CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A

Pushkarsky, Tatiana; Zybarth, Gabriele; Dubrovsky, Larisa; Yurchenko, Vyacheslav; Tang, Hao; Guo, Huiming; Toole, Bryan P.; Sherry, Barbara; Bukrinsky, Michael

doi:10.1073/pnas.111583198

Cited by 249 publications

(244 citation statements)

References 46 publications

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“…Moreover, functioning as a receptor for cyclophilin A makes CD147 a facilitator of HIV-1 infection (Pushkarsky et al 2001). This property derives from the ability of HIV-1 to incorporate cyclophilin A into virions, a feature which is common to other viruses (Castro et al 2003;Lin and Emerman 2006).…”

Section: Bsg (Ok System)mentioning

confidence: 99%

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

Fumagalli¹,

Cagliani²,

Pozzoli³

et al. 2008

Genome Res.

153

141

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Historically, allelic variations in blood group antigen (BGA) genes have been regarded as possible susceptibility factors for infectious diseases. Since host-pathogen interactions are major determinants in evolution, BGAs can be thought of as selection targets. In order to verify this hypothesis, we obtained an estimate of pathogen richness for geographic locations corresponding to 52 populations distributed worldwide; after correction for multiple tests and for variables different from selective forces, significant correlations with pathogen richness were obtained for multiple variants at 11 BGA loci out of 26. In line with this finding, we demonstrate that three BGA genes, namely CD55, CD151, and SLC14A1, have been subjected to balancing selection, a process, rare outside MHC genes, which maintains variability at a locus. Moreover, we identified a gene region immediately upstream the transcription start site of FUT2 which has undergone non-neutral evolution independently from the coding region. Finally, in the case of BSG, we describe the presence of a highly divergent haplotype clade and the possible reasons for its maintenance, including frequency-dependent balancing selection, are discussed. These data indicate that BGAs have been playing a central role in the host-pathogen arms race during human evolutionary history and no other gene category shows similar levels of widespread selection, with the only exception of loci involved in antigen recognition.

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Section: Bsg (Ok System)mentioning

confidence: 99%

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

Fumagalli¹,

Cagliani²,

Pozzoli³

et al. 2008

Genome Res.

153

141

View full text Add to dashboard Cite

show abstract

“…9 Furthermore, EMMPRIN has been reported to be involved in immune cell activation, 10,11 in processes mediating viral entry into cells, 12 in cell-cell interactions in the developing nervous system, 13 in blood-brain barrier development 14,15 or in cyclophilin function. 16 Moreover, EMM-PRIN knockout mice are often sterile or present with deficiencies in spermatogenesis and fertilization.…”

mentioning

confidence: 99%

High incidence of EMMPRIN expression in human tumors

Riethdorf

Reimers

Assmann

et al. 2006

Intl Journal of Cancer

206

172

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Extracellular matrix metalloproteinase inducer expressed by tumor cells stimulates peritumoral fibroblasts to produce matrix metalloproteinases, thus contributing to tumor invasion and metastasis. To assess its suitability as potential therapeutic target, the overall incidence of EMMPRIN expression in normal and neoplastic tissues was analyzed. EMMPRIN expression was detected immunohistochemically using monoclonal antibodies MEM-M6/1 and HIM6 and tissue microarrays with 2,348 and 608 tissue samples from 129 distinct tumor types and 76 different normal tissues, respectively. Expression and glycosylation state of EMMPRIN in human breast cancer cells were analyzed by Western blot analysis with monoclonal antibodies recognizing distinct carbohydrate structures and biochemical methods. EMMPRIN expression was found in 112 of 129 tumor entities analyzed with malignant tumors being EMMPRIN positive more frequently than benign tumors. A remarkable heterogeneity in EMMPRIN expression between tumor entities was observed. Among others, squamous-cell carcinomas (60-100%), pancreatic (87%), chromophobic kidney (83%), hepatocellular (83%) or medullary breast (83%) adenocarcinomas as well as glioblastoma multiforme (79%) presented with a particular high incidence of EMMPRIN expression. There were a limited number of EMMPRIN-positive normal cell types including proliferatively active and differentiating epithelial cells, germ cells, myocardial cells in the left heart ventricle or vascular endothelial cells of the brain. We could further demonstrate that breast cancer cells expressed EMMPRIN isoforms differing in the presence or absence of Lewis X glycan structures. Our results may assist in defining the suitability of EMMPRIN as therapeutic target and predicting negative side effects. ' 2006 Wiley-Liss, Inc.Key words: extracellular matrix metalloproteinase inducer expression; human normal tissues; human tumors; glycosylation Tumor cell invasion and metastasis requires degradation of extracellular matrix components, which is mainly achieved by various proteolytic enzymes including zinc-dependent matrix metalloproteinases (MMPs). Analysis of MMP expression patterns in tumor specimens revealed that the majority of these enzymes are produced by stromal cells surrounding the tumor rather than by tumor cells themselves. An increasing body of evidence, however, suggests that MMP synthesis is stimulated by tumor cells in a paracrine fashion. This stimulation is at least partially attributed to extracellular matrix metalloproteinase inducer (EMMPRIN, also designated CD147 or basigin), a 58 kDa surface glycoprotein of the immunoglobulin superfamily, originally purified from the plasma membrane of cancer cells. 1 EMMPRIN has been demonstrated to stimulate production of MMP-1, -2, -3, -9, -14, -15 in fibroblasts surrounding tumor cells. 2 As shown by Sun and Hemler, 3 EMMPRIN also appears to participate in the induction of MMP production in tumor cells in an autocrine fashion. Accordingly, MDA-MB-436 human breast cancer cells recombinantly...

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“…We investigated activity of this mutant using a previously described approach which relies on infection of CD147-transfected CHO cells with HIV-1 construct pseudotyped with an amphotropic MuLV envelope [13]. Such pseudotyped virus is going through a one-cycle replication in CHO cells.…”

Section: Signaling Is Not Required For Cd147-mediated Enhancement Ofmentioning

confidence: 99%

“…Such pseudotyped virus is going through a one-cycle replication in CHO cells. Importantly, this approach has been previously validated as an unbiased test for CypA-CD147 interactions [13].…”

Section: Signaling Is Not Required For Cd147-mediated Enhancement Ofmentioning

confidence: 99%

“…Biochemical studies indicate that CypA is exposed on the viral surface [23;24] and thus may signal through CD147. CD147 has been shown also to stimulate, in a CypA-dependent manner, an early step of HIV-1 replication [13], however, the role of signaling events in this activity of CD147 has not been investigated. In this report, we provide evidence that signaling from CD147 is not required for its activity in HIV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

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CD147 stimulates HIV-1 infection in a signal-independent fashion

Pushkarsky

Yurchenko

Laborico

et al. 2007

Biochemical and Biophysical Research Communications

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CD147 is a type I transmembrane protein previously identified as a signal transducing receptor for extracellular cyclophilins. CD147-expressing cells exhibit a characteristic activation of extracellularsignal regulated kinase 1 and 2 (ERK1/2) in response to stimulation with cyclophilin A (CypA). CD147 was also shown to enhance HIV-1 infection in a CypA-dependent fashion, but the role of signaling in this activity of CD147 has not been investigated. In this report, we demonstrate that neither mutations incapacitating signaling response of CD147 to CypA stimulation, nor inhibitor of ERK activation, reduced susceptibility of cells to HIV-1 infection. Surprisingly, truncation of the cytoplasmic tail of CD147 did not abolish signaling response to CypA, but reduced infection by HIV-1 to the level observed in control cells. These results indicate that CD147 enhances HIV-1 replication in a signaling-independent fashion through specific events mediated by the cytoplasmic domain of the protein.

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CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A

Cited by 249 publications

References 46 publications

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

High incidence of EMMPRIN expression in human tumors

CD147 stimulates HIV-1 infection in a signal-independent fashion

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