Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected.
Identifieur interne : 002B34 ( Main/Exploration ); précédent : 002B33; suivant : 002B35Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected.
Auteurs : Sara Akerström [Suède] ; Vithiagaran Gunalan ; Choong Tat Keng ; Yee-Joo Tan ; Ali MirazimiSource :
- Virology [ 1096-0341 ] ; 2009.
Descripteurs français
- KwdFr :
- ARN viral (), ARN viral (biosynthèse), Acide peroxynitreux (pharmacologie), Animaux, Cellules Vero, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (métabolisme), Humains, Lipoylation, Monoxyde d'azote (pharmacologie), Protéines de l'enveloppe virale (métabolisme), Réplication virale, Virus du SRAS (), Virus du SRAS (physiologie).
- MESH :
- biosynthèse : ARN viral.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- pharmacologie : Acide peroxynitreux, Monoxyde d'azote.
- physiologie : Virus du SRAS.
- ARN viral, Animaux, Cellules Vero, Glycoprotéine de spicule des coronavirus, Humains, Lipoylation, Réplication virale, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Chlorocebus aethiops, Humans, Lipoylation, Membrane Glycoproteins (metabolism), Nitric Oxide (pharmacology), Peroxynitrous Acid (pharmacology), RNA, Viral (biosynthesis), RNA, Viral (drug effects), SARS Virus (drug effects), SARS Virus (physiology), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (metabolism), Virus Replication.
- MESH :
- chemical , biosynthesis : RNA, Viral.
- chemical , drug effects : RNA, Viral.
- chemical , metabolism : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , pharmacology : Nitric Oxide, Peroxynitrous Acid.
- drug effects : SARS Virus.
- physiology : SARS Virus.
- Animals, Chlorocebus aethiops, Humans, Lipoylation, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Replication.
Abstract
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-CoV.
DOI: 10.1016/j.virol.2009.09.007
PubMed: 19800091
Affiliations:
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Le document en format XML
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()</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Nitric Oxide</term><term>Peroxynitrous Acid</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acide peroxynitreux</term><term>Monoxyde d'azote</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Lipoylation</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN viral</term><term>Animaux</term><term>Cellules Vero</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Lipoylation</term><term>Réplication virale</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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-CoV.</div></front></TEI><affiliations><list><country><li>Suède</li></country></list><tree><noCountry><name sortKey="Gunalan, Vithiagaran" sort="Gunalan, Vithiagaran" uniqKey="Gunalan V" first="Vithiagaran" last="Gunalan">Vithiagaran Gunalan</name><name sortKey="Keng, Choong Tat" sort="Keng, Choong Tat" uniqKey="Keng C" first="Choong Tat" last="Keng">Choong Tat Keng</name><name sortKey="Mirazimi, Ali" sort="Mirazimi, Ali" uniqKey="Mirazimi A" first="Ali" last="Mirazimi">Ali Mirazimi</name><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name></noCountry><country name="Suède"><noRegion><name sortKey="Akerstrom, Sara" sort="Akerstrom, Sara" uniqKey="Akerstrom S" first="Sara" last="Akerström">Sara Akerström</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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