Novel insights into human respiratory syncytial virus-host factor interactions through integrated proteomics and transcriptomics analysis

Dapat, Clyde; Oshitani, Hitoshi

doi:10.1586/14787210.2016.1141676

Cited by 25 publications

(17 citation statements)

References 73 publications

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“…Two host-directed antiviral drugs are maraviroc, a CCR5 receptor antagonist approved for HIV therapy, and alisporivir, a cyclophylin inhibitor that is undergoing Phase III tests for hepatitis C treatment [5]. Specific host proteins were proven to be critical for the replication of diverse unrelated viruses [6], yet the array of possible cellular targets (the 'virus-host interactome') is continuously growing, as recently reviewed for influenza [7] and RSV [8].…”

Section: Introductionmentioning

confidence: 99%

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Tonelli

Naesens

Gazzarrini

et al. 2017

European Journal of Medicinal Chemistry

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We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. Most analogues proved active against influenza B virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC = 0.060 μM), and markedly exceeded (up to 327 times) the antiviral efficacy of ribavirin. Activity was also observed for two influenza A strains, including a virus with the S31N mutant form of M2 proton channel, which is the most prevalent resistance mutation for amantadine. Importantly, the compounds displayed nanomolar activity against RSV and a superior selectivity index, since the ratio of cytotoxic to antiviral concentration was >10,000 for the three most active compounds 11, 14 and 16 (EC ∼0.008 μM), far surpassing the potency and safety profile of the licensed drug ribavirin (EC = 5.8 μM, SI > 43).

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Section: Introductionmentioning

confidence: 99%

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Tonelli

Naesens

Gazzarrini

et al. 2017

European Journal of Medicinal Chemistry

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“…We identi ed 9 out of 15 genes from the fatty acid pathway were down modulated compared to HC (Figure 5d). Many of these pathways enriched have been found to be modulated upon RSV infection in human and animal models, including in cotton rat lung tissue 25,26 .…”

Section: Resultsmentioning

confidence: 99%

Metatranscriptomics to characterize respiratory virome, microbiome, and host response directly from clinical samples

Rajagopala

Bakhoum

Pakala

et al. 2020

Preprint

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We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low-biomass clinical samples. Using nasal swab samples, we have demonstrated that this method captures the comprehensive RNA virome with sufficient sequencing depth required to assemble complete genomes. We find a surprisingly high-frequency of Respiratory Syncytial Virus (RSV) and Coronavirus (CoV) in healthy children, and a high frequency of RSV-A and RSV-B co-infections in children with symptomatic RSV. In addition, we have characterized commensal and pathogenic bacteria, and fungi at the species-level. Functional analysis of bacterial transcripts revealed H. influenzae was highly active in symptomatic RSV subjects. Host transcriptome shows upregulation of the innate immune system, antiviral response and inflammasome pathway, and down regulation of fatty-acids pathway. This method is broadly applicable to infer transcriptome landscape of an infected system, surveil respiratory infections, and to sequence RNA viruses directly from clinical samples.

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“…Different reports reveal a relationship between RSV and the host cell SUMOylation machinery. Thus, an association between a cluster of host proteins involved in the SUMOylation process and the phosphoprotein (P) of the virus has been found after integration of proteome and transcriptome datasets [61]. In addition, SUMO seems to play a role in the pathogenesis of the virus [62].…”

Section: Pneumoviridaementioning

confidence: 99%

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Motiam

Vidal

Seoane

et al. 2020

Advances in Experimental Medicine and Biology

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SUMO is a ubiquitin-like protein that covalently binds to lysine residues of target proteins and regulates many biological processes such as protein subcellular localization or stability, transcription, DNA repair, innate immunity, or antiviral defense. SUMO has a critical role in the signaling pathway governing type I interferon (IFN) production, and among the SUMOylation substrates are many IFN-induced proteins. The overall effect of IFN is increasing global SUMOylation, pointing to SUMO as part of the antiviral stress response. Viral agents have developed different mechanisms to counteract the antiviral activities exerted by SUMO, and some viruses have evolved to exploit the host SUMOylation machinery to modify their own proteins. The exploitation of SUMO has been mainly linked to nuclear replicating viruses due to the predominant nuclear localization of SUMO proteins and enzymes involved in SUMOylation. However, SUMOylation of numerous viral proteins encoded by RNA viruses replicating at the cytoplasm has been lately described. Whether nuclear localization of these viral proteins is required for their SUMOylation is unclear. Here, we summarize the studies on exploitation of SUMOylation by cytoplasmic RNA viruses and discuss about the requirement for nuclear localization of their proteins. Keywords SUMO · RNA viruses · Interferon SUMO ConjugationSUMOylation consists in the covalent attachment of the small ubiquitin-like modifier (SUMO) proteins to specific lysine residues of a target protein. This conjugation is an enzymatic process that occurs in cascade. The precursor SUMO proteins are proteolytically processed to the

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Novel insights into human respiratory syncytial virus-host factor interactions through integrated proteomics and transcriptomics analysis

Cited by 25 publications

References 73 publications

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Metatranscriptomics to characterize respiratory virome, microbiome, and host response directly from clinical samples

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

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