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2015 ; 90
(7
): 3330-41
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Subviral Hepatitis B Virus Filaments, like Infectious Viral Particles, Are
Released via Multivesicular Bodies
#MMPMID26719264
Jiang B
; Himmelsbach K
; Ren H
; Boller K
; Hildt E
J Virol
2015[Dec]; 90
(7
): 3330-41
PMID26719264
show ga
In addition to infectious viral particles, hepatitis B virus-replicating cells
secrete large amounts of subviral particles assembled by the surface proteins,
but lacking any capsid and genome. Subviral particles form spheres (22-nm
particles) and filaments. Filaments contain a much larger amount of the large
surface protein (LHBs) compared to spheres. Spheres are released via the
constitutive secretory pathway, while viral particles are ESCRT-dependently
released via multivesicular bodies (MVBs). The interaction of virions with the
ESCRT machinery is mediated by ?-taxilin that connects the viral surface protein
LHBs with the ESCRT component tsg101. Since filaments in contrast to spheres
contain a significant amount of LHBs, it is unclear whether filaments are
released like spheres or like virions. To study the release of subviral particles
in the absence of virion formation, a core-deficient HBV mutant was generated.
Confocal microscopy, immune electron microscopy of ultrathin sections and
isolation of MVBs revealed that filaments enter MVBs. Inhibition of MVB
biogenesis by the small-molecule inhibitor U18666A or inhibition of ESCRT
functionality by coexpression of transdominant negative mutants (Vps4A, Vps4B,
and CHMP3) abolishes the release of filaments while the secretion of spheres is
not affected. These data indicate that in contrast to spheres which are secreted
via the secretory pathway, filaments are released via ESCRT/MVB pathway like
infectious viral particles. IMPORTANCE: This study revises the current model
describing the release of subviral particles by showing that in contrast to
spheres, which are secreted via the secretory pathway, filaments are released via
the ESCRT/MVB pathway like infectious viral particles. These data significantly
contribute to a better understanding of the viral morphogenesis and might be
helpful for the design of novel antiviral strategies.
|Androstenes/pharmacology
[MESH]
|Cell Line, Tumor
[MESH]
|Cytoskeleton/metabolism
[MESH]
|DNA-Binding Proteins/*metabolism
[MESH]
|Endosomal Sorting Complexes Required for Transport/antagonists &
inhibitors/genetics/*metabolism
[MESH]