Publications

2017
Casadevall, Arturo, and Thomas Shenk. “The mBio American Academy of Microbiology Submission Track in 2017.”. MBio 81 (2017). Web.
Levin, Jeremy M, et al.US immigration order strikes against biotech.”. Nat Biotechnol 35.3 (2017): , 35, 3, 204-206. Web.
2016
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. Infect Immun 84.9 (2016): , 84, 9, 2407-8. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. Antimicrob Agents Chemother 60.9 (2016): , 60, 9, 5109-10. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. Clin Microbiol Rev 29.4 (2016): , 29, 4, i-ii. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. mSystems 14 (2016). Web.Abstract
Many scientists attempt to publish their work in a journal with the highest possible journal impact factor (IF). Despite widespread condemnation of the use of journal IFs to assess the significance of published work, these numbers continue to be widely misused in publication, hiring, funding, and promotion decisions (1, 2).
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. J Clin Microbiol 54.9 (2016): , 54, 9, 2216-7. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. Appl Environ Microbiol 82.18 (2016): , 82, 18, 5479-80. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. Microbiol Mol Biol Rev 80.3 (2016): , 80, 3, i-ii. Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. MBio 74 (2016). Web.
Casadevall, Arturo, et al.ASM Journals Eliminate Impact Factor Information from Journal Websites.”. mSphere 14 (2016). Web.Abstract
Many scientists attempt to publish their work in a journal with the highest possible journal impact factor (IF). Despite widespread condemnation of the use of journal IFs to assess the significance of published work, these numbers continue to be widely misused in publication, hiring, funding, and promotion decisions (1, 2).
Imperiale, Michael J, Thomas Shenk, and Stefano Bertuzzi. “mSphereDirect: Author-Initiated Peer Review of Manuscripts.”. mSphere 16 (2016). Web.
2015
Casadevall, Arturo, et al.Dual-Use Research of Concern (DURC) Review at American Society for Microbiology Journals.”. MBio 64 (2015): , 6, 4, e01236. Web.
Purdy, John G, Thomas Shenk, and Joshua D Rabinowitz. “Fatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication.”. Cell Rep 10.8 (2015): , 10, 8, 1375-85. Web.Abstract
Human cytomegalovirus (HCMV) infection rewires host-cell metabolism, upregulating flux from glucose into acetyl-CoA to feed fatty acid metabolism, with saturated very-long-chain fatty acids (VLFCAs) required for production of infectious virion progeny. The human genome encodes seven elongase enzymes (ELOVL) that extend long-chain fatty acids into VLCFA. Here, we identify ELOVL7 as pivotal for HCMV infection. HCMV induces ELOVL7 by more than 150-fold. This induction is dependent on mTOR and SREBP-1. ELOVL7 knockdown or mTOR inhibition impairs HCMV-induced fatty acid elongation, HCMV particle release, and infectivity per particle. ELOVL7 overexpression enhances HCMV replication. During HCMV infection, mTOR activity is maintained by the viral protein pUL38. Expression of pUL38 is sufficient to induce ELOVL7, and pUL38-deficient virus is partially defective in ELOVL7 induction and fatty acid elongation. Thus, through its ability to modulate mTOR and SREBP-1, HCMV induces ELOVL7 to synthesize the saturated VLCFA required for efficient virus replication.
Oberstein, Adam, et al.Human cytomegalovirus pUL97 kinase induces global changes in the infected cell phosphoproteome.”. Proteomics 15.12 (2015): , 15, 12, 2006-22. Web.Abstract
Replication of human cytomegalovirus (HCMV) is regulated in part by cellular kinases and the single viral Ser/Thr kinase, pUL97. The virus-coded kinase augments the replication of HCMV by enabling nuclear egress and altering cell cycle progression. These roles are accomplished through direct phosphorylation of nuclear lamins and the retinoblastoma protein, respectively. In an effort to identify additional pUL97 substrates, we analyzed the phosphoproteome of SILAC-labeled human fibroblasts during infection with either wild-type HCMV or a pUL97 kinase-dead mutant virus. Phosphopeptides were enriched over a titanium dioxide matrix and analyzed by high-resolution MS. We identified 157 unambiguous phosphosites from 106 cellular and 17 viral proteins whose phosphorylation required UL97. Analysis of peptides containing these sites allowed the identification of several candidate pUL97 phosphorylation motifs, including a completely novel phosphorylation motif, LxSP. Substrates harboring the LxSP motif were enriched in nucleocytoplasmic transport functions, including a number of components of the nuclear pore complex. These results extend the known functions of pUL97 and suggest that modulation of nuclear pore function may be important during HCMV replication.
Ziehr, Benjamin, et al.Human cytomegalovirus TRS1 protein associates with the 7-methylguanosine mRNA cap and facilitates translation.”. Proteomics 15.12 (2015): , 15, 12, 1983-94. Web.Abstract
Viruses rely on the host translation machinery for the synthesis of viral proteins. Human cells have evolved sensors that recognize viral RNAs and inhibit mRNA translation in order to limit virus replication. Understanding how viruses manipulate the host translation machinery to gain access to ribosomes and disable the antiviral response is therefore a critical aspect of the host/pathogen interface. In this study, we used a proteomics approach to identify human cytomegalovirus (HCMV) proteins that might contribute to viral mRNA translation. The HCMV TRS1 protein (pTRS1) associated with the 7-methylguanosine mRNA cap, increased the total level of protein synthesis, and colocalized with mRNAs undergoing translation initiation during infection. pTRS1 stimulated translation of a nonviral reporter gene and increased the translation of a reporter containing an HCMV 5' untranslated region (5'UTR) to a greater extent. The preferential effect of pTRS1 on translation of an mRNA containing a viral 5'UTR required the pTRS1 RNA and double-stranded RNA-dependent protein kinase (PKR)-binding domains, and was likely the result of PKR inhibition. However, pTRS1 also stimulated the total level of protein synthesis and translation directed by an HCMV 5'UTR in cells lacking PKR. Thus our results demonstrate that pTRS1 stimulates translation through both PKR-dependent and PKR-independent mechanisms.
Casadevall, Arturo, and Thomas Shenk. “The Justification for the Academy Track in mBio.”. MBio 64 (2015). Web.
2014
Dermody, Terence S, et al.The decision to publish an avian H7N1 influenza virus gain-of-function experiment.”. MBio 55 (2014): , 5, 5, e01985-14. Web.
Shenk, Thomas, and James C Alwine. “Human Cytomegalovirus: Coordinating Cellular Stress, Signaling, and Metabolic Pathways.”. Annu Rev Virol 11 (2014): , 1, 1, 355-74. Web.Abstract
Viruses face a multitude of challenges when they infect a host cell. Cells have evolved innate defenses to protect against pathogens, and an infecting virus may induce a stress response that antagonizes viral replication. Further, the metabolic, oxidative, and cell cycle state may not be conducive to the viral infection. But viruses are fabulous manipulators, inducing host cells to use their own characteristic mechanisms and pathways to provide what the virus needs. This article centers on the manipulation of host cell metabolism by human cytomegalovirus (HCMV). We review the features of the metabolic program instituted by the virus, discuss the mechanisms underlying these dramatic metabolic changes, and consider how the altered program creates a synthetic milieu that favors efficient HCMV replication and spread.
Sharon-Friling, Ronit, and Thomas Shenk. “Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles.”. Proc Natl Acad Sci U S A 111.12 (2014): , 111, 12, E1140-8. Web.Abstract
The human cytomegalovirus immediate-early protein pUL37x1 induces the release of Ca(2+) stores from the endoplasmic reticulum into the cytosol. This release causes reorganization of the cellular actin cytoskeleton with concomitant cell rounding. Here we demonstrate that pUL37x1 activates Ca(2+)-dependent protein kinase Cα (PKCα). Both PKCα and Rho-associated protein kinases are required for actin reorganization and cell rounding; however, only PKCα is required for the efficient production of virus progeny, arguing that HCMV depends on the kinase for a second function. PKCα activation is also needed for the production of large (1-5 μm) cytoplasmic vesicles late after infection. The production of these vesicles is blocked by inhibition of fatty acid or phosphatidylinositol-3-phosphate biosynthesis, and the failure to produce vesicles is correlated with substantially reduced production of enveloped virus capsids. These results connect earlier work identifying a requirement for lipid synthesis with specific morphological changes, and support the argument that the PKCα-induced large vesicles are either required for the efficient production of mature virus particles or serve as a marker for the process.

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