Henipaviruses (HNV), Hendra (HeV) and Nipah (NiV) virus, cause severe pulmonary and neurologic disease in humans and other mammals. Bats in the genus Pteropus naturally host HeV and NiV, but their feasibility in experimental studies is limited due to their large size, low fertility rate, and unavailability outside of their native range. Understanding bat-henipavirus interactions that regulate shedding and replication could improve mitigation of spillover events and illuminate the factors that differentiate severe and controlled HNV infection. Here, we assessed the suitability of the Jamaican fruit bat (JFB) (Artibeus jamaicensis) to model HNV infection in vitro and in vivo. JFB primary kidney cells were permissive to HNVs, and HeV and NiV antagonized the induction of the innate antiviral response. JFBs were inoculated via the intranasal and oral routes (IN/PO) with HeV or NiV or intravenously (IV) with HeV and monitored for 7 days. Following IN/PO exposure, infection was quenched rapidly and limited HeV RNA was detected in oral swabs and tissues while NiV RNA was found in only one oral swab. HeV IV inoculation resulted in robust, disseminated infection and viral RNA was detected in oral, rectal, and environmental swabs. Overall, these results support that JFBs are susceptible to both viruses, but replication is quenched rapidly in vivo following IN/PO exposure. Future studies will optimize the in vivo model to leverage the JFB to further our understanding of bat-henipavirus interactions.

The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the U.S. poses a significant public health threat. To date, 70 human cases have been confirmed in the United States, including two severe cases and one fatality. While suitable animal models are crucial for predicting the potential pandemic risk of newly emerging pathogens in humans, studies investigating contemporary HPAIV H5N1 transmission dynamics remain limited. Here, we investigate the pathogenicity and transmission efficiency of recent clade 2.3.4.4b H5N1 viruses isolated from a bovine, mountain lion, and a human case using Syrian hamsters. Intranasal inoculation results in productive virus replication in the respiratory tract and shedding for all three isolates. Transmission studies demonstrate limited efficiency via direct contact and airborne routes for all isolates. Although overall transmission is inefficient, the human H5N1 isolate demonstrates relatively greater contact transmissibility than the bovine and mountain lion isolates. Taken together, our findings demonstrate that the Syrian hamster model complements existing animal models for influenza A virus research and expands the resources available for investigating the pathogenicity, transmissibility, and efficacy of countermeasures against HPAIV H5N1.

Vaccines against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are highly effective in preventing severe disease but are less consistent in protecting against infection and transmission. Developing vaccines with enhanced immunogenicity that can provide protection in both the upper and lower respiratory tract (URT and LRT) is crucial. Mucosal immunization induces immunity at the site of initial infection, the respiratory tract, thereby preventing or mitigating infection. Here, we compared immune responses elicited by intramuscular mRNA vaccination alone with those elicited by intramuscular mRNA vaccination followed by intranasal administration of ChAdOx1 nCoV-19 vaccine in mice. Although both vaccination strategies induced strong systemic immunity, robust humoral and cellular mucosal immune responses, including spike-specific IgA and tissue-resident T cells, were only detected upon mucosal vaccination. Compared to unvaccinated animals, mucosal vaccination resulted in migration of T cells and macrophages into the nasal turbinates, as well as migration and proliferation of B and T cells in the nasal-associated lymphoid tissue. While both vaccination regimens provided protection across the entire respiratory tract at 2 weeks post-vaccination, at 12 weeks post-vaccination, only the mice that received a mucosal vaccination remained protected in the URT. Gene-expression profiling of the respiratory tract at 2 days post-infection revealed distinct clustering between groups. Enrichment of immune signaling pathways, including B and T cells receptor pathways, was significantly higher in intranasally vaccinated animals. Together, our study demonstrates that mucosal vaccination provides durable protection against SARS-CoV-2 than intramuscular vaccination alone.

Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we model filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. Infection with EBOV results in systemic virus replication and oral shedding of infectious virus. MARV replication is transient and does not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induces innate antiviral responses that EBOV efficiently suppresses. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrate an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells.

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.

In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection via aerosols was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism.

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.

Differential methylation and histone marks upon 5-azacitidine treatment around 5mC-regulated genes

Extended investigation of the combination of 5-azacitidine and PRC inhibitors

The Omicron BA.1 variant of SARS-CoV-2 displays an attenuated phenotype in the Syrian hamster after intranasal inoculation. This is characterized by reduced viral replication and lung pathology in the lower respiratory tract. Here, we report that intratracheal inoculation with Omicron BA.1 recovers the lower respiratory tract replication and pathogenicity as observed with other lineages.

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24–48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1–10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0–100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24–48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

Graphical representation of adaptive epigenome reprogramming upon 5-azacitidine treatment in BRAFV600E CRC

Limited impact of 5-azacitidine treatment in gene expression changes

Psychology is a young science. Its definition and scope have shifted over the discipline’s short history. Here, we call for psychology to become a historical and geographical science. We list four underlying reasons as to why such a transformation, a chronospatial revolution, has yet to take off: problems in data, scope, synergy, and theory. We discuss the need for psychology to adopt a more holistic lens—one that incorporates the rich mosaic of shared history, the dynamism of cultural shifts, and the variations ingrained by ecology and cross-regional differences. Such an integrated approach not only enriches our microscopic understanding of Homo sapiens but also draws a more telescopic map of human psychology that encapsulates the human journey.

In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease. ### Competing Interest Statement The authors have declared no competing interest.

Several human respiratory viruses display a clear seasonal pattern with a higher incidence in the winter season in temperate regions. We previously determined that SARS-CoV-2 is more stable at low-temperature and low-humidity conditions compared to warmer temperature and higher-humidity. To determine if this translates into differential airborne transmission rates in vivo, we performed airborne transmission experiments in the Syrian hamster model under three different environmental conditions (10 °C, 45% relative humidity (RH), 22 °C, 45% RH, and 27 °C, 65% RH). We compared the ancestral SARS-CoV-2 Lineage A with the more transmissible Delta Variant of Concern (VOC). Airborne transmission was evaluated using SARS-CoV-2 infected donor animals at 24 h post inoculation. Sentinels were placed at a 90 cm distance in a transmission set-up and exposed for 1-h to infected donor animals. While environmental conditions moderately impacted lung RNA titers, the shedding kinetics of the donors were not affected by the environmental conditions and did not differ significantly between variants on day 1. Overall, the highest transmission efficiency was observed at 22 °C, 40%RH for Delta (62.5%, based on seroconversion), and ranged between 37.5 and 50% for all other conditions. However, these differences were not significant. To elucidate this further, we performed aerosol stability comparisons and found that infectious virus remained stable during a 1-h time window across all conditions. Our data suggest that even when environmental conditions affect the stability of SARS-CoV-2, this may not directly be translatable to measurable impacts on transmission in an experimental setting when exposure time is restricted.

Mutation and characteristics of conventional and PDX-derived CRC cell lines

Chromatin state profiles of control and 5-azacitidine-treated samples

Combining anti-EGFR antibodies did not improve response to vemurafenib plus 5-azacitidine treatment.

Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species in both Chiropteran suborders host filoviruses, suggesting that bats may have coevolved with this viral family. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we modelled filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis. Bats were inoculated with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. EBOV-infected bats supported systemic virus replication and shed infectious virus orally. In contrast, MARV replicated only transiently and was not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induced innate antiviral responses that EBOV efficiently suppressed. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrated an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells. ### Competing Interest Statement The authors have declared no competing interest.