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Chapter 5: TBE in adults

phenotypic variability, as well as different infection. The authors of the Russian study
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isoforms of OAS proteins, contributing to the analyzed, in a second step, the frequency of
overall activity in vivo. Several findings from such OAS ‘TBE risk SNPs’ in different ethnic
other viral infections point to an important populations within the territory of the Russian
role of OAS genes in the anti-flaviviral immune Federation. The authors found that the
response. For example, in patients with frequency of the aforementioned SNPs
dengue shock syndrome, transcription levels correlated with the probability of exposure to
of OAS3 in peripheral blood mononuclear cells TBEV. Very low SNP frequencies were
are significantly lower than in patients with detected in Altaians, Khakasses, Tuvinians, and
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the less severe form of the disease. The very Shorians, groups that have a high exposure
initial stage of infection with TBEV depends on risk for TBEV in their native habitats. In
virus replication in the Langerhans cells, conclusion, these ‘TBE risk SNPs’ may even
macrophages, and neutrophils in the skin at serve as selection factors in these ethnic
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the site of tick feeding. It is worthy of groups.
speculation that the innate antiviral response,
including OAS activity, could influence the IL-28 and IL-10 polymorphisms
outcome of the infection at an early stage,
protecting some individuals from clinically The IL-28B polymorphism has been used in the
overt disease even before an adaptive era before the ‘directly acting antivirals’ (DAA)
immune response and seroconversion, very revolution to predict a sustained virological
similar to the suggestion by Lim et al. in the response (SVR) in patients chronically infected
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context of WNV infection. There are few with the hepatitis C virus (HCV). The IL- 28B
clinical data regarding TBE and mutations in polymorphism (rs12979860) is associated with
the OAS genes. In a study by Kindberg et al., an improved SVR in response to an antiviral
rs1077471 distribution was not significantly HCV regimen based on pegylated IFN,
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different between healthy controls and TBE proteinase-inhibitors, and optional ribavirin.
patients from Lithuania, although there was a Given the close genetic relationship of
non-significant tendency towards a more flaviviral pathogens like HCV and TBEV, the
frequent homozygosity for the mutant allele in role of the IL-28B and IL-10 polymorphism was
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meningoencephalitis patients (7% in TBE investigated in TBEV infections. In a study
group vs. 11% in non-TBE group) than in from the Novosibirsk region of Russia, 132 non
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healthy individuals (3%). Barkhash et al. -vaccinated patients with TBE were compared
studied 23 SNPs within the OAS gene cluster in with a regional control group comprising 221
a group of patients from Novosibirsk, healthy individuals. The results indicated that
presumably infected with the Siberian TBEV the IL-28B polymorphism (rs8103142,
subtype (TBEV-Sib), and identified 3 SNPs in rs12980275) and the IL-10 polymorphism
the OAS2 gene (rs1293762, rs15895, and (rs1800872) are genetic risk factors for TBE
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rs1732778) and 2 SNPs in OAS3 gene and in particular for severe TBE disease.
(rs2285932, rs2072136). There were
significant differences in allele and haplotype CD209 – (ICAM)-3-grabbing
frequency of these SNPs between patients non-integrin (DC-SIGN)
with mild TBEV infection (uncomplicated
meningitis and febrile disease) and with Dendritic cell (DC)-specific intercellular
encephalomeningits or myelitis. However, in adhesion molecule 3-grabbing non-integrin
contrast with other studies, 26,28 no SNPs in the (DC-SIGN) is a C-type lectin, expressed by DCs
remaining genes of the OAS cluster (OAS1 and and a subpopulation of macrophages, involved
OASL) were associated with the severity of in detection of pathogen-associated molecular

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