Syklofiliinit ja koronavirukset ? CypA.

 Tässä yhteydessä enimmäisenä mainitaan CypA


Kromosomista  7.  PPIA, CYPA, CYPH (7p13)

• CypA mainitaan usean viruksen yhteydessä.  Se tekee interaktion HIV-1 viruksen gag, Vpr ja kapsidiproteiinitekijöihin ja virus tarvitsee sitä infektoivan virioninsa muodostamiseen.

 https://www.ncbi.nlm.nih.gov/gene/5478

Official Symbol  PPIAp

Official Full Name  peptidylprolyl isomerase

Also known as CYPA; CYPH; HEL-S-69p

Summary This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [provided by RefSeq, Jul 2008]

Expression Ubiquitous expression in lymph node (RPKM 161.2), colon (RPKM 155.9) and 25 other tissues See more

Preferred Names

peptidyl-prolyl cis-trans isomerase A

Names

PPIase A

T cell cyclophilin

cyclosporin A-binding protein

epididymis secretory sperm binding protein Li 69p

peptidylprolyl isomerase A (cyclophilin A)

rotamase A 

• Proteiinissa on 105 aminohappoa.
  

  ORIGIN      
          1 mcqggdftrh ngtggksiyg ekfedenfil khtgpgilsm anagpntngs qffictakte
         61 wldgkhvvfg kvkegmnive amerfgsrng ktskkitiad cgqle
  //

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cyclophilin+E++and+coronavirus

https://www.ncbi.nlm.nih.gov/pubmed/21887220/
 Cyclophilins have been reported to play an essential role in the replication of several other RNA viruses, including human immunodeficiency virus-1, hepatitis C virus, and influenza A virus. Likewise, the replication of various nidoviruses was reported to depend on Cyps or other PPIases. This review summarizes our current understanding of this class of nidovirus-host interactions, including the potential function of in particular CypA and the inhibitory effect of Cyp inhibitors. Also the involvement of the FK-506-binding proteins and parvulins is discussed. The nidovirus data are placed in a broader perspective by summarizing the most relevant data on Cyp interactions and Cyp inhibitors for other RNA viruses.

•  Moni RNA-virus käyttää hyödykseen isäntäsolun CypA syklofiliinia. Myös nidovirusten replikaatio tarvitsee syklofiliiniA-tekijää isäntäsolusta.

Coronaviruses and arteriviruses display striking differences in their cyclophilin A-dependence during replication in cell culture.

de Wilde AH, Zevenhoven-Dobbe JC, Beugeling C, Chatterji U, de Jong D, Gallay P, Szuhai K, Posthuma CC, Snijder EJ.

Virology. 2018 Apr;517:148-156. doi: 10.1016/j.virol.2017.11.022. Epub 2017 Dec 15.Cyclophilin A (CypA) is an important host factor in the replication of a variety of RNA viruses. Also the replication of several nidoviruses was reported to depend on CypA, although possibly not to the same extent. These prior studies are difficult to compare, since different nidoviruses, cell lines and experimental set-ups were used. Here, we investigated the CypA dependence of three distantly related nidoviruses that can all replicate in Huh7 cells: the arterivirus equine arteritis virus (EAV), the alphacoronavirus human coronavirus 229E (HCoV-229E), and the betacoronavirus Middle East respiratory syndrome coronavirus (MERS-CoV). The replication of these viruses was compared in the same parental Huh7 cells and in CypA-knockout Huh7 cells generated using CRISPR/Cas9-technology. CypA depletion reduced EAV yields by ~ 3-log, whereas MERS-CoV progeny titers were modestly reduced (3-fold) and HCoV-229E replication was unchanged. This study reveals that the replication of nidoviruses can differ strikingly in its dependence on cellular CypA.

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Select item 245662233. 

•  Koronavirusreplikaatio vaatii CypA-isäntäsolutekijää . 

• SARS-koronaviruksessa syklofiliinit tunnistetaan pan-koronavirusinhibiittorien kohdemolekyyleinä.

Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir.

Carbajo-Lozoya J, Ma-Lauer Y, Malešević M, Theuerkorn M, Kahlert V, Prell E, von Brunn B, Muth D, Baumert TF, Drosten C, Fischer G, von Brunn A.

Virus Res. 2014 May 12;184:44-53. doi: 10.1016/j.virusres.2014.02.010. Epub 2014 Feb 22 The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches..

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