Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication

Liu, Xiaoling; Sun, Lei; Yu, Maorong; Wang, Zengfu; Xu, Chong-Feng; Xue, Qiang; Zhang, Ke; Ye, Xin; Kitamura, Yoshihiro; Liu, Wenjun

doi:10.1111/j.1462-5822.2009.01286.x

Cited by 110 publications

(120 citation statements)

References 46 publications

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“…Similarly, the host cellular protein CyPA is also known to be involved in the replication of these viruses 16, 34, 35. It has been reported that HCMV infection induces the generation of ROS minutes after entry into the host cell 4.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Xiao¹,

Song²,

Deng³

et al. 2016

FEBS Open Bio

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Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen‐activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2‐upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose‐dependent manner. Experiments with CyPA‐specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2‐mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H2O2‐induced p38 activation, consistent with that of H2O2‐upregulated HCMV lytic replication. These results show that H2O2 is capable of activating ROS‐CyPA–p38 MAPK interactions to enhance HCMV replication.

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Section: Discussionmentioning

confidence: 99%

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Xiao¹,

Song²,

Deng³

et al. 2016

FEBS Open Bio

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“…Recently, more studies have started to reveal that CyPA can regulate biological processes independent of its PPIase activity (34,35). It was found that intracellular CyPA regulates influenza A virus infectivity through direct interaction with the virus matrix protein (M1) in a PPIase-independent manner (34).…”

Section: Discussionmentioning

confidence: 99%

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Song

Zhang

Ren³

et al. 2011

Journal of Biological Chemistry

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Cyclophilin A (CyPA) is a ubiquitously distributed peptidylprolyl cis-trans isomerase (PPIase) that possesses diverse biological functions. Extracellular CyPA is a potent chemokine, which can directly induce leukocyte chemotaxis and contribute to the pathogenesis of inflammation-mediated diseases. Although it has been identified that the chemotaxis activity of CyPA is mediated through its cell surface signaling receptor CD147, the role of CyPA PPIase activity in this process is disputable, and the underlying molecular mechanism is still poorly understood. In this study, we present the first evidence that CyPA induces leukocyte chemotaxis through a direct binding with the ectodomain of CD147 (CD147 ECT ), independent of its PPIase activity. Although NMR study indicates that the CD147 ECT

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“…Plaque assay was performed as described previously (22). Briefly, MDCK cell monolayers (0.4 ϫ 10 6 cells at 100% confluence in 12-well tissue culture plates) were washed with PBS and infected with different dilutions of virus for 1 h at 37°C.…”

Section: Cells Viruses and Antibodies Madin-darby Canine Kidney (Mmentioning

confidence: 99%

Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein

Liu

Cao

et al. 2012

J Virol

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The nuclear export of the influenza A virus ribonucleoprotein (vRNP) is crucial for virus replication. As a major component of the vRNP, nucleoprotein (NP) alone can also be shuttled out of the nucleus by interacting with chromosome region maintenance 1 (CRM1) and is therefore hypothesized to promote the nuclear export of the vRNP. In the present study, three novel nuclear export signals (NESs) of the NP-NES1, NES2, and NES3-were identified as being responsible for mediating its nuclear export. The nuclear export of NES3 was CRM1 dependent, whereas that of NES1 or NES2 was CRM1 independent. Inactivation of these NESs led to an overall nuclear accumulation of NP. Mutation of all three NP-NESs significantly impaired viral replication. Based on structures of influenza virus NP oligomers, these three hydrophobic NESs are found present on the surface of oligomeric NPs. Functional studies indicated that oligomerization is also required for nuclear export of NP. Together, these results suggest that the nuclear export of NP is important for virus replication and relies on its NESs and oligomerization.T he influenza A virus genome consists of eight negative-sense single-stranded RNA segments (vRNA) (17). Each vRNA segment is associated with multiple copies of the viral nucleoprotein (NP) and three polymerase subunits (PA, PB1, and PB2), forming the viral ribonucleoprotein (vRNP) complex. During an early stage of infection, the vRNPs are released into the cytoplasm from virions following fusion of the viral membrane and endosomal membrane (41). Subsequently, the incoming vRNPs are transported into the nucleus, where viral genome replication and transcription occur (41).One of the determinants for vRNP nuclear import is NP (8, 28, 44, 49, 52, 53), the major protein in the vRNP structure. Thus far, two nuclear localization signals (NLSs) and a nuclear accumulation signal (NAS) have been identified in NP. The stronger NLS is an unconventional signal located in the N-terminal basic region (between residues 3 and 13) of NP (28, 44), and the weaker signal, a classical bipartite NLS, is located between residues 198 and 216 (49). The NAS-spanning residues (327 to 345) were identified through analyses of mutants that lacked both of the NLSs but still exhibited partial nuclear distribution (9).At a late stage of virus infection, the vRNPs exit the nucleus to assemble and bud from the apical plasma membrane of polarized cells (3). The trafficking of the vRNPs into and out of the nucleus is a tightly regulated process (7). The nuclear export of progeny vRNPs is mediated by the CRM1 cellular export receptor (12,23,29,48). Nuclear export protein (NEP; formerly referred to as the NS2 protein), which possesses a nuclear export signal (NES), and the matrix protein (M1) of influenza A virus are deemed responsible for directing export of the vRNPs (29, 31). This process is regulated by the Raf/MEK/ERK pathway (32), which is stimulated by the membrane association of influenza virus hemagglutinin (HA) (25). Interestingly, exogenously expresse...

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Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication

Cited by 110 publications

References 46 publications

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein

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Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication

Cited by 110 publications

References 46 publications

Inhibition of cyclophilin A suppresses H2O2‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Inhibition of cyclophilin A suppresses H2O2‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein

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Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway