Description: Subclinical viral infections (SVI), including cytomegalovirus (CMV), are highly prevalent in humans, resulting in lifelong persistence. However, the impact of SVI on the interplay between the host immunity and gut microbiota in the context of environmental exposures is not well defined. We utilized the preclinical nonhuman primate (NHP) model consisting of SVI-free (specific-pathogen-free [SPF]) rhesus macaques and compared them to the animals with SVI (non-SPF) acquired through natural exposure and investigated the impact of SVI on immune cell distribution and function, as well as on gut microbiota. These changes were examined in animals housed in the outdoor environment compared to the controlled indoor environment. We report that SVI are associated with altered immune cell subsets and gut microbiota composition in animals housed in the outdoor environment. Non-SPF animals harbored a higher proportion of potential butyrate-producing Firmicutes and higher numbers of lymphocytes, effector T cells, and cytokine-producing T cells. Surprisingly, these differences diminished following their transfer to the controlled indoor environment, suggesting that non-SPFs had increased responsiveness to environmental exposures. An experimental infection of indoor SPF animals with CMV resulted in an increased abundance of butyrate-producing bacteria, validating that CMV enhanced colonization of butyrate-producing commensals. Finally, non-SPF animals displayed lower antibody responses to influenza vaccination compared to SPF animals. Our data show that subclinical CMV infection heightens host immunity and gut microbiota changes in response to environmental exposures. This may contribute to the heterogeneity in host immune response to vaccines and environmental stimuli at the population level. IMPORTANCE Humans harbor several latent viruses that modulate host immunity and commensal microbiota, thus introducing heterogeneity in their responses to pathogens, vaccines, and environmental exposures. Most of our understanding of the effect of CMV on the immune system is based on studies of children acquiring CMV or of immunocompromised humans with acute or reactivated CMV infection or in ageing individuals. The experimental mouse models are genetically inbred and are completely adapted to the indoor laboratory environment. In contrast, nonhuman primates are genetically outbred and are raised in the outdoor environment. Our study is the first to report the impact of long-term subclinical CMV infection on host immunity and gut microbiota, which is evident only in the outdoor environment but not in the indoor environment. The significance of this study is in highlighting the impact of SVI on enhancing host immune susceptibility to environmental exposures and immune heterogeneity.

Description: Coxiella burnetii , the etiological agent of Q fever in humans, is an intracellular pathogen that replicates in an acidified parasitophorous vacuole derived from host lysosomes. Generation of this replicative compartment requires effectors delivered into the host cell by the Dot/Icm type IVb secretion system. Several effectors crucial for C. burnetii intracellular replication have been identified, but the host pathways coopted by these essential effectors are poorly defined, and very little is known about how spacious vacuoles are formed and maintained. Here we demonstrate that the essential type IVb effector, CirA, stimulates GTPase activity of RhoA. Overexpression of CirA in mammalian cells results in cell rounding and stress fiber disruption, a phenotype that is rescued by overexpression of wild-type or constitutively active RhoA. Unlike other effector proteins that subvert Rho GTPases to modulate uptake, CirA is the first effector identified that is dispensable for uptake and instead recruits Rho GTPase to promote biogenesis of the bacterial vacuole. Collectively our results highlight the importance of CirA in coopting host Rho GTPases for establishment of Coxiella burnetii infection and virulence in mammalian cell culture and mouse models of infection.

Description: Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a membrane-bound vacuole termed the inclusion. Early in the infection cycle, the pathogen extensively modifies the inclusion membrane through incorporation of numerous type III secreted effector proteins, called inclusion membrane proteins (Incs). These proteins are characterized by a bilobed hydrophobic domain of 40 amino acids. The presence of this domain has been used to predict up to 59 putative Incs for C. trachomatis ; however, localization to the inclusion membrane with specific antibodies has been demonstrated for only about half of them. Here, we employed recently developed genetic tools to verify the localization of predicted Incs that had not been previously localized to the inclusion membrane. Expression of epitope-tagged putative Incs identified 10 that were previously unverified as inclusion membrane localized and thus authentic Incs. One novel Inc and 3 previously described Incs were localized to inclusion membrane microdomains, as evidenced by colocalization with phosphorylated Src (p-Src). Several predicted Incs did not localize to the inclusion membrane but instead remained associated with the bacteria. Using Yersinia as a surrogate host, we demonstrated that many of these are not secreted via type III secretion, further suggesting they may not be true Incs. Collectively, our results highlight the utility of genetic tools for demonstrating secretion from chlamydia. Further mechanistic studies aimed at elucidating effector function will advance our understanding of how the pathogen maintains its unique intracellular niche and mediates interactions with the host.

Description: Infections with human coronavirus EMC (HCoV-EMC) are associated with severe pneumonia. We demonstrate that HCoV-EMC resembles severe acute respiratory syndrome coronavirus (SARS-CoV) in productively infecting primary and continuous cells of the human airways and in preventing the induction of interferon regulatory factor 3 (IRF-3)-mediated antiviral alpha/beta interferon (IFN-α/β) responses. However, HCoV-EMC was markedly more sensitive to the antiviral state established by ectopic IFN. Thus, HCoV-EMC can utilize a broad range of human cell substrates and suppress IFN induction, but it does not reach the IFN resistance of SARS-CoV.

Description: Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.

Description: Imaging the internal structure of faults remains challenging using conventional seismometers. Here, the authors use deployed fibre-optic cables to obtain strain data and identify faults and volcanic dykes in Iceland. Such fibre-optic networks are pervasive for telecommu-nication and could be used for hazard assessment. Natural hazard prediction and efficient crustal exploration requires dense seismic observa-tions both in time and space. Seismological techniques provide ground-motion data, whose accuracy depends on sensor characteristics and spatial distribution. In the manuscript Jousset et al. (2018), we demonstrate that strain determination is possible with conventional fibre-optic cables deployed for telecommunication. Extending recently distributed acoustic sensing (DAS) studies, we present high resolution spatially un-aliased broadband strain data. We recorded seismic signals from natural and man-made sources with 4-m spacing along a 15-km-long fibre-optic cable layout on Reykjanes Peninsula, SW Iceland.

Description: The SWATH-D experiment is dense deployment of 154 seismic stations in the Central and Eastern Alps between Italy and Austria, complementing the larger-scale sparser AlpArray Seismic Network (AASN). SWATH-D will provide high resolution images from the surface into the upper mantle, and allow observations of local seismicity. SWATH-D focuses on a key area of the Alps where the hypothesized flip in subduction polarity has been suggested, and where an earlier seismic profile (TRANSALP) has imaged a jump in the Moho. Where mains power is available (at ca. 80 sites) stations are providing realtime data via the cellphone network and are equipped with Güralp CMG-3EPSC (60s) seismometers and Earth Data Recorders EDR-210. The rest of the stations are offline and consist mainly of Nanometrics Trillium Compact (120s) and Güralp CMG-3EPSC (60s) seismometers equipped with either Omnirecs CUBE3 or PR6-24 Earth Data Loggers. All stations are equipped with external GPS antennas and the sampling rate is 100 Hz (Heit, et al., 2018). The network will operate for 2 years starting in July 2017. The Swath-D data will be used directly by 20 individual proposals of the MB-4D Priority Program (Mountain Building Processes in Four Dimensions, 2017) of the German Research Foundation (DFG) and data products derived from it will contribute to additional 13 proposals. SWATH-D is thus an important link between the MB-4D Priority Program and the international AlpArray communities and a scientific service to many of the proposals within the DFG Priority Program. Waveform data are available from the GEOFON data centre, under network code ZS, and are embargoed until August 2023. After the end of embargo, data will be openly available under CC-BY 4.0 license according to GIPP-rules.

Description: Dataset

Description: The KISS network was installed in the frame of the "Klyuchevskoy Investigation - Seismic Structure of an extraordinary volcanic system" project and recorded data between summer 2015 and summer 2016 in one of the world's largest clusters of subduction volcanoes - the Klyuchevskoy volcanic group (KVG). It is located in eastern Russia at the northern end of the Kuril-Kamchatka subduction zone close to its intersection with the Aleutian arc and the north-western termination of Hawaii-Emperor seamount chain. Additional to the 4700m high Mount Klyuchevskoy the KVG contains 12 other volcanoes that have together erupted about 1 cubic meter rock per second averaged over the past 10,000 years. Among those Klyuchevskoy, Bezymianny and Tolbachik were the most active ones during the last decades with eruptions styles ranging from explosive to Hawaiian-type. The KISS experiment is designed to investigate the volcanic and seismic processes and its structural setting in the KVG. The network covers a circular region of about 80km diameter with some linear extensions. It includes data from 77 temporary seismic stations with broadband and short period sensors that were installed on concrete plates in about 60cm deep holes. Due to the local conditions the stations were battery powered and could not be serviced during the experiment. GPS reception of the digitizers was not continuous at all stations due to thick snow cover and vegetation. Waveform data are available from the GEOFON data centre, under network code X9, and are embargoed until end of 2019.