of viruses” written by famous academician AMS USSR V.M. Zhdanov. In fact, the monograph was an unique attempt to analyze and systematize the representatives of the kingdom of Viruses (Virae) according to their origin and evolution. The end of 1980s was a turning point in the development of virology and preceded the start of the program “Human Genome”. For understanding a role of endogenous retroviruses in a genome of animals and humans remained not a lot of time. But V.M. Zhdanov had made a significant contribution even in this section fundamental virology. So, this article dedicated to the memory V.M. Zhdanov is an attempt to tie the amazing atmosphere of national molecular biology and virology in 1970-1980s with unique discoveries in the field of fate and evolution of intragenome functionalization of viral genomes and their elements of animals and humans. Active development of researches of endogenous retroviruses (ERV) refers to 1960-1970. In that years three ERV types had been identified: avian leukemia virus, murine leukemia virus, and the mouse mammary tumor virus. ERV of primates and humans are represented by a complete integrated copies of viral genomes, pseudogenes and mobile genetic elements of different families: LTR/ERV, LINE, SINE/Alu, SINE/MIR, LTR/ERV. Transcripts of ERV sequences were identified as a miRNAs and non-coding RNAs in total genome transcriptome. Understanding the functions of endogenous retroviruses allowed to explain the central paradox of the human genome: the discrepancy between the information in the genome and the volume of genetic information in the transcriptome. Mobile genetic elements of viral origin have been actively involved in “editing” (remodeling) of the so-called non-coding transcriptome. National studies in this area were far ahead of the time. However, during that period of molecular virology and eukaryotic genome researches have not yet led to the unification of ideas about the origin of viruses and their role in the evolution and structure of the human genome. It is therefore valuable contribution of such scientists as V.M. Zhdanov in the development of this unique field.

This work summarizes our data on mechanisms and consequences of herpes virus infection of male gametes. Viral DNA and proteins as well as herpes simplex virus (HSV) and cytomegalovirus (CMV) infectious activity were revealed in sperm cell fraction. Detection of HSV in sperm was found to correlate with male infertility, miscarriages in female partners and embryo development disturbance. Investigation of virus-cell interaction was performed. Incubation of spermatozoa with herpes viruses in vitro resulted in HSV and CMV localization predominantly on sperm heads. Several models were developed for analysis of herpes viruses effects on spermatogenesis: 1. intraperitoneal infection of prepuberal mice; 2. infection of mature mice via rete testis; 3. human testis organotypic culture infected with herpes viruses. These approaches resulted in: 1. establishment of routes of testicular infection; 2. detection of immature germ cells sensitive for HSV and CMV (spermatogonia, spermatocytes, spermatides); 3. evidence for herpes viruses gametotoxic effect and consequent irreversible loss of fertility; 4. development of experimental method of spermatogenesis restoration based on transplantation of testicular cells from neonatal to adult mice. Results obtained suppose that it is necessary to screen ejaculates from donors and infertile patients for herpes viruses and to develop new approaches for infertility treatment based on combination of antiviral and cell therapies.

The history of the studying of antisense polynucleotides influence on gene functions has more than 30 years. The discovery in the late 1990s the phenomenon of RNA interference has given a new impetus to research in the field of antisense technologies. To date proved that RNA interference is one of the major mechanisms regulating gene activity in eukaryotes, including mammals. The scientific literature contains data directly or indirectly confirming the participation of RNA interference in antiviral immunity in mammals. Tens of drugs based on small interfering RNA (siRNA) for the treatment of somatic and infectious diseases are at different stages of development. Introduction of siRNA-based drugs in clinical practice is limited by several factors, including non-specific siRNA effects on other genes as well as the lack of effective and safe siRNA delivery vehicles. Currently, there are more than 21 drugs on the basis of siRNA reached clinical trials including 4 antiviral drugs. Among the drugs that use the mechanisms of RNA interference none is approved for use. After completion of clinical trials and publication of their results will be possible to more objectively evaluate the prospects of these developments.