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In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway1. However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.

Thirty-seven isotopically highly anomalous presolar grains and one presolar grain Al 2 O 3 MgAl 2 O 4 from a separate of the Tieschitz H3.6 ordinary chondrite were identiÐed out of 17,000 isotopically normal refractory oxide grains by an automatic 16O/18O low mass resolution ion-imaging mapping technique in the ion microprobe. Eight additional presolar grains were found by high mass resolution Al 2 O 3 ion probe measurements of all three stable O isotopes in individual grains, including several that would have been missed by the ion-imaging search. Forty-Ðve of the grains were analyzed for their 16O/17O and 16O/18O ratios. Twenty-four grains were also analyzed for Al-Mg and 17 of them have large excesses of 26Mg, attributable to the radioactive decay of 26Al. The highly anomalous isotopic composition of the grains is evidence for their presolar, stellar origin.The 46 oxide grains of this study together with 42 previously identiÐed presolar grains were divided into four groups. These groups most likely comprise grains from distinct types of stellar sources. Group 1 grains have 17O excesses and moderate 18O depletions, relative to solar, and many of them exhibit 26Mg excesses as well. Group 2 grains have 17O excesses, large 18O depletions, and high inferred 26Al/27Al ratios. Group 3 grains have solar or higher 16O/17O and 16O/18O ratios. Group 4 grains have 17O and 18O enrichments. One grain of this study, T54, has an 16O/17O ratio of 71, lower than any preAl 2 O 3 viously observed, and 16O/18O much greater than the solar value.The O-isotopic compositions of Group 1 and Group 3 grains are consistent with an origin in O-rich red giant stars, which have undergone the Ðrst dredge-up. The range of O-isotopic ratios of these groups requires multiple stellar sources of di †erent masses and initial isotopic compositions and is well explained by a combination of Galactic chemical evolution and Ðrst dredge-up models. The inferred 26Al/27Al ratios of many of these grains indicate that they formed in thermally pulsing asymptotic branch (TP-AGB) stars that had undergone the third dredge-up. Group 2 grains probably formed in low-mass AGB stars as well, and their substantial 18O depletions are the likely result of "" extra ÏÏ mixing (cool bottom processing). The origin of the 18O enrichments in Group 4 grains is unknown, but it might be due to initial compositional di †erences of the stellar sources or to unusual third dredge-up in lowmass AGB stars. The highly 17O-enriched grain T54 could have formed in an AGB star undergoing hot bottom burning or in a massive star in the Of-WN phase.O-rich circumstellar dust seems to be underrepresented in meteorites, relative to C-rich. Explanations include the possibility that most O-rich stardust grains are silicates and have been destroyed either in the laboratory or in nature and the possibility that presolar has a Ðner grain size distribution Al 2 O 3 than SiC and graphite.

We report the discovery of five SiC grains and one graphite grain isolated from the Murchison carbonaceous meteorite whose major-element isotopic compositions indicate an origin in nova explosions. The grains are characterized by low 12C/13C (4-9) and 14N/15N (5-20) ratios, large excesses in 30Si (30Si/28Si ratios range to 2.1 times solar) and high 26Al/27Al ratios. These isotopic signatures are theoretically predicted for the ejecta from ONe novae and cannot be matched by any other stellar sources. Previous studies of presolar grains from primitive meteorites have shown that the vast majority formed in red giant outflows and supernova ejecta. Although a classical nova origin was suggested for a few presolar graphite grains on the basis of 22Ne enrichments, this identification is somewhat ambiguous since it is based only on one trace element. Our present study presents the first evidence for nova grains on the basis of major element isotopic compositions of single grains. We also present the results of nucleosynthetic calculations of classical nova models and compare the predicted isotopic ratios with those of the grains. The comparison points toward massive ONe novae if the ejecta are mixed with material of close-to-solar composition.Comment: 20 pages, 5 figures, 1 table. ApJ, in pres

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