Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4+ target cells

Yavlovich, Amichai; Viard, Mathias; Zhou, Ming; Veenstra, Timothy D.; Wang, Ji Ming; Gong, Wanghua; Heldman, Eliahu; Blumenthal, Robert; Raviv, Yossef

doi:10.1182/blood-2011-12-399063

Cited by 24 publications

(16 citation statements)

References 36 publications

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“…6C and D). The ATPase activity of ATP5B was recently shown to be an important factor in influenza A virus release and human immunodeficiency virus 1 (HIV-1) cell-to-cell transfer (70,71). Our findings are consistent with a role for ATP5B in the energetics of virus release and suggest that this protein might be important for the release of a diverse range of viruses.…”

Section: Discussionsupporting

confidence: 85%

A Proteomics Survey of Junín Virus Interactions with Human Proteins Reveals Host Factors Required for Arenavirus Replication

Ziegler

Eisenhauer

Kelly

et al. 2018

J Virol

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Arenaviruses are negative-strand, enveloped RNA viruses that cause significant human disease. In particular, Junín mammarenvirus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. At present, little is known about the cellular proteins that the arenavirus matrix protein (Z) hijacks to accomplish its various functions, including driving the process of virus release. Further, there is a little knowledge regarding host proteins incorporated into arenavirus particles and their importance for virion function. To address these deficiencies, we used mass spectrometry to identify human proteins that (i) interact with the JUNV matrix protein inside of cells or within virus-like particles (VLPs) and/or (ii) are incorporated into JUNV strain Candid #1 particles. Bioinformatic analyses revealed that multiple classes of human proteins were overrepresented in the datasets, including ribosomal proteins, Ras superfamily proteins, and endosomal sorting complex required for transport (ESCRT) proteins. Several of these proteins were required for the propagation of JUNV (ARF1, ATP6V0D1 and PRDX3), lymphocytic choriomeningitis mammarenavirus (LCMV) (Rab5c), or both viruses (ATP5B, IMPDH2). Further, we show that release of infectious JUNV particles, but not LCMV particles, requires a functional ESCRT pathway and that ATP5B and IMPDH2 are required for JUNV budding. In summary, we have provided a large-scale map of host machinery that associates with JUNV and identified key human proteins required for its propagation. This dataset provides a resource for the field to guide antiviral target discovery and to better understand the biology of the arenavirus matrix protein and the importance of host proteins for virion function. Arenaviruses are deadly human pathogens for which there are no United States Food and Drug Administration-approved vaccines and only limited treatment options. Little is known about the host proteins that are incorporated into arenavirus particles or that associate with its multifunctional matrix protein. Using Junín mammarenavirus (JUNV), the causative agent of Argentine hemorrhagic fever, as a model organism, we mapped the human proteins that are incorporated into JUNV particles or that associate with the JUNV matrix protein. Functional analysis revealed host machinery that is required for JUNV propagation, including the cellular ESCRT pathway. This study improves our understanding of critical arenavirus-host interactions and provides a dataset that will guide future studies to better understand arenavirus pathogenesis and identify novel host proteins that can be therapeutically targeted.

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Section: Discussionsupporting

confidence: 85%

A Proteomics Survey of Junín Virus Interactions with Human Proteins Reveals Host Factors Required for Arenavirus Replication

Ziegler

Eisenhauer

Kelly

et al. 2018

J Virol

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“…Just as ectopic ATP synthase has the ability to bind to many different ligands (apolipoprotein A-I, angiostatin, β amyloid oligomers, etc.) (22 , 23 , 31 , 32) and to transfer HIV-1 from antigen-presenting cells to CD4 + cells (33) , the sarcolemmal OXPHOS complexes may have as yet unknown non-canonical functions. Thus, a direction for future research on the sarcolemmal OXPHOS proteins is to identify their novel non-canonical functions.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial oxidative phosphorylation complexes exist in the sarcolemma of skeletal muscle

et al. 2016

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Although proteomic analyses have revealed the presence of mitochondrial oxidative phosphorylation (OXPHOS) proteins in the plasma membrane, there have been no in-depth evaluations of the presence or function of OXPHOS I-V in the plasma membrane. Here, we demonstrate the in situ localization of OXPHOS I-V complexes to the sarcolemma of skeletal muscle by immunofluorescence and immunohistochemistry. A portion of the OXPHOS I-V complex proteins was not co-stained with MitoTracker but co-localized with caveolin-3 in the sarcolemma of mouse gastrocnemius. Mitochondrial matrix-facing OXPHOS complex subunits were ectopically expressed in the sarcolemma of the non-permeabilized muscle fibers and C2C12 myotubes. The sarcolemmal localization of cytochrome c was also observed from mouse gastrocnemius muscles and C2C12 myotubes, as determined by confocal and total internal resonance fluorescence (TIRF) microscopy. Based on these data, we conclude that a portion of OXPHOS complexes is localized in the sarcolemma of skeletal muscle and may have non-canonical functions. [BMB Reports 2016; 49(2): 116-121]

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“…Another drug, Bz-423 that induces apoptosis in lymphoid cells, has been found to inhibit the mitochondrial ATP synthase [ 13 ]. Also, it is been shown that ectopic ATP synthase may be a suitable molecular target for inhibiting HIV-1 proliferation in vivo [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

2015

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We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase.

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Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4+ target cells

Cited by 24 publications

References 36 publications

A Proteomics Survey of Junín Virus Interactions with Human Proteins Reveals Host Factors Required for Arenavirus Replication

A Proteomics Survey of Junín Virus Interactions with Human Proteins Reveals Host Factors Required for Arenavirus Replication

Mitochondrial oxidative phosphorylation complexes exist in the sarcolemma of skeletal muscle

Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

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