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

Pushkarsky, Tatiana; Yurchenko, Vyacheslav; Laborico, Alicia; Bukrinsky, Michael

doi:10.1016/j.bbrc.2007.08.192

Cited by 29 publications

(28 citation statements)

References 32 publications

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“…Overall, the over-expression of CypB significantly enhanced infection at a magnitude comparable to other HIV cell factors (Hoque et al, 2011; Maddon et al, 1986; Pushkarsky et al, 2007), and the effect occurred in the presence of endogenous CypB. Unfortunately, we were unable to assess the necessity of CypB for HIV infection as we could not knock-down CypB in 293T cells without cytopathic effects ( data not shown ).…”

Section: Discussionmentioning

confidence: 93%

Cyclophilin B enhances HIV-1 infection

2016

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Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import.

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Section: Discussionmentioning

confidence: 93%

Cyclophilin B enhances HIV-1 infection

2016

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“…However, CD147 is not known to mediate signal transduction events, suggesting that other molecule(s) associated with CD147 may function as a signal-transducing co-receptor. Consistent with this notion, truncation of the cytoplasmic tail of CD147 does not abolish signalling response to eCypA [10]. The possibility of additional co-receptor is also supported by inability of eosinophils to respond to eCypA despite the fact that these cells express relatively high levels of CD147 [5].…”

Section: Introductionmentioning

confidence: 91%

The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

et al. 2011

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BackgroundPrevious studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.ResultsHere, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.ConclusionsOur results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

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“…Virus-associated CyPA binds to CD147 on host cells, a step necessary for HIV-1 infection [19]. However, this infection happens in a signalling-independent fashion and is not affected by inhibition of downstream signalling molecules like Erk [20]. Similarly as for CyPA, stimulation with CyPB leads to activation of Erk as well as protein kinase C-d, chemotaxis and cell adhesion.…”

Section: Cd147mentioning

confidence: 97%