A novel host factor for human respiratory syncytial virus

Mehedi, Masfique; Collins, Peter L.; Buchholz, Ursula J.

doi:10.1080/19420889.2017.1319025

Cited by 15 publications

(17 citation statements)

References 16 publications

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“…Together, these observations suggest that long filopodia specifically contribute to cell-cell HIV spread, whereas lamellipodia are less important for this process. This is consistent with findings from other enveloped viruses where filopodia have been associated with the ability to mediate cell-cell viral transfer [103][104][105][106][107]. Indeed, we have previously observed HIV-Filopodia to mediate hundreds of contacts per hour between relevant primary HIV target cells, with filopodial activity often preceding VS formation [18].…”

Section: Discussionsupporting

confidence: 91%

HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread

Aggarwal

Stella

Henry

et al. 2019

Preprint

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F-Actin remodelling is important for the spread of HIV via cell-cell contacts, yet the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell-cell contact, providing Cdc42 and IQGAP1 were present. From these observations we conclude that out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, maturation of cell-cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.

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Section: Discussionsupporting

confidence: 91%

HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread

Aggarwal

Stella

Henry

et al. 2019

Preprint

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“…Notably, we also observed non-classical RNA-binding proteins such as ANXA1 or ACTR2 among highly-connected proteins in this network. ACTR2 has been identified as a host factor for respiratory syncytial virus (RSV) infection and is involved in cytoskeleton reorganization and filipodia formation, which is thought to promote virus spreading 74,75 . This observation is consistent with recent work that demonstrated that SARS-CoV-2 infection induced a dramatic increase in filopodia, and viral particles localized to and emerged from these protrusions 9 .…”

Section: Connectivity Map Of Sars-cov-2 Rna Binders and Regulated Hosmentioning

confidence: 99%

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

Schmidt

Lareau

Keshishian

et al. 2020

Preprint

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SARS-CoV-2 infections pose a global threat to human health and an unprecedented research challenge. Among the most urgent tasks is obtaining a detailed understanding of the molecular interactions that facilitate viral replication or contribute to host defense mechanisms in infected cells. While SARS-CoV-2 co-opts cellular factors for viral translation and genome replication, a comprehensive map of the host cell proteome in direct contact with viral RNA has not been elucidated. Here, we use RNA antisense purification and mass spectrometry (RAP-MS) to obtain an unbiased and quantitative picture of the human proteome that directly binds the SARS-CoV-2 RNA in infected human cells. We discover known host factors required for coronavirus replication, regulators of RNA metabolism and host defense pathways, along with dozens of potential drug targets among direct SARS-CoV-2 binders. We further integrate the SARS-CoV-2 RNA interactome with proteome dynamics induced by viral infection, linking interactome proteins to the emerging biology of SARS-CoV-2 infections. Validating RAP-MS, we show that CNBP, a regulator of proinflammatory cytokines, directly engages the SARS-CoV-2 RNA. Supporting the functional relevance of identified interactors, we show that the interferon-induced protein RYDEN suppresses SARS-CoV-2 ribosomal frameshifting and demonstrate that inhibition of SARS-CoV-2-bound proteins is sufficient to manipulate viral replication. The SARS-CoV-2 RNA interactome provides an unprecedented molecular perspective on SARS-CoV-2 infections and enables the systematic dissection of host dependency factors and host defense strategies, a crucial prerequisite for designing novel therapeutic strategies.

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“…Actin-related protein 2, identified as a proviral host factor involved in virus egress and dissemination in a similar screen using the tissue-culture adapted HRSV A2 strain (12, 39), did not reach significance in our screen. However, cofilin 1, which associates with the viral matrix (M) protein in HRSV particles and may modulate particle assembly and release (40, 41), was among the top hits.…”

Section: Resultsmentioning

confidence: 63%

Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae

Anderson

Pfeffermann

Kim

et al. 2019

mBio

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Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation. IMPORTANCE The Paramyxoviridae and Pneumoviridae families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.

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A novel host factor for human respiratory syncytial virus

Cited by 15 publications

References 16 publications

HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread

HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae

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