Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Inclusive J/ψ production at mid-rapidity in pp collisions at √s = 5.02 TeV

Inclusive J/ψ production is studied in minimum-bias proton-proton collisions at a centre-of-mass energy of s = 5.02 TeV by ALICE at the CERN LHC. The measurement is performed at mid-rapidity (|y| < 0.9) in the dielectron decay channel down to zero transverse momentum pT, using a data sample corresponding to an integrated luminosity of Lint = 19.4 ± 0.4 nb−1. The measured pT-integrated inclusive J/ψ production cross sec- tion is dσ/dy = 5.64 ± 0.22(stat.) ± 0.33(syst.) ± 0.12(lumi.) μb. The pT-differential cross section d2σ/dpTdy is measured in the pT range 0–10 GeV/c and compared with state-of- the-art QCD calculations. The J/ψ 〈pT〉 and 〈pT2〉 are extracted and compared with results obtained at other collision energies. [Figure not available: see fulltext.]

Measurement of Λ (1520) production in pp collisions at √s=7TeV and p–Pb collisions at √sNN=5.02TeV

The production of the Λ (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in p–Pb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ (1520) → pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p–Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, KS0, p, Λ) describes the shape of the Λ (1520) transverse momentum distribution up to 3.5GeV/c in p–Pb collisions. In the framework of this model, this observation suggests that the Λ (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ (1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p–Pb collisions on the Λ (1520) yield

Measurement of electrons from heavy-flavour hadron decays as a function of multiplicity in p-Pb collisions at √sNN = 5.02 TeV

The multiplicity dependence of electron production from heavy-flavour hadron decays as a function of transverse momentum was measured in p-Pb collisions at sNN = 5.02 TeV using the ALICE detector at the LHC. The measurement was performed in the centre-of-mass rapidity interval −1.07 < ycms< 0.14 and transverse momentum interval 2 < pT< 16 GeV/c. The multiplicity dependence of the production of electrons from heavy-flavour hadron decays was studied by comparing the pT spectra measured for different multiplicity classes with those measured in pp collisions (QpPb) and in peripheral p-Pb collisions (Qcp). The QpPb results obtained are consistent with unity within uncertainties in the measured pT interval and event classes. This indicates that heavy-flavour decay electron production is consistent with binary scaling and independent of the geometry of the collision system. Additionally, the results suggest that cold nuclear matter effects are negligible within uncertainties, in the production of heavy-flavour decay electrons at midrapidity in p-Pb collisions. [Figure not available: see fulltext.

Measurement of prompt D0, D+, D*+, and DS+ production in p–Pb collisions at √sNN = 5.02 TeV

The measurement of the production of prompt D0, D+, D*+, and DS+ mesons in proton–lead (p–Pb) collisions at the centre-of-mass energy per nucleon pair of sNN = 5.02 TeV, with an integrated luminosity of 292 ± 11 μb−1, are reported. Differential production cross sections are measured at mid-rapidity (−0.96 < ycms< 0.04) as a function of transverse momentum (pT) in the intervals 0 < pT< 36 GeV/c for D0, 1 < pT< 36 GeV/c for D+ and D*+, and 2 < pT< 24 GeV/c for D+ mesons. For each species, the nuclear modification factor RpPb is calculated as a function of pT using a proton-proton (pp) ref- erence measured at the same collision energy. The results are compatible with unity in the whole pT range. The average of the non-strange D mesons RpPb is compared with theoretical model predictions that include initial-state effects and parton transport model predictions. The pT dependence of the D0, D+, and D*+ nuclear modification factors is also reported in the interval 1 < pT< 36 GeV/c as a function of the collision centrality, and the central-to-peripheral ratios are computed from the D-meson yields measured in different centrality classes. The results are further compared with charged-particle measurements and a similar trend is observed in all the centrality classes. The ratios of the pT-differential cross sections of D0, D+, D*+, and DS+ mesons are also reported. The DS+ and D+ yields are compared as a function of the charged-particle multiplicity for several pT intervals. No modification in the relative abundances of the four species is observed with respect to pp collisions within the statistical and systematic uncertainties. [Figure not available: see fulltext.]

Measurement of charged jet cross section in pp collisions at s =5.02 TeV

The cross section of jets reconstructed from charged particles is measured in the transverse momentum range of

Measurement of ϒ(1S) Elliptic Flow at Forward Rapidity in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The first measurement of the ϒ(1S) elliptic flow coefficient (v_{2}) is performed at forward rapidity (2.