Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a trans-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion

Cited 21 time in webofscience Cited 0 time in scopus
  • Hit : 372
  • Download : 58
The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins. IMPORTANCE The mechanisms by which infectious hepatitis C virus particles are assembled and released from the cell are poorly understood. We show that the virus subverts host cell trafficking pathways to effect the release of virus particles and disrupts the structure of the Golgi apparatus, a key cellular organelle involved in secretion. In addition, we demonstrate that the mechanisms used by the virus to exit the cell are distinct from those used by the cell to release lipoproteins, suggesting that the virus effects a unique modification to cellular trafficking pathways
Publisher
AMER SOC MICROBIOLOGY
Issue Date
2016-08
Language
English
Article Type
Article
Keywords

NONSTRUCTURAL PROTEIN 5A; CORE PROTEIN; LIPID DROPLETS; FUNCTIONAL-CHARACTERIZATION; RNA REPLICATION; NS2 PROTEIN; PARTICLES; TRAFFICKING; DETERMINANTS; TRANSMISSION

Citation

JOURNAL OF VIROLOGY, v.90, no.16, pp.7159 - 7170

ISSN
0022-538X
DOI
10.1128/JVI.00826-16
URI
http://hdl.handle.net/10203/213160
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
96967.pdf(4.23 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 21 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0