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Items: 12
1. Gammacoronavirus, Igacovirus , Avian IBV
Vasfi Marandi M, Malekan M, Ranjbar MM, Dadashpour Davachi N, Alamian S.
Arch Razi Inst. 2018 Sep;73(3):183-198. doi: 10.22092/ari.2018.120305.1192. Epub 2018 Sep 1.
- PMID:
- 30280838
2.
Liu G, Wang Y, Anderson GJ, Camaschella C, Chang Y, Nie G.
J Cell Biochem. 2016 Jan;117(1):207-17. doi: 10.1002/jcb.25267.
- PMID:
- 26100117
3.
Debray
FG, Stümpfig C, Vanlander AV, Dideberg V, Josse C, Caberg JH, Boemer F,
Bours V, Stevens R, Seneca S, Smet J, Lill R, van Coster R.
J Inherit Metab Dis. 2015 Nov;38(6):1147-53. doi: 10.1007/s10545-015-9857-1. Epub 2015 May 14.
- PMID:
- 25971455
4.Alphacoronavirus TGEV
Gelhaus S, Thaa B, Eschke K, Veit M, Schwegmann-Weßels C.
Virology. 2014 Sep;464-465:397-405. doi: 10.1016/j.virol.2014.07.035. Epub 2014 Aug 9 Abstract
The spike protein S of coronaviruses
contains a highly conserved cytoplasmic cysteine-rich motif adjacent to
the transmembrane region. This motif is palmitoylated in the
Betacoronaviruses MHV and SARS-CoV. Here, we demonstrate by metabolic
labeling with [(3)H]-palmitic acid that the S protein of transmissible
gastroenteritis coronavirus (TGEV), an Alphacoronavirus, is
palmitoylated as well. This is relevant for TGEV replication as virus
growth was compromised by the general palmitoylation
inhibitor 2-bromopalmitate. Mutation of individual cysteine clusters in
the cysteine-rich motif of S revealed that all cysteines must be
replaced to abolish acylation and incorporation of S into virus-like
particles (VLP). Conversely, the interaction of S with the M protein,
essential for VLP incorporation of S, was not impaired by lack of palmitoylation. Thus, palmitoylation of the S protein of Alphacoronaviruses is dispensable for S-M interaction, but required for the generation of progeny virions.- PMID:
- 25113909
5.
Yang J, Lv J, Wang Y, Gao S, Yao Q, Qu D, Ye R.
Virology. 2012 Jun 5;427(2):98-106. doi: 10.1016/j.virol.2012.02.015. Epub 2012 Mar 15.
A conserved cysteine-rich motif located between the transmembrane domain
and the endodomain is essential for membrane fusion and assembly of
coronavirus spike (S) protein. Here, we proved that three cysteines
within the motif, but not dependent on position, are minimally required
for the survival of the recombinant mouse hepatitis virus. When the
carboxy termini with these mutated motifs of S proteins were
respectively introduced into a heterogeneous protein, both incorporation
into lipid rafts and S-palmitoylation
of these recombinant proteins showed a similar quantity requirement to
cysteine residues. Meanwhile, the redistribution of these proteins on
cellular surface indicated that the absence of the positively charged
rather than cysteine residues in the motif might lead the dramatic
reduction in syncytial formation of some mutants with the deleted
motifs. These results suggest that multiple cysteine as well as charged
residues concurrently improves the membrane-associated functions of S
protein in viral replication and cytopathogenesis.Free PMC Article
6.
McBride CE, Machamer CE.
Virology. 2010 Sep 15;405(1):139-48. doi: 10.1016/j.virol.2010.05.031. Epub 2010 Jul 1.Coronaviruses are enveloped RNA viruses that generally cause mild
disease in humans. However, the recently emerged coronavirus that caused
severe acute respiratory syndrome (SARS-CoV) is the most pathogenic
human coronavirus discovered to date. The SARS-CoV spike (S) protein
mediates virus entry by binding cellular receptors and inducing fusion
between the viral envelope and the host cell membrane. Coronavirus S
proteins are palmitoylated, which may affect function. Here, we created a
non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic
cysteine residues. Palmitoylation
of SARS-CoV S was required for partitioning into detergent-resistant
membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation
of mouse hepatitis virus S protein for interaction with M protein and
may point to important differences in assembly and infectivity of these
two coronaviruses.
7.
Shulla A, Gallagher T.
J Biol Chem. 2009 Nov 20;284(47):32725-34. doi: 10.1074/jbc.M109.043547. Epub 2009 Sep 30. Abstract
Enveloped viruses
enter cells by viral glycoprotein-mediated binding to host cells and
subsequent fusion of virus and host cell membranes. For the
coronaviruses, viral spike (S) proteins execute these cell entry
functions. The S proteins are set apart from other viral and cellular
membrane fusion proteins by their extensively palmitoylated
membrane-associated tails. Palmitate adducts are generally required for
protein-mediated fusions, but their precise roles in the process are
unclear. To obtain additional insights into the S-mediated membrane
fusion process, we focused on these acylated carboxyl-terminal
intravirion tails. Substituting alanines for the cysteines that are
subject to palmitoylation
had effects on both S incorporation into virions and S-mediated
membrane fusions. In specifically dissecting the effects of endodomain
mutations on the fusion process, we used antiviral heptad repeat
peptides that bind only to folding intermediates in the S-mediated
fusion process and found that mutants lacking three palmitoylated
cysteines remained in transitional folding states nearly 10 times longer
than native S proteins. This slower refolding was also reflected in the
paucity of postfusion six-helix bundle configurations among the mutant S
proteins. Viruses with fewer palmitoylated S protein cysteines entered
cells slowly and had reduced specific infectivities. These findings
indicate that lipid adducts anchoring S proteins into virus membranes
are necessary for the rapid, productive S protein refolding events that
culminate in membrane fusions. These studies reveal a previously
unappreciated role for covalently attached lipids on the endodomains of
viral proteins eliciting membrane fusion reactions.
- PMID:
- 19801669
- PMCID:
- PMC2781689
- DOI:
- 10.1074/jbc.M109.043547
8.
Akerström S, Gunalan V, Keng CT, Tan YJ, Mirazimi A.
Virology. 2009 Dec 5;395(1):1-9. doi: 10.1016/j.virol.2009.09.007. Epub 2009 Oct 1.
Nitric oxide is an important molecule playing a key role in a broad
range of biological process such as neurotransmission, vasodilatation
and immune responses. While the anti-microbiological properties of
nitric oxide-derived reactive nitrogen intermediates (RNI) such as
peroxynitrite, are known, the mechanism of these effects are as yet
poorly studied. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)
belongs to the family Coronaviridae, was first identified during
2002-2003. Mortality in SARS patients ranges from between 6 to 55%. We
have previously shown that nitric oxide inhibits the replication cycle
of SARS-CoV in vitro by an unknown mechanism. In this study, we have
further investigated the mechanism of the inhibition process of nitric
oxide against SARS-CoV. We found that peroxynitrite, an intermediate
product of nitric oxide in solution formed by the reaction of NO with
superoxide, has no effect on the replication cycle of SARS-CoV,
suggesting that the inhibition is either directly effected by NO or a
derivative other than peroxynitrite. Most interestingly, we found that
NO inhibits the replication of SARS-CoV by two distinct mechanisms.
Firstly, NO or its derivatives cause a reduction in the palmitoylation
of nascently expressed spike (S) protein which affects the fusion
between the S protein and its cognate receptor, angiotensin converting
enzyme 2. Secondly, NO or its derivatives cause a reduction in viral RNA
production in the early steps of viral replication, and this could
possibly be due to an effect on one or both of the cysteine proteases
encoded in Orf1a of SARS-CoVFree PMC Article
9.
Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA, Dias JA.
Mol Cell Endocrinol. 2007 Jan 2;260-262:153-62. Epub 2006 Oct 12.
- PMID:
- 17045734
10.
Thorp EB, Boscarino JA, Logan HL, Goletz JT, Gallagher TM.
J Virol. 2006 Feb;80(3):1280-9.
Coronavirus spike (S) proteins are palmitoylated at several cysteine
residues clustered near their transmembrane-spanning domains. This is
achieved by cellular palmitoyl acyltransferases (PATs), which can modify
newly synthesized S proteins before they are assembled into virion
envelopes at the intermediate compartment of the exocytic pathway. To
address the importance of these fatty acylations to coronavirus
infection, we exposed infected cells to 2-bromopalmitate (2-BP), a
specific PAT inhibitor. 2-BP profoundly reduced the specific
infectivities of murine coronaviruses at very low, nontoxic doses that
were inert to alphavirus and rhabdovirus infections. 2-BP effected only
two- to fivefold reductions in S palmitoylation,
yet this correlated with reduced S complexing with virion membrane (M)
proteins and consequent exclusion of S from virions. At defined 2-BP
doses, underpalmitoylated S proteins instead trafficked to infected cell
surfaces and elicited cell-cell membrane fusions, suggesting that the
acyl chain adducts are more critical to virion assembly than to
S-induced syncytial developments. These studies involving pharmacologic
inhibition of S protein palmitoylation
were complemented with molecular genetic analyses in which cysteine
acylation substrates were mutated. Notably, some mutations (C1347F and
C1348S) did not interfere with S incorporation into virions, indicating
that only a subset of the cysteine-rich region provides the essential
S-assembly functions. However, the C1347F/C1348S mutant viruses
exhibited relatively low specific infectivities, similar to virions
secreted from 2-BP-treated cultures. Our collective results indicate
that the palmitate adducts on coronavirus S proteins are necessary in
assembly and also in positioning the assembled envelope proteins for
maximal infectivity.Free PMC Article
12.
Veit M, Sachs K, Heckelmann M, Maretzki D, Hofmann KP, Schmidt MF.
Biochim Biophys Acta. 1998 Oct 2;1394(1):90-8. Erratum in: Biochim Biophys Acta 1999 Jan 4;1436(3):630.
- PMID:
- 9767130
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