Page 34 - TBE_Book_V2_2019

Chapter 2a: Virology

Figure 7 thus synthesized first during translation. The
protein interacts with viral RNA genomes and
represents a structural component of the
nucleocapsid. Despite the low sequence
homology among diverse flaviviruses, regions
of hydrophobic and hydrophilic amino acids
are conserved. The C-terminal hydrophobic
domain (this domain is cleaved from mature C
protein) is preceded by a hydrophilic region,
and a central hydrophobic region. The N-
31
terminus contains a hydrophilic region. The
central hydrophobic region mediates mem-
brane association of the protein and the
charged residues that cluster at the hydro-
philic N- and C-termini presumably mediate
the interaction of the protein with viral
RNA. 39,51 In flavivirus infected cells, it was
found that the mature C protein accumulates
on the surface of endoplasmic reticulum (ER)-
derived organelles named lipid droplets. The
lipid droplets may play multiple roles during
the viral life-cycle; i.e., they could sequester
the flaviviral capsid protein early during
infection and provide a scaffold for genome
52
encapsidation.
Morphological changes in TBEV-infected
mammalian cells. 3D models of mock-infected (A) The introduction of various deletions into the
and TBEV-infected human astrocytes (B). TBEV TBEV genome that removed parts of the
infection causes extensive morphological changes, central hydrophobic domain of protein C
including membrane reorganization of the
endoplasmic reticulum; differences are evident in revealed a remarkable structural and
53
the Golgi complex, mitochondria, and phagosomes. functional flexibility of this protein. TBEV
(From Palus M, Bílý T, Elsterová J, et al. Infection mutants carrying deletions in C that extended
and injury of human astrocytes by tick-borne from residue 28 up to residue 43 were viable
encephalitis virus. J Gen Virol 2014;95(Pt 11):2411- in cell culture. The mutants produced
26, with permission). substantial amounts of subviral particles
lacking capsid, and the deletions impaired the
53
assembly or stability of the virions.
Proteins encoded by the virus However, virus viability was affected when
the deletions extended up to residue 48 or
Structural proteins
when the full hydrophobic domain was
53
C (Capsid) protein is a relatively small (11 removed. Interestingly, these deletions led
kDa), basic, and highly positively charged to spontaneous mutations in other regions of
protein with low sequence homology between the C protein that generally increased the C
39
different flaviviruses. Within the ORF that protein hydrophobicity and restored infectivity
encodes the single polyprotein precursor of all of the virus. 54
structural and non-structural proteins, protein
C is located at the amino-terminal end and is

29
29