PMID- 24721789
OWN - NLM
STAT- MEDLINE
DCOM- 20141121
LR  - 20211021
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 6
IP  - 4
DP  - 2014 Apr 9
TI  - Analysis of determinants in filovirus glycoproteins required for tetherin 
      antagonism.
PG  - 1654-71
LID - 10.3390/v6041654 [doi]
AB  - The host cell protein tetherin can restrict the release of enveloped viruses from 
      infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from 
      the site of viral budding, the plasma membrane, and this process depends on 
      specific interactions between the transmembrane domains of Vpu and tetherin. In 
      contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, 
      antagonize tetherin without reducing surface expression, and the domains in GP 
      required for tetherin counteraction are unknown. Here, we show that filovirus GPs 
      depend on the presence of their authentic transmembrane domains for virus-cell 
      fusion and tetherin antagonism. However, conserved residues within the 
      transmembrane domain were dispensable for membrane fusion and tetherin 
      counteraction. Moreover, the insertion of the transmembrane domain into a 
      heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin 
      antagonism to the recipient. Finally, mutation of conserved residues within the 
      fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate 
      tetherin counteraction, indicating that the fusion peptide and the ability of GP 
      to drive host cell entry are not required for tetherin counteraction. These 
      results suggest that the transmembrane domains of filoviral GPs contribute to 
      tetherin antagonism but are not the sole determinants.
FAU - Gnirss, Kerstin
AU  - Gnirss K
AD  - Infection Biology Unit, German Primate Center, 37077 Gottingen, Germany. 
      KGnirss@dpz.eu.
FAU - Fiedler, Marie
AU  - Fiedler M
AD  - Infection Biology Unit, German Primate Center, 37077 Gottingen, Germany. 
      MFiedler@dpz.eu.
FAU - Kramer-Kuhl, Annika
AU  - Kramer-Kuhl A
AD  - Infection Biology Unit, German Primate Center, 37077 Gottingen, Germany. 
      annika.kraemer-kuehl@boehringer-ingelheim.com.
FAU - Bolduan, Sebastian
AU  - Bolduan S
AD  - Institute of Virology, Helmholtz Center Munich, 85764 Neuherberg, Germany. 
      sebastian.bolduan@helmholtz-muenchen.de.
FAU - Mittler, Eva
AU  - Mittler E
AD  - Institute of Virology, Philipps-University-Marburg, 35043 Marburg, Germany. 
      mittlere@staff.uni-marburg.de.
FAU - Becker, Stephan
AU  - Becker S
AD  - Institute of Virology, Philipps-University-Marburg, 35043 Marburg, Germany. 
      becker@staff.uni-marburg.de.
FAU - Schindler, Michael
AU  - Schindler M
AD  - Institute of Virology, Helmholtz Center Munich, 85764 Neuherberg, Germany. 
      michael.schindler@helmholtz-muenchen.de.
FAU - Pohlmann, Stefan
AU  - Pohlmann S
AD  - Infection Biology Unit, German Primate Center, 37077 Gottingen, Germany. 
      spoehlmann@dpz.eu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140409
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Antigens, CD)
RN  - 0 (BST2 protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Antigens, CD
MH  - Cell Line
MH  - DNA Mutational Analysis
MH  - Ebolavirus/genetics/*physiology
MH  - GPI-Linked Proteins/antagonists & inhibitors
MH  - Glycoproteins/genetics/*metabolism
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Marburgvirus/genetics/*physiology
MH  - Viral Proteins/genetics/*metabolism
PMC - PMC4014715
EDAT- 2014/04/12 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/04/01
CRDT- 2014/04/12 06:00
PHST- 2013/11/25 00:00 [received]
PHST- 2014/03/27 00:00 [revised]
PHST- 2014/03/30 00:00 [accepted]
PHST- 2014/04/12 06:00 [entrez]
PHST- 2014/04/12 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - v6041654 [pii]
AID - viruses-06-01654 [pii]
AID - 10.3390/v6041654 [doi]
PST - epublish
SO  - Viruses. 2014 Apr 9;6(4):1654-71. doi: 10.3390/v6041654.