EXPRESSION of NK-lysin, blvr, ifn-a AND BLOOD CELL POPULATIONS IN COWS INFECTED BY BOVINE LEUKEMIA VIRUS

Abstract

At now, it is impossible to prevent or control the spread of retroviral infections, in particular, bovine leukemia virus (BLV). The existing methods of vaccination and detection of infected animals remain insufficient (G. Gutiérrez et al., 2014; M. Nishiike et al., 2016) which necessitates further investigations of the interactions between pathogen and host organism. Previously, we obtained evidence that a common characteristic for BLV infected animals with moderate and high leukocytosis was the increase in platelets, and in cows with a pronounced leukocytosis the decrease in the number of neutrophils (G.Yu. Kosovovskii et al. 2017). In order to assess the relationship between BLV infection in animals, the ratio of cell populations in the peripheral blood and the expression of the genes, encoding the BLV receptor (blvr gene), a comparative analysis of antivirus protection protein, interferon alpha (INFΑ), and effector protein of innate immunity, NK-lysine, was carried out in two groups of cows that differed in origin and farm conditions. In result, the evidences were obtained that cows from two farms differed mainly in the amount of peripheral blood neutrophils and platelets. However, in both farms the BLV infected animals had the reduced gene expression of NK-lysine and an increased number of platelets compared to cows free from infection. Relatively increased expression of blvr was observed in BLV infected cows, reflecting, apparently, the increase in the proportion of the young forms of B-lymphocytes (M. Lavanya et al., 2008). On the basis of the own obtained findings and literature data the scheme is proposed of the influence of BLV on the expression of NK-lysine and the suppression of apoptosis. As per the scheme, viral protein TAX (a transcription activator) induces the expression of host tnf- gene (M. Arainga et al., 2012) which, in turn, activates the Treg regulators of immune homeostasis (L.Y. Chang et al., 2015); Treg produces TGF-β (transforming growth factor beta), TGF-β inhibits the proliferation and activity of T-killers and NK-cells, the producers of NK-lysine, and increases the number and activity of platelets which inhibits the apoptosis (K. Ohira et al., 2016; S.C. Tao et al., 2016). The proposed scheme suggested that the key event in pathogenesis, induced by BLV, is the effect on the innate immune system.

Leukocytosis and Expression of Bovine Leukemia Virus microRNAs in Cattle

“…Interestingly, there were also correlations between blvr, pol, dc1, and ago2 gene expressions ( Table 6). In our previous studies, blvr gene expression was also increased in BLV infected animals; however, its expression didn't correlate with other features (16). Generally, blvr is highly expressed in juvenile lymphocytes and its expression gradually decreases during terminal differentiation (19).…”

“…In our previous studies, we demonstrated that cows, which are infected with BLV virus, have lower NK-lysin gene expression (that is the functional marker of T and NK killers) and have an increased thrombocyte count as compared to uninfected cows (16). It could indicate that the major BLV-induced infection event is the suppression of the host immune system.…”

CELLULAR AND EXTRACELLULAR LEVELS OF RETROVIRUS—HOST INTERACTIONS ON THE EXAMPLE OF THE BOVINE LEUKOSE VI-RUS. 2. CRITICAL STAGES — MULTIPLICITY AND VERSATILITY (review)

“…К о м п л е к с н о с т ь в з а и м о д е й с т в и я о б о л о ч е ч н ы х б е л к о в в и р у с а с б е л к а м и п л а з м а т и ч е с к о й м е м б р а н ы к л е т о к х о з я и н а. Ранее мы рассматривали основы и последствия связывания оболочечного белка BLV, кодируемого геном env, с клеточным рецептором адаптерного комплекса (adaptor-related protein complex-3 -AP-3), участвующего в транспорте белков в лизосомы (3). Нами было обнаружено, что у инфицированных BLV коров экспрессия гена, кодирующего рецептор AP3D1, выше, но она не коррелирует с увеличением количества лимфоцитов, что обычно рассматривается как предлейкозное состояние (4). Другой мишенью рецепции продуктов гена env BLV, способствующей слиянию инфицированных и свободных от инфекции клеток, служит трансмембранный транспортер катионных аминокислот SLC7A1/CAT1 (5,6).…”

“…Известно, что Tax индуцирует увеличение экспрессии многих генов хозяина, в частности фактора некроза опухолей альфа -TNFα (67,68). В наших собственных исследованиях было обнаружено, что одним из наиболее общих изменений у инфицированных BLV коров (независимо от происхождения и хозяйств, в которых они содержались), кроме различий в количестве тромбоцитов (69), оказалось уменьшение экспрессии NK-лизина -одного из основных белков цитотоксических гранул Т-киллеров и NK-клеток, что отражает угнетение факторов врожденного иммунитета (4).…”