Cellular and extracellular levels of retrovirus-host interactions on the example of the bovine leukose virus. 2. Critical stages - multiplicity and versatility (review)

The wide spread of viral infections and the ease of overcoming the species-specific barriers require the identification of critical stages in the virus interaction with multicellular organisms of mammals and the analysis of key molecular genetic systems involved. To date, a large amount of data has already been accumulated on the diversity and complexity of such systems, as well as the involvement in them the wide range of metabolic pathways. In this regard, attempts to identify some common elements that are implemented in different infectious processes are of particular relevance. This paper is such attempt made on the example of the analysis of the main events of cattle infection by bovine leukemia virus (BLV). Systems involved in the entry of BLV genetic material into the cytoplasm of host cells, the suppression of innate and adaptive immunity, as well as interactions between the genomes of the BLV provirus and the host genome are the identified critical stages. The direct participants in the reception of viral proteins are parts of some host tansmembrane systems (G.Yu. Kosovsky et al., 2017; V.I. Glazko et al., 2018; L. Bai et al., 2019; H. Sato et al., 2020). During virus reproduction in host cells, host enzymes modify virus envelope proteins by (A. De Brogniez et al., 2016; W. Assi et al., 2020). Importantly, modifications of SARS-CoV-2 spike proteins, as well as BLV envelope proteins, have a significant impact on their pathogenicity (M. Hoffmann et al., 2020). Pathogenicity and depressing effect of both BLV and SARS-CoV-2 on innate and adaptive immunity is realized in part through the activation of T regulatory cells and an increase in the expression of the growth transforming factor TGF-b (L.Y. Chang et al., 2015; G.Yu. Kosovsky et al., 2017; W. Chen et al., 2020). Intracellular mechanisms of protection against retrotranspositions, recombinations between viruses and host retrotransposons, the formation of new elements of host regulatory networks such as microRNAs, and the integration of proviral DNA into the host genome are closely related and controlled by interfering RNA (RNAi) systems with the key gene dicer1 (P.V. Maillard et al., 2019; E.Z. Poirier et al., 2021; G.Y. Kosovsky et al., 2020). These systems can provide a certain «resistance» of the host genome both to the integration of exogenous genetic material and to transpositions of own mobile genetic elements. Apparently, it is the polygenicity of the control of these critical stages of viral infection that leads to difficulties in predicting their development and developing methods for their prevention.