The Ezrin-Radixin-Moesin Family Member Ezrin Regulates Stable Microtubule Formation and Retroviral Infection

Haedicke, Juliane; Santos, Kenia de los; Goff, Stephen P.; Naghavi, Mojgan H.

doi:10.1128/jvi.02403-07

Cited by 50 publications

(53 citation statements)

References 39 publications

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“…It has recently been described that moesin and ezrin limit HIV-1 viral replication by affecting tubulin cytoskeleton at a post-entry step (Haedicke et al, 2008;Naghavi et al, 2007). Strikingly, in that study, dominant-negative N-moesin was equally as effective as the functional full-length protein at blocking viral replication, which apparently contradicts previous knowledge about how these proteins exert their function.…”

Section: Discussioncontrasting

confidence: 56%

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Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes

Barrero-Villar

Cabrero

Gordon-Alonso

et al. 2009

Journal of Cell Science

115

223

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The human immunodeficiency virus 1 (HIV-1) envelope regulates the initial attachment of viral particles to target cells through its association with CD4 and either CXCR4 or CCR5. Although F-actin is required for CD4 and CXCR4 redistribution, little is known about the molecular mechanisms underlying this fundamental process in HIV infection. Using CD4+ CXCR4+ permissive human leukemic CEM T cells and primary lymphocytes, we have investigated whether HIV-1 Env might promote viral entry and infection by activating ERM (ezrin-radixin-moesin) proteins to regulate F-actin reorganization and CD4/CXCR4 co-clustering. The interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation. Moreover, the association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane. Suppression of moesin expression with dominant-negative N-moesin or specific moesin silencing impedes reorganization of F-actin and HIV-1 entry and infection mediated by the HIV-1 envelope protein complex. Therefore, we propose that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes.

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Section: Discussioncontrasting

confidence: 56%

“…Recently, ezrin has been shown to have a tubulin-dependent role in HIV-1 infection (Haedicke et al, 2008). ERM proteins seem to exert pleiotropic effects on HIV-1 infection, which are dependent of the tropism of the HIV-1 viral strain (Kubo et al, 2008).…”

Section: The Human Immunodeficiency Virus 1 (Hiv-1) Envelope Regulatementioning

confidence: 99%

Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes

Barrero-Villar

Cabrero

Gordon-Alonso

et al. 2009

Journal of Cell Science

115

223

View full text Add to dashboard Cite

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“…For example, although expression of APOBEC3G in neurons contributes to the restriction of HIV-1, it is present in many cells types and as such, its' expression alone does not explain the high degree of resistance observed in neurons (10,12). The discovery of restriction factors such as TRIMs and APOBECs, whose sole function to date appears to be to inhibit virus replication (28), along with antiviral factors, whose presence or absence within the host cell alters virus replication (14,(32)(33)(34)(35)(36)(37) have highlighted the complexity of mechanisms that govern cellular susceptibility to retroviral infection. Many of these factors are expressed in a wide range of tissues and their expression is increased in response to IFN, suggesting that they function as part of the hosts' antiviral response mechanism (28,29).…”

Section: Resultsmentioning

confidence: 99%

The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection

Haedicke

Brown

Naghavi

2009

Proc. Natl. Acad. Sci. U.S.A.

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Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-1), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-1 infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1.

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“…For instance, the human immunodeficiency virus 1 (HIV-1) capsid protein p24 interacts with dynein and facilitates trafficking movement of HIV-1 capsids to the perinuclear region or MT-organizing centre (MTOC) [63]. Decreasing MT stability by overexpression of the ezrin-radixinmoesin family members, such as ezrin and moesin, significantly reduces HIV-1 infection at a step prior to reverse transcription [64].…”

Section: Modulating Mt To Inhibit Viral Infectionmentioning

confidence: 99%

Cellular defence or viral assist: the dilemma of HDAC6

Zheng

Jiang

et al. 2017

Journal of General Virology

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Histone deacetylase 6 (HDAC6) is a unique cytoplasmic deacetylase that regulates various important biological processes by preventing protein aggregation and deacetylating different non-histone substrates including tubulin, heat shock protein 90, cortactin, retinoic acid inducible gene I and b-catenin. Growing evidence has indicated a dual role for HDAC6 in viral infection and pathogenesis: HDAC6 may represent a host defence mechanism against viral infection by modulating microtubule acetylation, triggering antiviral immune response and stimulating protective autophagy, or it may be hijacked by the virus to enhance proinflammatory response. In this review, we will highlight current data illustrating the complexity and importance of HDAC6 in viral pathogenesis. We will summarize the structure and functional specificity of HDAC6, and its deacetylaseand ubiquitin-dependent activity in key cellular events in response to virus infection. We will also discuss how HDAC6 exerts its direct or indirect histone modification ability in viral lytic-latency switch.

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The Ezrin-Radixin-Moesin Family Member Ezrin Regulates Stable Microtubule Formation and Retroviral Infection

Cited by 50 publications

References 39 publications

Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes

Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes

The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection

Cellular defence or viral assist: the dilemma of HDAC6

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