Page 112 - TBE_Book_V2_2019

Chapter 5: TBE in adults

concluded that a fatal outcome of TBE may be WNV outbreak. In conclusion, the CCR5Δ32
a consequence of coexisting risk factors, such mutation is a strong predictor for a severe
as old age and chronic underlying diseases. clinical course of WNV infections in the human
Special efforts should be made to vaccinate host. Following the epidemiological results
elderly people (>50 years of age), who from WNV research, a potential effect of the
constitute the main group at risk for develop- CCR5Δ32 mutation on TBE was investigated. A
ment of severe courses of TBE and long-term clinical study from Lithuania analyzed the
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sequelae. incidence of the CCR5Δ32 mutation in
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different patient populations. In adult
Host genetic risk factors patients with TBE, 2.3% (n=129) of patients
were homozygous for CCR5Δ32. Control
As mentioned above, clinical and patients with aseptic meningitis (n=76), and a
epidemiological data indicate that human second healthy control group (n=134),
susceptibility to clinical TBEV infection greatly included no patients with a homozygote
varies according to age, gender, and ethnicity. CCR5Δ32 mutation. A second study with adult
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The potential role of a genetic background for and pediatric TBE patients enrolled 246
TBE was investigated in mouse models, where patients in total (n=117 pediatric, n=129
different mouse strains differ greatly in adult). There were 2 control groups: 1 with 79
susceptibility, virus replication rate, and patients with aseptic meningitis and a second
characteristics of the immune/inflammatory with 135 healthy individuals. Patients with TBE
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response. Most of the genetic factors were stratified into subgroups on the basis of
analyzed are part of the innate immune clinical parameters and severity of disease. It
response of the mammalian host to TBEV. A was shown that, in the TBE patients, a
selection of genetic predispositions is homozygote CCR5Δ32 mutation was detected
discussed in the following section in the with significantly greater frequency than in
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context of TBE. the control populations, but there was no
correlation between disease severity and
C-C chemokine receptor type 5 (CCR5) CCR5Δ32 mutational status. Mutations in
another C-C chemokine receptor, CCR2, are
The CCR5 plays a key role in leukocyte linked to a slower progression of HIV
migration and attraction. In human infections; however, any association between
immunodeficiency virus (HIV) infections, the
CCR2 and TBE has not yet been studied.
CCR5Δ32 mutation is important for the
invasion of CD4 cells by HIV particles with a Toll-like receptor 3
CCR5 tropism. Based on these findings, the
CCR5 entry inhibitor, mavaviroc, was Toll-like receptor 3 (TLR 3) is an intracellular
successfully introduced into clinical use in pattern recognition receptor (PRR), active
2007. In mouse models for flaviral infections, within the cell and located to a lesser degree
it had been demonstrated that homozygote at the cell surface, which recognizes double-
CCR5-deficient (-/-) mice died in almost 100% stranded ribonucleic acid (dsRNA), thus
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of all infections with West Nile virus (WNV) ; making it an important factor in the innate
whereas CCR5 (-/+) heterozygote mice, and response to most viruses. 14,15 Activation of
homozygote mice with a wildtype CCR5 TLR3 results in activation of the NFκB pro-
receptor, had a significantly lower mortality inflammatory transcription factor pathway,
rate after WNV infection. These data from and synthesis of type 1 and type 3 interferon
animal studies were later confirmed in a (IFN). 14,16 TLR3-dependent signaling has been
cohort study from North America during a described in different cell types, including

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