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Virus RNA Load in Patients with Tick-Borne Encephalitis, Slovenia.

ABSTRACT: We determined levels of tick-borne encephalitis (TBE) virus (TBEV) RNA in serum samples obtained from 80 patients during the initial phase of TBE in Slovenia. For most samples, levels were within the range of 3-6 log₁₀ copies RNA/mL. Levels were higher in female patients than in male patients, but we found no association between virus load and several laboratory and clinical parameters, including severity of TBE. However, a weak humoral immune response was associated with a more severe disease course, suggesting that inefficient clearance of virus results in a more serious illness. To determine whether a certain genetic lineage of TBEV had a higher virulence potential, we obtained 56 partial envelope protein gene sequences by directly sequencing reverse transcription PCR products from clinical samples of patients. This method provided a large set of patient-derived TBEV sequences. We observed no association between phylogenetic clades and virus load or disease severity.

SUBMITTER: Saksida A

PROVIDER: S-EPMC6038823 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing infections of the central nervous system in central Europe. Previous studies have shown that TBEV exhibits pronounced genetic variability, which is often correlated to the geographical origin of TBEV. Genetic variability of TBEV has previously been studied predominantly in rodents and ticks, while information about the variability in patients is scarce. In order to understand the molecular relationships of TBEV between natural hosts, vectors and humans, as well as correlation between phylogenetic and geographical clustering, sequences of TBEV E and NS5 protein genes, were obtained by direct sequencing of RT-PCR products from TBE-confirmed patients as well as from rodents and ticks collected from TBE-endemic regions in Slovenia. A total of 27 partial E protein gene sequences representing 15 human, 4 rodent and 8 tick samples and 30 partial NS5 protein gene sequences representing 17 human, 5 rodent and 8 tick samples were obtained. The complete genome sequence of TBEV strain Ljubljana I was simultaneously obtained. Phylogenetic analysis of the E and NS5 protein gene sequences revealed a high degree of TBEV variability in patients, ticks and rodents. Furthermore, an evident correlation between geographical and phylogenetic clustering was shown that was independent of the TBEV host. Moreover, we show the presence of a possible recombination event in the TBEV genome obtained from a patient sample, which was supported with multiple recombination event detection methods. This is the first study that simultaneously analyzed the genetic relationships of directly sequenced TBEV samples from patients, ticks and rodents and provides the largest set of patient-derived TBEV sequences up to date. In addition, we have confirmed the geographical clustering of TBEV sequences in Slovenia and have provided evidence of a possible recombination event in the TBEV genome, obtained from a patient.

Dataset Information

Virus RNA Load in Patients with Tick-Borne Encephalitis, Slovenia.

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