Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

Brügger, Britta; Krautkrämer, Ellen; Tibroni, Nadine; Munte, Cláudia Elisabeth; Rauch, Susanne; Leibrecht, Iris; Glass, Bärbel; Breuer, Sebastian; Geyer, Matthias; Kräusslich, Hans‐Georg; Kalbitzer, Hans Robert; Wieland, Felix; Fackler, Oliver T.

doi:10.1186/1742-4690-4-70

Cited by 71 publications

(65 citation statements)

References 77 publications

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“…Lipid rafts are the preferential sites of HIV-1 assembly and budding, and cholesterol content of lipid rafts determines the cholesterol content of virions, which is critical for virion infectivity. Cholesterol depletion of HIV-infected cells reduces infectivity of released virions, which was shown to correlate with the amount of virion-associated cholesterol and the activity of Nef ( 6,13 ). In addition, depletion of cellular cholesterol, which reduces the abundance of rafts, also reduces HIV-1 particle production ( 6,10 ).…”

Section: Lipid Raft Cholesterol Content Analysismentioning

confidence: 98%

HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux

Cui

Grant

Mukhamedova

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words cholesterol metabolism • cholesterol traffi cking • ATP binding cassette transporter A1 • human immunodeficiency virus Impairment of cholesterol metabolism plays a key role in pathogenesis of many disorders, most importantly cardiovascular and neurodegenerative diseases. Many infectious agents, from prions to parasites, affect cholesterol metabolism of the host. Microorganisms modify host cholesterol metabolism for two main reasons: to satisfy their own requirements for cholesterol at different stages of their life cycle, and to weaken the immune response of the host. These modifi cations may cause "unintended" consequences, triggering development of diseases that are not directly related to infection. This situation is exemplifi ed by the increased risk of atherosclerosis coincident with HIV infection. Targeting cholesterol metabolism for antimicrobial intervention, while at the same time correcting metabolic consequences of the infection, is a tempting possibility limited by the lack of knowledge about mechanisms of interaction between microorganisms and pathways of cholesterol metabolism in host cells.

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Section: Lipid Raft Cholesterol Content Analysismentioning

confidence: 98%

HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux

Cui

Grant

Mukhamedova

et al. 2012

Journal of Lipid Research

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“…Furthermore, HIV-1 envelope-mediated membrane fusion occurs in cholesterol-rich lipid domains. In this context, the viral protein Nef can modulate the lipid composition of virion and host cell micro-domains ("lipid raft") to enhance virus infectivity and propagation, by specific enrichment of sphingomyelin and cholesterol specifically in these sites [101][102][103].…”

Section: Glucose Management a Key Factor For Bioenergetic Needs Is mentioning

confidence: 99%

Current topics in HIV-1 pathogenesis: The emergence of deregulated immuno-metabolism in HIV-infected subjects

Dagenais-Lussier

Aounallah

Routy

et al. 2015

Cytokine & Growth Factor Reviews

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Abstract. HIV-1 infection results in long-lasting activation of the immune system including elevated production of pro-inflammatory cytokine/chemokines, and bacterial product release from gut into blood and tissue compartments, which are not fully restored by antiretroviral therapies. HIV-1 has also developed numerous strategies via viral regulatory proteins to hijack cell molecular mechanisms to enhance its own replication and dissemination. Here, we reviewed the relationship between viral proteins, immune activation/inflammation, and deregulated metabolism occurring in HIV-1-infected patients that ultimately dampens the protective innate and adaptive arms of immunity.Defining precisely the molecular mechanisms related to deregulated immuno-metabolism during HIV-1 infection could ultimately help in the development of novel clinical approaches to restore proper immune functions in these patients.

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“…The role of membrane rafts in the assembly and budding of enveloped viruses has been investigated for influenza virus [59,63,[150][151][152][153][154][155][156][157][158][159][160], HIV-1 [63,[161][162][163][164][165][166][167][168][169][170][171][172][173], HTLV-1 [174], measles virus (Paramyxoviridae) [63,175,176], Sendai virus [Paramyxoviridae] [177,178], Newcastle disease virus (NDV; Paramyxoviridae) [179,180], RSV [147,148,[181][182][183][184], HSV [185,186], murine cytomegalovirus (MCMV; Herpesviridae) [187], Ebola virus [70,188], Marburg virus [70], and vesicular stomatitis virus (VSV; Rhabdoviridae) …”

Section: Role Of Membrane Rafts In Virus Genome Replication Assemblymentioning

confidence: 99%

“…The N-terminus of Nef determines the differential membrane avidities and selective incorporation into a specific membrane raft for surface membranes or for subcellular membranes [170]. Moreover, Nef modulates the lipid composition of virions and host cell membrane rafts through activation of lipid kinases such as PI3K [171].…”

Section: Role Of Membrane Rafts In Virus Genome Replication Assemblymentioning

confidence: 99%

“…The cytoplasmic tail, but not the transmembrane domain and the ectodomain of F protein, plays a critical role in its cellular localization and production of infectious progeny virus, dependently on interaction of F protein with membrane rafts [183]. Moreover, like a function of HIV-1 Nef [171], RSV infection induces production of phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-triphosphate (PIP3) in the lipid composition of membrane rafts within virus inclusion bodies through lipid kinases containing PI3K. This change plays a role in the assembly and budding of progeny virus [184].…”

Section: Role Of Membrane Rafts In Virus Genome Replication Assemblymentioning

confidence: 99%

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Role of Membrane Rafts in Viral Infection

Takahashi¹,

Suzuki²

2009

TODJ

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Membrane rafts are small (10-200 nm), heterogeneous, highly dynamic, sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Many studies have established that membrane rafts play an important role in the process of virus infection cycle and virus-associated diseases. It is well known that many viral components or virus receptors are concentrated in the lipid microdomains. Viruses are divided into four main classes, nonenveloped RNA virus, enveloped RNA virus, nonenveloped DNA virus, and enveloped DNA virus. General virus infection cycle is also classified into two sections, the early stage (entry) and the late stage (assembly and budding of virion). Caveola-dependent endocytosis has been investigated mostly by analysis of cell entry of the SV40 representative of polyomaviruses. Thus, the study of membrane rafts has been partially advanced by virological researches. Membrane rafts also act as a scaffold of many cellular signal transductions. Involvement of membrane rafts in many virus-associated diseases is often responsible for up-or down-regulation of cellular signal transductions. What is the role of membrane rafts in virus replications? Viruses do not necessarily require and probably utilize membrane rafts for more efficiency in virus entry, viral genome replication, high-infective virion production, and cellular signaling activation toward advantageous virus replication. In this review, we described the involvement of membrane rafts in the virus life cycle and virus-associated diseases.

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Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

Cited by 71 publications

References 77 publications

HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux

HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux

Current topics in HIV-1 pathogenesis: The emergence of deregulated immuno-metabolism in HIV-infected subjects

Role of Membrane Rafts in Viral Infection

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