Binding and Relocalization of PKR 1 by Murine Cytomegalovirus

Many viruses have evolved mechanisms to evade the repression of translation mediated by protein kinase R (PKR). In the case of murine cytomegalovirus (MCMV), the protein products of two essential genes, m142 and m143, bind to dsRNA and block phosphorylation of PKR and eukaryotic initiation factor 2. A distinctive feature of MCMV is that two proteins are required to block PKR activation whereas other viral dsRNA-binding proteins that prevent PKR activation contain all the necessary functions in a single protein. In order to better understand the mechanism by which MCMV evades the PKR response, we investigated the associations of pm142 and pm143 with each other and with PKR. Both pm142 and pm143 interact with PKR in infected and transfected cells. However, the ~200 kDa pm142:pm143 complex that forms in these cells does not contain substantial amounts of PKR, suggesting that the interactions between pm142:pm143 and PKR are unstable or transient. The stable, soluble pm142:pm143 complex appears to be a heterotetramer consisting of two molecules of pm142 associated with each other and each one binding to and stabilizing a monomer of pm143. MCMV infection also causes relocalization of PKR into the nucleus and to an insoluble cytoplasmic compartment. These results suggest a model in which the pm142:pm143 multimer interacts with PKR and causes its sequestration in cellular compartments where it is unable to shut off translation and repress viral replication

Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals.

IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires

Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts

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Atmospheric circulation of hot Jupiters: Coupled radiative-dynamical general circulation model simulations of HD 189733b and HD 209458b

We present global, three-dimensional numerical simulations of HD 189733b and HD 209458b that couple the atmospheric dynamics to a realistic representation of non-gray cloud-free radiative transfer. The model, which we call the Substellar and Planetary Atmospheric Radiation and Circulation (SPARC) model, adopts the MITgcm for the dynamics and uses the radiative model of McKay, Marley, Fortney, and collaborators for the radiation. Like earlier work with simplified forcing, our simulations develop a broad eastward equatorial jet, mean westward flow at higher latitudes, and substantial flow over the poles at low pressure. For HD 189733b, our simulations without TiO and VO opacity can explain the broad features of the observed 8 and 24-micron light curves, including the modest day-night flux variation and the fact that the planet/star flux ratio peaks before the secondary eclipse. Our simulations also provide reasonable matches to the Spitzer secondary-eclipse depths at 4.5, 5.8, 8, 16, and 24 microns and the groundbased upper limit at 2.2 microns. However, we substantially underpredict the 3.6-micron secondary-eclipse depth, suggesting that our simulations are too cold in the 0.1-1 bar region. Predicted temporal variability in secondary-eclipse depths is ~1% at Spitzer bandpasses, consistent with recent observational upper limits at 8 microns. We also show that nonsynchronous rotation can significantly alter the jet structure. For HD 209458b, we include TiO and VO opacity; these simulations develop a hot (>2000 K) dayside stratosphere. Despite this stratosphere, we do not reproduce current Spitzer photometry of this planet. Light curves in Spitzer bandpasses show modest phase variation and satisfy the observational upper limit on day-night phase variation at 8 microns. (abridged)Comment: 20 pages (emulate-apj format), 21 figures, final version now published in ApJ. Includes expanded discussion of radiative-transfer methods and two new figure

A Disk Around the Planetary-Mass Companion GSC 06214-00210 b: Clues About the Formation of Gas Giants on Wide Orbits

We present Keck/OSIRIS 1.1-1.8 um adaptive optics integral field spectroscopy of the planetary-mass companion to GSC 06214-00210, a member of the ~5 Myr Upper Scorpius OB association. We infer a spectral type of L0+/-1, and our spectrum exhibits multiple signs of youth. The most notable feature is exceptionally strong PaBeta emission (EW=-11.4 +/- 0.3 A) which signals the presence of a circumplanetary accretion disk. The luminosity of GSC 06214-00210 b combined with its age yields a model-dependent mass of 14 +/- 2 MJup, making it the lowest-mass companion to show evidence of a disk. With a projected separation of 320 AU, the formation of GSC 06214-00210 b and other very low-mass companions on similarly wide orbits is unclear. One proposed mechanism is formation at close separations followed by planet-planet scattering to much larger orbits. Since that scenario involves a close encounter with another massive body, which is probably destructive to circumplanetary disks, it is unlikely that GSC 06214-00210 b underwent a scattering event in the past. This implies that planet-planet scattering is not solely responsible for the population of gas giants on wide orbits. More generally, the identification of disks around young planetary companions on wide orbits offers a novel method to constrain the formation pathway of these objects, which is otherwise notoriously difficult to do for individual systems. We also refine the spectral type of the primary from M1 to K7 and detect a mild (2-sigma) excess at 22 um using WISE photometry.Comment: 25 pages, 13 figures; Accepted by Ap

First Light LBT AO Images of HR 8799 bcde at 1.65 and 3.3 Microns: New Discrepancies between Young Planets and Old Brown Dwarfs

As the only directly imaged multiple planet system, HR 8799 provides a unique opportunity to study the physical properties of several planets in parallel. In this paper, we image all four of the HR 8799 planets at H-band and 3.3 microns with the new LBT adaptive optics system, PISCES, and LBTI/LMIRCam. Our images offer an unprecedented view of the system, allowing us to obtain H and 3.3$ micron photometry of the innermost planet (for the first time) and put strong upper-limits on the presence of a hypothetical fifth companion. We find that all four planets are unexpectedly bright at 3.3 microns compared to the equilibrium chemistry models used for field brown dwarfs, which predict that planets should be faint at 3.3 microns due to CH4 opacity. We attempt to model the planets with thick-cloudy, non-equilibrium chemistry atmospheres, but find that removing CH4 to fit the 3.3 micron photometry increases the predicted L' (3.8 microns) flux enough that it is inconsistent with observations. In an effort to fit the SED of the HR 8799 planets, we construct mixtures of cloudy atmospheres, which are intended to represent planets covered by clouds of varying opacity. In this scenario, regions with low opacity look hot and bright, while regions with high opacity look faint, similar to the patchy cloud structures on Jupiter and L/T transition brown-dwarfs. Our mixed cloud models reproduce all of the available data, but self-consistent models are still necessary to demonstrate their viability.Comment: Accepted to Ap

Large Scale Searches for Brown Dwarfs and Free-Floating Planets

Searches of large scale surveys have resulted in the discovery of over 1000 brown dwarfs in the Solar neighbourhood. In this chapter we review the progress in finding brown dwarfs in large datasets, highlighting the key science goals, and summarising the surveys that have contributed most significantly to the current sample.Comment: Accepted to appear in the Handbook of Exoplanets (Springer); Editors: Hans J. Deeg & Juan Antonio Belmont

Double-Stranded RNA Binding by Human Cytomegalovirus pTRS1

The human cytomegalovirus (HCMV) TRS1 and IRS1 genes rescue replication of vaccinia virus (VV) that has a deletion of the double-stranded RNA binding protein gene E3L (VVΔE3L). Like E3L, these HCMV genes block the activation of key interferon-induced, double-stranded RNA (dsRNA)-activated antiviral pathways. We investigated the hypothesis that the products of these HCMV genes act by binding to dsRNA. pTRS1 expressed by cell-free translation or by infection of mammalian cells with HCMV or recombinant VV bound to dsRNA. Competition experiments revealed that pTRS1 preferentially bound to dsRNA compared to double-stranded DNA or single-stranded RNA. 5′- and 3′-end deletion analyses mapped the TRS1 dsRNA-binding domain to amino acids 74 through 248, a region of identity to pIRS1 that contains no homology to known dsRNA-binding proteins. Deletion of the majority of this region (Δ86-246) completely abrogated dsRNA binding. To determine the role of the dsRNA-binding domain in the rescue of VVΔE3L replication, wild-type or deletion mutants of TRS1 were transfected into HeLa cells, which were then infected with VVΔE3L. While full-length TRS1 rescued VVΔE3L replication, deletion mutants affecting a carboxy-terminal region of TRS1 that is not required for dsRNA binding failed to rescue VVΔE3L. Analyses of stable cell lines revealed that the carboxy-terminal domain is necessary to prevent the shutoff of protein synthesis and the phosphorylation of eIF2α after VVΔE3L infection. Thus, pTRS1 contains an unconventional dsRNA-binding domain at its amino terminus, but a second function involving the carboxy terminus is also required for countering host cell antiviral responses