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Chapter 2a



                                       Virology




                   Daniel Růžek, Kentaro Yoshii, Marshall E. Bloom

                                      and Ernest A. Gould


          Key Points


           •  TBEV is the most medically important member of the tick-borne serocomplex group
             within the genus Flavivirus, family Flaviviridae.

           •  Three antigenic subtypes of TBEV correspond to the 3 recognized genotypes: European
             (TBEV-EU), also known as Western, Far Eastern (TBEV-FE), and Siberian (TBEV-SIB).
             Additional 2 genotypes have been identified in the Irkutsk region of Russia, currently named
             TBE virus Baikalian subtype (TBEV-BKL) and TBE virus Himalaya subtype (Himalayan and “178-
             79” group; TBEV-HIM).
           •  TBEV virions are small enveloped spherical particles about 50 nm in diameter.

           •  The TBEV genome consists of a single-stranded positive sense RNA molecule.
           •  The genome encodes one open reading frame (ORF), which is flanked by untranslated
             (non-coding) regions (UTRs).
           •  The 5′-UTR end has a methylated nucleotide cap for canonical cellular translation. The 3′-UTR
             is not polyadenylated and is characterized by extensive length and sequence heterogeneity.
           •  The ORF encodes one large polyprotein, which is  co- and post-translationally cleaved into 3
             structural proteins (C, prM, and E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A,
             NS4B, and NS5).
           •  TBEV replicates in the cytoplasm of the host cell in close association with virus-induced
             intracellular membrane structures. Virus assembly occurs in the endoplasmic reticulum.
             The immature virions are transported to the Golgi complex, and mature virions pass through
             the host secretory pathway and are finally released from the host cell by fusion of the transport
             vesicle membrane with the plasma membrane.

          Virus classification

          Tick-borne  encephalitis  virus  (TBEV)  is  the   The genus Flavivirus comprises over 70 virus
          most  medically  important  member  of  the   species, many of which are important human
                                                               1
          tick-borne  serocomplex  group  within  the   pathogens.   Besides  TBEV,  these  include
          genus Flavivirus, family Flaviviridae (from the   mosquito-borne  viruses  such  as  dengue
          Latin  flavus  –  ‘yellow’,  referring  to  the   viruses,  Japanese  encephalitis  virus,  yellow
          prototype virus, yellow fever virus).       fever  virus,  Zika  virus,  and  many  others.
                                                      Virtually  the  entire  human  population  lives



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