SUMMARY Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.

We report first results from a large project to measure black hole (BH) mass in high accretion rate active galactic nuclei (AGNs). Such objects may be different from other AGNs in being powered by slim accretion disks and showing saturated accretion luminosities, but both are not yet fully understood. The results are part of a large reverberation mapping (RM) campaign using the 2.4-m Shangri-La telescope at the Yunnan Observatory in China. The goals are to investigate the gas distribution near the BH and the properties of the central accretion disks, to measure BH mass and Eddington ratios, and to test the feasibility of using such objects as a new type of cosmological candles. The paper presents results for three objects, Mrk 335, Mrk 142 and IRAS F12397+3333 with Hβ time lags relative to the 5100Å continuum of 10.6 +1.7 −2.9 , 6.4 +0.8 −2.2 and 11.4 +2.9 −1.9 days, respectively. The corresponding BH masses are (8.3 +2.6 −3.2 ) × 10 6 M ⊙ , (3.4 +0.5 −1.2 ) × 10 6 M ⊙ and (7.5 +4.3 −4.1 ) × 10 6 M ⊙ , and the lower limits on the Eddington ratios 0.6, 2.3, and 4.6 for the minimal radiative efficiency of 0.038. Mrk 142 and IRAS F12397+333 (extinction corrected) clearly deviate from the currently known relation between Hβ lag and continuum luminosity. The three Eddington ratios are beyond the values expected in thin accretion disks and two of them are the largest measured so far among objects with RM-based BH masses. We briefly discuss implications for slim disks, BH growth and cosmology.

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We have completed two years of photometric and spectroscopic monitoring of a large number of active galactic nuclei (AGNs) with very high accretion rates. In this paper, we report on the result of the second phase of the campaign, during 2013-2014, and the measurements of five new Hβ time lags out of eight monitored AGNs. All five objects were identified as super-Eddington accreting massive black holes (SEAMBHs). The highest measured accretion rates for the objects in this campaign areṀ 200, wherė M =Ṁ • /L Edd c −2 ,Ṁ • is the mass accretion rates, L Edd is the Eddington luminosity and c is the speed of light. We find that the Hβ time lags in SEAMBHs are significantly shorter than those measured in sub-Eddington AGNs, and the deviations increase with increasing accretion rates. Thus, the relationship between broad-line region size (R Hβ ) and optical luminosity at 5100Å, R Hβ − L 5100 , requires accretion rate as an additional parameter. We propose that much of the effect may be due to the strong anisotropy of the emitted slim-disk radiation. Scaling R Hβ by the gravitational radius of the black hole, we define a new radius-mass parameter (Y ) and show that it saturates at a critical accretion rate ofṀ c = 6 ∼ 30, indicating a transition from thin to slim accretion disk and a saturated luminosity of the slim disks. The parameter Y is a very useful probe -2for understanding the various types of accretion onto massive black holes. We briefly comment on implications to the general population of super-Eddington AGNs in the universe and applications to cosmology.

As one of the series of papers reporting on a large reverberation mapping campaign of super-Eddington accreting massive black holes (SEAMBHs) in active galactic nuclei (AGNs), we present the results of 10 SEAMBHs monitored spectroscopically during 2015-2017. Six of them are observed for the first time, and have generally higher 5100Å luminosities than the SEAMBHs monitored in our campaign from 2012 to 2015; the remaining four are repeat observations to check if their previous lags change. Similar to the previous SEAMBHs, the Hβ time lags of the newly observed objects are shorter than the values predicted by the canonical R Hβ -L 5100 relation of sub-Eddington AGNs, by factors of ∼ 2 − 6, depending on the accretion rate. The four previously observed objects have lags consistent with previous measurements. We provide linear regressions for the R Hβ -L 5100 relation, solely for the SEAMBH sample and for low-accretion AGNs. We find that the relative strength of Fe II and the profile of the Hβ emission line can be used as proxies of accretion rate, showing that the shortening of Hβ lags depends on accretion rates. The recent SDSS-RM discovery of shortened Hβ lags in AGNs with low accretion rates provides compelling evidence for retrograde accretion onto the black hole. These evidences show that the canonical R Hβ -L 5100 relation holds only in AGNs with moderate accretion rates. At low accretion rates, it should be revised to include the effects of black hole spin, whereas the accretion rate itself becomes a key factor in the regime of high accretion rates.

The radius-luminosity (R Hβ -L 5100 ) relationship of active galactic nuclei (AGNs) established by the reverberation mapping (RM) observations has been widely used as a single-epoch black hole mass estimator in the research of large AGN samples. However, the recent RM campaigns discovered that the AGNs with high accretion rates show shorter time lags by factors of a few comparing with the predictions from the R Hβ -L 5100 relationship. The explanation of the shortened time lags has not been finalized yet. We collect 8 different singleepoch spectral properties to investigate how the shortening of the time lags correlate with those properties and to understand what is the origin of the shortened lags. We find that the flux ratio between Fe II and Hβ emission lines shows the most prominent correlation, thus confirm that accretion rate is the main driver for the shortened lags. In addition, we establish a new scaling relation including the relative strength of Fe II emission. This new scaling relation can provide less biased estimates of the black hole mass and accretion rate from the single-epoch spectra of AGNs.

This is the third in a series of papers reporting on a large reverberation-mapping campaign aimed to study the properties of active galactic nuclei (AGNs) with high accretion rates. We present new results on the variability of the optical Fe II emission lines in 10 AGNs observed by the Yunnan Observatory 2.4 m telescope from2012 to2013. We detect statistically significant timelags, relative to the AGN continuum, in nine of the sources. This accurate measurement is achieved using a sophisticated spectral fitting scheme that allows for apparent flux variations of the host galaxy, and several narrowlines, due to the changing observing conditions. Six of the newly detected lags are indistinguishable from the Hβ lags measured in the same sources. Two are significantly longer and one is slightly shorter. Combining these findings with the Fe II lags reported in previous studies, we find an Fe II radius-luminosity relationship similar to the one for Hβ, although our sample by itself shows no clear correlation. The results support the idea that Fe II emission lines originate in photoionized gas, which, for the majority of the newly reported objects, is indistinguishable from the Hβ-emitting gas. We also present a tentative correlation between the lag and intensity of Fe II and Hβ and comment on its possible origin.

This is the second in a series of papers reporting on a large reverberation mapping (RM) campaign to measure black hole (BH) mass in high accretion rate active galactic nuclei (AGNs). The goal is to identify super-Eddington accreting massive black holes (SEAMBHs) and to use their unique properties to construct a new method for measuring cosmological distances. Based on theoretical models, the saturated bolometric luminosity of such sources is proportional to the BH mass which can be used to obtain their distance. Here we report on five new RM measurements and show that in four of the cases we can measure the BH mass and three of these sources are SEAMBHs. Together with the three sources from our earlier work, we now have six new sources of this type. We use a novel method based on a minimal radiation efficiency to identify nine additional SEAMBHs from earlier RM-based mass measurements. We use a Bayesian analysis to determine the parameters of the new distance expression, and the method uncertainties, from the observed properties of the objects in the sample. The ratio of the newly measured distances to the standard cosmological ones has a mean scatter of 0.14 dex, indicating that SEAMBHs can be use as cosmological distance probes. With their high luminosity, long period of activity and large numbers at high redshifts, SEAMBHs have a potential to extend the cosmic distance ladder beyond the range now explored by type Ia supernovae.