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Two dominant species of wild small rodents trapped in Novosibirsk region, South-Western Siberia, Russia differed in their susceptibility to the tick-borne encephalitis virus (TBEV) infection. TBEV RNA average detection rate for Northern red-backed vole Myodes rutilus (Pallas, 1779) (82.2 ± 5.8% blood samples and 63.1 ± 2.7% organ samples) significantly exceeded the corresponding values for the striped field mouse Apodemus agrarius (Pallas, 1771) (47.0 ± 8.7% blood and 24.5 ± 2.8% organ samples) (p <0.001). Innate immunity may be one of possible reasons of the differences. Th1 cytokine gene expression distinguished between M. rutilus (12.5 ± 8.5%) and A. agrarius (66.6 ± 11.4%), whereas Th2 cytokine frequencies were statistically similar (81.8 ± 12.2% and 100.0%, respectively). Polarization indexes (PI) of the innate immunity calculated as ratio of Th2 to Th1 cytokine RNA detection rates for both M. rutilus (6.5) and A. agrarius (1.5) suggested Th2 mainly humoral immune response against persistent TBEV in natural mammalian hosts. Therefore, the TBEV-induced antibodies were analyzed by ELISA and hemagglutination inhibition (HI) tests. The TBEV-specific antibodies were detected in 74.8 ± 4.3% sera of M. rutilus and 67.3 ± 6.8% of A. agrarius. Among them HI antibodies were found in 4.8 ± 2.1% of the same analyzed sera of M. rutilus and in 6.0 ± 3.4% blood samples of A. agrarius only. To model the TBEV persistence both M. rutilus and A. agrarius were infected with the suspensions of the TBEV-infected ticks with further observations during 4 subsequent months. Detection rate of the TBEV RNA and antigen E remained high during the whole period, however, pathogenic for laboratory suckling mice virus was isolated up to 8 days postinfection. At late stages of the persistent infection (1-4 months) the TBEV RNA detection rate in northern red-backed voles remained high 70.6 ± 7.9% whereas in striped field mice significantly declined to 26.7 ± 9.2% (p < .001). Comparative analysis of the innate immunity of the wild rodents in 2 months postinfection showed similar frequencies of Th2 cytokine gene expression for M. rutilus (77.8 ± 10.1%) and A. agrarius (71.4 ± 12.5%) (p > .05) but Th1 cytokine mRNA detection rates were different (44.4 ± 12.5% and 85.7 ± 9.7%, respectively) (p < .05). In 2 months PI decreased from 6.5 until 1.75 for M. rutilus and from 1.5 until 0.83 for A. agrarius. Nevertheless, Th2 mainly humoral immune response was confirmed by direct detection of the TBEV-specific antibodies. HI and neutralizing antibodies were revealed in blood sera of the small rodents of both studied species in 30 days postinfection and remained at detectable levels during 4 months of observations. Accordingly, Th2 polarized innate immunity of small rodents might facilitate the TBEV intracellular persistence in the presence of HI and neutralization antibodies., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Vertical transmission of tick-borne encephalitis virus (TBEV) between generations of the small rodents-red voles Myodes rutilus Pallas (previously known as Clethrionomys rutilus Pallas) was shown for naturally infected reservoir hosts and after experimental infection with different sublethal doses of the viral strains. For wild red voles and for their progeny born in 240-280 days after experimental infection of their parents the TBEV was detected in up to 90% of samples by RT-PCR, ELISA and bioassays. Small amounts of the TBEV RNA found in embryos, placenta and blood cells could serve as evidence of prenatal transmission. Postnatal transfer of the virus might occur through the rodent milk. Analysis of the TBEV E gene nucleotide sequences of RT-PCR products revealed missense mutations resulting in amino acid substitution K280Q in newborn red vole in comparison with its parent female. Taken together, the data confirmed the TBEV vertical transmission among generations of its adapted mammal reservoir hosts. The virus transfer might occur before, during and/or after birth of the small rodents with high frequencies. In the wild it could provide the TBEV long-term persistence in mammal hosts without an (any) involvement of arthropod vectors thus selecting dangerous mammal-adapted variants.

Infestation of small mammals, including common shrews Sorex araneus L., field mice Apodemus agrarius Pallas, and red voles Clethrionomus rutilus Schreber, with immature Ixodes persulcatus ticks and their infection with tickborne encephalitis virus (TBEV) were studied in the forest-steppe habitat in the vicinity of Novosibirsk, Russia. Larval ticks parasitize all three host species, but virtually all nymphs were found only on field mice and red voles. Detection of the viral RNA using reverse transcription (RT) with subsequent nested polymerase chain reaction (nPCR) and of viral antigen using enzyme-linked immunosorbent assay (ELISA) revealed a high prevalence of TBEV-positive animals in both the summer and winter. The proportion of small mammals with hemagglutination inhibition (HI) antibodies was significantly lower than with ELISA-detected antibodies. Taken together, the data suggest that small mammals may maintain TBEV as a persistent infection throughout the year.