168 research outputs found

    Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

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    Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal. In cell lines and HIV-1 patient PBMCs, the Schlafen 12 protein (SLFN12) is shown to be an HIV-1 restriction factor that inhibits HIV-1 replication and virus reactivatio

    Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

    Get PDF
    Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.We thank Drs Yingying Li, Feng Gao and Beatrice H. Hahn for providing codon-optimized HIV-1 Gag expression vector, Drs James Hoxie and Susan Zolla-Pazner for supplying anti-Nef and -p24 antibodies, respectively through the NIH AIDS reagent program. We also thank Dr Song Gao for providing SLFN13-tRNA structure information, and Dr Maria-Eugenia Gas Lopez and Dr Ester Gea-Mallorquí for advise. This work was supported by following grants: M.K.I., JSPS Oversea Research Fellowship and Takeda Science Foundation; A.E.C., PT17/0009/0019 (ISCIII/MINECO and FEDER); M.J.B., RTI2018-101082-B-I00 and PID2021-123321OB-I00 [MINECO/FEDER]), and the Miguel Servet program by ISCIII (CP17/00179 and CPII22/00005); C.B., M.R.R., C.D.C., European Union’s Horizon 2020 research and innovation program under grant agreement 681137-EAVI2020 and NIH grant P01-AI131568; J.D., the Spanish Ministry of Science and Innovation (PID2019106959RB-I00/AEI/10.13039/501100011033); A.M., the Spanish Ministry of Science and Innovation (PID2019-106323RB-I00 AEI//10.13039/501100011033) and the institutional “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M).info:eu-repo/semantics/publishedVersio

    Spontaneous flow reversals in Rayleigh-Bénard convection of a liquid metal

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    We report a finding of spontaneous flow reversals of roll-like patterns in liquid gallium Rayleigh-Bénard convection. The vessel has a square geometry with an aspect ratio of 5, and a horizontal magnetic field is applied to align the rolls. The flow patterns were visualized by ultrasonic velocity measurements, and the processes of the reversal were clearly observed. The basic flow pattern observed in the vessel is a four-roll structure with its axis parallel to the magnetic field. Emergence of a new circulation at a corner of the vessel causes flow reversal with reorganization of the whole pattern. The flow keeps relatively steady four-roll structure for most of the duration, while the reversal of it is over in a short time. The reversals of the flow occur randomly with the interval time between reversals being much longer than the circulation time

    Convection patterns in a liquid metal under an imposed horizontal magnetic field

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    We performed laboratory experiments of Rayleigh-Bénard convection with liquid gallium under various intensities of a uniform imposed horizontal magnetic field. An ultrasonic velocity profiling method was used to visualize the spatiotemporal structure of the flows with simultaneous monitoring of the temperature fluctuations in the liquid gallium layer. The explored Rayleigh numbers Ra range from the critical value for onset of convection to 105; the Chandrasekhar number Q covers values up to 1100. A regime diagram of the convection patterns was established in relation to the Ra and Q values for a square vessel with aspect ratio 5. We identified five flow regimes: (I) a fluctuating large-scale pattern without rolls, (II) weakly constrained rolls with fluctuations, (III) a continuous oscillation of rolls, (IV) repeated roll number transitions with random reversals of the flow direction, and (V) steady two-dimensional (2D) rolls. These flow regimes are classified by the Ra/Q values, the ratio of the buoyancy to the Lorentz force. Power spectra from the temperature time series indicate that regimes I and II have the features of developed turbulence, while the other regimes do not. The region of steady 2D rolls (Busse balloon) extends to high Ra values in the present setting by a horizontal magnetic field and regime V is located inside the Busse balloon. Concerning the instabilities of the steady 2D rolls, regime III is the traveling wave convection developed from the oscillatory instability. Regime IV can be regarded as a state of phase turbulence, which is induced by intermittent occurrences of the skewed-varicose instability

    Detailed investigation of thermal convection in a liquid metal under a horizontal magnetic field: Suppression of oscillatory flow observed by velocity profiles

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    Thermal convection experiments in a liquid gallium layer were carried out with various intensities of uniform horizontal magnetic fields. The gallium layer was in a rectangular vessel with a 4:1:1 length ratio (1 is the height), where the magnetic field is applied in the direction normal to the longest vertical wall. An ultrasonic velocity profiling method was used to visualize the spatiotemporal variations in the flow pattern, and the temperature fluctuations in the gallium layer were also monitored. The observed flow pattern without a magnetic field shows oscillating rolls with axes normal to the longest vertical wall of the vessel. The oscillatory motion of the flow pattern was suppressed when increasing the applied magnetic field. The flow behavior was characterized by the fluctuation amplitude of the oscillation and the frequency in the range of Rayleigh numbers from 9.3 x 10^[3] to 3.5 x 10^[5] and Chandrasekhar numbers 0-1900. The effect of the horizontal magnetic field on the flow pattern may be summarized into three regimes with increases in the magnetic intensity: (1) no effect of the magnetic field, (2) a decrease in the oscillation of the roll structure, and (3) a steady two-dimensional roll structure with no oscillation. These regimes may be explained as a result of an increase in the dominance of Lorentz forces over inertial forces. The power spectrum from the temperature time series showed the presence of a convective-inertial subrange above Rayleigh numbers of 7 x 10^[4], which suggests that turbulence has developed, and such a subrange was commonly observed above this Rayleigh number even with applied magnetic fields when the rolls oscillate
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