doi: 10.15389/agrobiology.2018.6.1093eng

UDC 636.2:577.212.3

 

CELLULAR AND EXTRACELLULAR LEVELS OF RETROVIRUS—HOST INTERACTIONS ON THE EXAMPLE OF THE BOVINE LEUKOSE VIRUS.
1. CELL PENETRATION AND INTEGRATION INTO THE HOST GENOME (review)

V.I. Glazko1, 2, G.Yu. Kosovskii2, T.T. Glazko1, 2, I.M. Donnik3

1Timiryazev Russian State Agrarian University—Moscow Agrarian Academy, 49, ul. Timiryazevskaya, Moscow, 127550 Russia,e-mail vigvalery@gmail.com (✉ corresponding author), tglazko@rambler.ru;
2Afanas'ev Research Institute of Fur-Bearing Animal Breeding and Rabbit Breeding, 6, ul. Trudovaya, pos. Rodniki, Ramenskii Region, Moscow Province, 140143 Russia, e-mail gkosovsky@mail.ru;
3Ural State Agrarian University, 42, ul. Karl Libknecht, Ekaterinburg, 620075 Russia, e-mail ktqrjp7@yandex.ru

ORCID:
Glazko V.I. orcid.org/0000-0002-8566-8717
Glazko T.T. orcid.org/0000-0002-3879-6935
Kosovskii G.Yu. orcid.org/0000-0003-3808-3086
Donnik I.M. orcid.org/0000-0002-8593-7470
The authors declare no conflict of interests

Received July 9, 2018

 

Diagnosis and prevention of the retroviral infection spread among farm animals still remain poorly developed primarily due to the fact that a hierarchic cascade of the events which underlie the retrovirus—host interactions involves molecular, intracellular levels, including  cell organelles, and extracellular levels associated with the function of cellular immune networks. This paper presents an overview of own and literature data on the interaction of retroviral pathogen on the example of bovine leukemia virus (BLV) with intracellular structures of target cells. Here we consider four stages of the cascade of the events promoting pathogen, including i) introduction into the cell cytoplasm, ii) the synthesis of DNA copies of the viral genome RNA, iii) their transport into the cell nucleus, and iv) provirus DNA introduction into the host genome. The host genes interacting with viral structures are revealed at each stage. Two key processes contribute to genetic variability of retrovirus genome during infectious cycle: two viral RNAs dimerization needed for reverse transcription increases the frequency of recombination between RNA chains (N. Dubois et al., 2018), and provirus cDNA integration into the host genome can lead to activation of mutational and epigenetic events in both the pathogen genome and the host genome (A. Melamed et al., 2018). BLV pathogenesis is divided into two steps, the infectious cycle of mass infection of host target cells and sequential selection of individual infected cell clones. The peculiarity of the integration sites of the host genome is an increased frequency of mobile genetic elements originally closely related to exogenous retroviral infections (N.A. Gillet et al., 2013; T. Miyasaka et al., 2015). The high density of mobile genetic elements is characteristic of the host genomic DNA fragments flanked by inverted repeats of microsatellite AGC and identification sequence of the DNA transposon Helitron. The multiplicity of intracellular targets, whose polymorphism may be the basis of resistance to retroviral infections, allowed us to assume for the first time that the universal critical factor of the infectious process is the integration of proviral DNA into the host genome. It is suggested that the increased sensitivity of cells to productive BLV infection is due to a decrease in the activity of mechanisms involved in the genome protection from transposition activity. In the next communication, we will discuss the relationship between BLV-infected cells and host immune cell networks, which can also have a determining effect on the development of retroviral-induced infection.

Keywords: retrovirus, bovine leukemia virus, infectious cycle, B lymphocytes, bovine leukemia virus receptor, reverse transcriptase, integrase, mobile genetic elements.

 

Full article (Rus)

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