Search Results (26)

Zika virus (ZIKV), a unique flavivirus with neurotropic and teratogenic potential, can cross the blood–brain barrier and persist in human brain microvascular endothelial cells (BMECs); however, no approved vaccines or specific antivirals exist, and its barrier-crossing and neuroinvasive mechanisms remain elusive. Innovative strategies to identify additional host factors mediating ZIKV infection could yield key insights and help address these challenges. To uncover novel host factors, we established the first tree shrew (Tupaia belangeri) genome-wide CRISPR/Cas9 knockout (GeCKO) library and performed a screen in BMECs, identifying ring finger protein 6 (RNF6) as a novel proviral factor for ZIKV. ZIKV infection in BMECs was significantly reduced following RNF6 knockout or knockdown but enhanced upon RNF6 overexpression or rescue. Mechanistically, RNF6 interacts with the ZIKV NS5 protein and acts as a potential negative regulator of the type I interferon and MAPK signaling pathways. Evolutionary and structural analyses revealed that RNF6 is highly conserved between humans and tree shrews; molecular docking further identified shared NS5-binding residues (Gln-59, Arg-140), supporting the conserved proviral role of human RNF6 in ZIKV infection. Our findings highlight tree shrew GeCKO screening as an efficient approach for identifying novel host factors and establish RNF6 as a critical proviral factor for ZIKV replication in BMECs, providing new insights into ZIKV neurotropic pathogenesis and informing potential antiviral strategies. Full article

Hepatitis viruses continue to pose major global health challenges, necessitating the development of reliable and well-characterized experimental models. Tree shrews are increasingly recognized as a valuable small animal model because of their natural susceptibility to hepatitis viruses and close phylogenetic relationship with primates. Recent identification of a high prevalence of natural hepacivirus infections in tree shrews underscores the urgent need for routine viral screening of the animals used in hepatitis studies. Undetected infections may confound experimental results, undermine data integrity, and pose risks to laboratory biosecurity. Integrating systematic screening and standardized reporting practices will minimize these risks, enhance reproducibility, and safeguard the integrity of research findings. Moreover, a consistent assessment of the infection status will enhance the translational potential of tree shrews for studying viral hepatitis pathogenesis and evaluating antiviral interventions. This opinion paper emphasizes that ensuring the virological status of tree shrews is not merely a procedural recommendation but also a methodological standard essential for advancing hepatitis virus research. Full article

Hepatitis E, caused by the hepatitis E virus (HEV), is a zoonotic disease that extends beyond hepatocellular necrosis to replicate in multiple organs. While most infections are self-limiting, HEV infection during pregnancy is associated with severe outcomes, including acute liver failure, preterm delivery, and miscarriage, with the mechanisms underlying this high pathogenicity remaining poorly understood. This study established a pregnant tree shrew model with a late-stage HEV infection and a cellular model using zoonotic HEV genotypes GT3 and GT4 to investigate the effects of estrogen on HEV replication. Results showed that negative-strand RNA detection revealed replicative intermediates in feces and tissues during the acute phase, with peak viral loads occurring within one week and the highest titers in bile. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels rose at 3 days post-inoculation (DPI), peaking at 7 DPI. Elevated estrogen levels post-miscarriage correlated with increased viral loads, a trend mirrored in cell culture models showing linear relationships between estrogen and viral replication. Histopathology demonstrated viral hepatitis lesions in liver tissues and abnormalities in the uterus, ovaries, and brain, including hydropic degeneration, neuronal disruption, and granulosa cell necrosis. This study developed a pregnant tree shrew model for HEV infection, providing a robust tool for exploring pathogenic mechanisms during pregnancy and genotype-specific differences in zoonotic HEV pathogenicity. These findings offer new insights into the role of estrogen in HEV replication and its contribution to adverse pregnancy outcomes. Full article

The Chattogram Hill Tracts (CHTs) in Bangladesh have a rich biodiversity, hosting a wide range of wild mammal species, underscoring the importance of systematic monitoring focused on conservation efforts. This study aims to assess the diversity and abundance of small- and medium-sized wild mammal species in Pittachhara Forest in the CHTs. A comprehensive wildlife monitoring survey was conducted in this forest using strategically placed camera traps to identify the wild species diversity, and we evaluated the activity patterns and seasonal variations for the period of February 2023 to August 2024. The camera trap identified eight species of small- and medium-sized wild mammals: the Bengal slow loris, northern pig-tailed macaque, leopard cat, large Indian civet, common palm civet, crab-eating mongoose, northern tree shrew, and black rat. The activity patterns showed distinct temporal behaviors among these wild mammals, with nocturnal activity dominating for the Bengal slow loris and leopard cat, while the northern pig-tailed macaque exhibited diurnal activity. Seasonal variations demonstrated a significant difference in increased activity among most wild mammal species throughout the summer, particularly the large Indian civet and crab-eating mongoose, likely due to favorable environmental conditions, and decreased activity in the winter (p < 0.05). The findings suggest an intricate connection between species-specific behaviors and environmental factors that influence activity patterns, with increased activity in summer and a decrease in winter, indicating that summer conditions may enhance the movement and foraging behaviors of mammals. This study underscores the necessity for continuous biodiversity monitoring followed by conservation efforts in Pittachhara Forest to reduce the threats of habitat fragmentation, human disturbances, and inadequate protection, thus protecting the survival of endangered wild mammal species and maintaining the environmental harmony of this small, protected area. Full article

Chiggers (chigger mites) are a group of tiny arthropods, and they are the exclusive vector of Orientia tsutsugamushi (Ot), the causative agent of scrub typhus (tsutsugamushi disease). Dehong Prefecture in Yunnan Province of southwest China is located on the China–Myanmar border and is an important focus of scrub typhus. Based on the field surveys in Dehong between 2008 and 2022, the present paper reports the infestation and ecological distribution of chiggers on the body surface of rodents and other sympatric small mammals (shrews, tree shrews, etc.) in the region for the first time. The constituent ratio (C_r), prevalence (P_M), mean abundance (MA), and mean intensity (MI) were routinely calculated to reflect the infestation of small-mammal hosts with chiggers. Additionally, the species richness (S), Shannon–Wiener diversity index (H), Simpson dominance index (D), and Pielou’s evenness index (E) were calculated to illustrate the chigger community structure. Preston’s log-normal model was used to fit the theoretical curve of species abundance distribution, and the Chao 1 formula was used to roughly estimate the expected total species. The “corrplot” package in R software (Version 4.3.1) was used to analyze interspecific relationships, and the online drawing software was used to create a chord diagram to visualize the host–chigger associations. From 1760 small-mammal hosts, a total of 9309 chiggers were identified as belonging to 1 family, 16 genera, and 117 species, with high species diversity. The dominant chigger species were Leptotrombidium deliense, Walchia ewingi, and Gahrliepia longipedalis, with a total C_r = 47.65% (4436/9309), among which L. deliense is the most important vector of Ot in China. The overall infestation indexes (P_M, MA, and MI) and community parameters (S, H, and E) of chiggers in the mountainous areas and outdoors were higher than those in the flatland areas and indoors, with an obvious environmental heterogeneity. Leptotrombidium deliense was the dominant species in the flatland and indoors, while G. longipedalis was the prevalent species in the mountainous and outdoor areas. The species abundance distribution of the chigger community conformed to log-normal distribution with the theoretical curve equation: ${S\left(R\right)}^{\prime }=28e^{{-[0.23(R-0)]}^2}$, indicating the existence of many rare species and only a few dominant species in the community. The expected total number of chigger species was roughly estimated to be 147 species, 30 more than the 117 species actually collected, suggesting that some uncommon species may have been missed in the sampling survey. The host–parasite association analysis revealed that one host species can harbor different chigger species, and one chigger species can parasitize different host species with low host specificity. A positive or negative correlation existed among different chigger species, indicating a cooperative or competitive interspecific relationship. The species diversity of chiggers is high in Dehong on the China–Myanmar border, and a large host sample is recommended to find more uncommon species. There is an obvious environmental heterogeneity of the chigger community, with different species diversity and dominant species in different environments. The low host specificity of chiggers and the occurrence of a large number of L. deliense in Dehong, especially in flatland areas and indoors, would increase the risk of persistent transmission of scrub typhus in the region. Full article

Wildlife crossings are implemented in many countries to facilitate the dispersal of animals among habitats fragmented by roads. However, the efficacy of different types of habitat corridors remains poorly understood. We used a comprehensive sampling regime in two lowland dipterocarp forest areas in peninsular Malaysia to sample pairs of small mammal individuals in three treatment types: (1) viaduct sites, at which sampling locations were separated by a highway but connected by a vegetated viaduct; (2) non-viaduct sites, at which sampling locations were separated by a highway and not connected by a viaduct; and (3) control sites, at which there was no highway fragmenting the forest. For four small mammal species, the common tree shrew Tupaia glis, Rajah’s spiny rat Maxomys rajah, Whitehead’s spiny rat Maxomys whiteheadi and dark-tailed tree rat Niviventer cremoriventer, we used genome-wide markers to assess genetic diversity, gene flow and genetic structure. The differences in genetic distance across sampling settings among the four species indicate that they respond differently to the presence of highways and viaducts. Viaducts connecting forests separated by highways appear to maintain higher population connectivity than forest fragments without viaducts, at least in M. whiteheadi, but apparently not in the other species. Full article

The p53 protein is a transcriptional regulatory factor and many of its functions require that it forms a tetrameric structure. Although the tetramerization domain of mammalian p53 proteins (p53TD) share significant sequence similarities, it was recently shown that the tree shrew p53TD is considerably more thermostable than the human p53TD. To determine whether other mammalian species display differences in this domain, we used biophysical, functional, and structural studies to compare the properties of the p53TDs from six mammalian model organisms (human, tree shrew, guinea pig, Chinese hamster, sheep, and opossum). The results indicate that the p53TD from the opossum and tree shrew are significantly more stable than the human p53TD, and there is a correlation between the thermostability of the p53TDs and their ability to activate transcription. Structural analysis of the tree shrew and opossum p53TDs indicated that amino acid substitutions within two distinct regions of their p53TDs can dramatically alter hydrophobic packing of the tetramer, and in particular substitutions at positions corresponding to F341 and Q354 of the human p53TD. Together, the results suggest that subtle changes in the sequence of the p53TD can dramatically alter the stability, and potentially lead to important changes in the functional activity, of the p53 protein. Full article

Background: The characteristics of glioblastoma, such as drug resistance during treatment, short patient survival, and high recurrence rates, have made patients with glioblastoma more likely to benefit from oncolytic therapy. Methods: In this study, we investigated the safety of the sindbis virus by injecting virus intravenously and intracranially in mice and evaluated the therapeutic effect of the virus carrying different combinations of IL-12, IL-7, and GM-CSF on glioma in a glioma-bearing mouse model. Results: SINV was autologously eliminated from the serum and organs as well as from neural networks after entering mice. Furthermore, SINV was restricted to the injection site in the tree shrew brain and did not spread throughout the whole brain. In addition, we found that SINV-induced apoptosis in conjunction with the stimulation of the immune system by tumor-killing cytokines substantially suppressed tumor development. It is worth mentioning that SINV carrying IL-7 and IL-12 had the most notable glioma-killing effect. Furthermore, in an intracranial glioma model, SINV containing IL-7 and IL-12 effectively prolonged the survival time of mice and inhibited glioma progression. Conclusions: These results suggest that SINV has a significant safety profile as an oncolytic virus and that combining SINV with cytokines is an efficient treatment option for malignant gliomas. Full article

The Indian highland shrew, Suncus niger (Horsfield, 1851), is the least studied soricid species from its original range distribution in Southern India, with several systematics conundrums. Following its discovery in 1851, the species was synonymized with Suncus montanus (Kelaart, 1850) (endemic to Sri Lanka) and subsequently identified as a separate Indian population. However, the systematic status of S. niger from topotype specimens in Southern India has yet to be determined through an integrated approach. Both taxonomy and mitochondrial genetic data (Cytochrome b and 16S ribosomal RNA) were used to re-examine the systematics of S. niger. The mtCytb gene clearly distinguished topotypic S. niger from other Suncus species, with high genetic divergences varying from 8.49% to 26.29%. Further, the Bayesian and maximum likelihood topologies clearly segregated S. niger from other congeners and corroborated the sister relationship with S. stoliczkanus with expected divergence in the late Pliocene (2.62 MYA). The TimeTree analysis also exhibits a strong matrilineal affinity of S. dayi (endemic to India) toward the African species. The current study hypothesizes that the ancestor of the soricids evolved in Africa and that genetic lineages were subsequently shifted by plate tectonic events that subsequently colonized different continents as distinct species during the late Miocene (Tortonian) to the Holocene era. In addition to the new range expansion and elevation records of S. niger in the Central Western Ghats, we propose that additional sampling across its distribution, as well as the use of multiple genetic markers, may be useful in determining the genetic diversity and population structure of this endemic species. The present study also recommends that more molecular data on the Soricomorphs lineages, and estimates of their divergence times, will shed light on the evolution of these small mammals on Earth. Full article

The lens mitochondrion of the tree shrew, located along the optical pathway between the lens and photoreceptors, has been investigated. The results suggest that the lens mitochondrion acts as a quasi-bandgap or imperfect photonic crystal. Interference effects cause a shift in the focus and introduce wavelength-dependent behavior similar to dispersion. Optical channels within the mitochondrion form a mild waveguide, preferentially propagating light within certain compartments. The lens mitochondrion also functions as an imperfect UV-shielding interference filter. Overall, this study provides insights into the dual role of the lens mitochondrion and the complex behavior of light within biological systems. Full article

The function and regulation of rapid-eye-movement (REM) sleep is a topic of ongoing debate. It is often assumed that REM sleep is a homeostatically regulated process and that a need for REM sleep builds up, either during prior wakefulness or during preceding slow wave sleep. In the current study, we tested this hypothesis in six diurnal tree shrews (Tupaia belangeri), small mammals closely related to primates. All animals were individually housed and kept under a 12:12 light-dark cycle with an ambient temperature of 24 °C. We recorded sleep and temperature in the tree shrews for 3 consecutive 24 h days. During the second night, we exposed the animals to a low ambient temperature of 4 °C, a procedure that is known to suppress REM sleep. Cold exposure caused a significant drop in brain temperature and body temperature and also resulted in a strong and selective suppression of REM sleep by 64.9%. However, contrary to our expectation, the loss of REM sleep was not recovered during the subsequent day and night. These findings in a diurnal mammal confirm that the expression of REM sleep is highly sensitive to environmental temperature but do not support the view that REM sleep is homeostatically regulated in this species. Full article

Physical obstacles within animal habitats create barriers to individual movements. To cross those barriers, specific corridors are used, some of them created by keystone species such as Eurasian beavers (Castor fiber). Their dams on rivers may also increase habitat connectivity for terrestrial mammals, but the significance of that function has never been quantified. To investigate this, we placed tracking tunnels on beaver dams, fallen trees, and—as a control—on floating rafts. Additionally, we tested kinetic sand as a novel substrate for collecting tracks and found the paws of small mustelids precisely imprinted in that medium, allowing easy identification. However, we needed to lump all shrews and rodents smaller than water voles (Arvicola amphibius) into one category as they can only be detected but not identified. The highest mammalian activity was observed on dams, as they may provide shelter, offering protection from predators during a river crossing or permanent residence, and even the opportunity to hunt invertebrates. Slightly higher diversity was found on logs because of a higher proportion of mustelids, which select exposed locations for scent marking. Our results increase our body of knowledge about the beaver as an ecosystem engineer and provide a novel tool for the monitoring of mammal activity. Full article

Many human clinical cases attributed to vector-borne pathogens are underreported in Malaysia, especially in rural localities where healthcare infrastructures are lacking. Here, 217 small mammals, consisting of rodents and tree shrews, were trapped in oil palm plantations in the Peninsular Malaysia states of Johor and Perak. Species identification was performed using morphological and DNA barcoding analyses, and 203 small mammals were included in the detection of selected vector-borne bacteria. The DNA extracted from the spleens was examined for Orientia tsutsugamushi, Borrelia spp., Bartonella spp. and Rickettsia spp. using established PCR assays. The small mammals collected in this study included Rattus tanezumi R3 mitotype (n = 113), Rattus argentiventer (n = 24), Rattus tiomanicus (n = 22), Rattus exulans (n = 17), Rattus tanezumi sensu stricto (n = 1) and Tupaia glis (n = 40). Orientia tsutsugamushi, Borrelia spp. and Bartonella phoceensis were detected in the small mammals with the respective detection rates of 12.3%, 5.9% and 4.9%. Rickettsia spp., however, was not detected. This study encountered the presence of both Lyme disease and relapsing fever-related borreliae in small mammals collected from the oil palm plantation study sites. All three microorganisms (Orientia tsutsugamushi, Borrelia spp. and Bartonella phoceensis) were detected in the R. tanezumi R3 mitotype, suggesting that the species is a competent host for multiple microorganisms. Further investigations are warranted to elucidate the relationships between the ectoparasites, the small mammals and the respective pathogens. Full article

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews. Full article

The putamen (Put) is necessary for habitual actions, while the nucleus caudate (Cd) is critical for goal-directed actions. However, compared with the natural reward (such as sucrose)-seeking habit, how drug-related dysfunction or imbalance between the Put and Cd is involved in cocaine-seeking habit, which is not easy to bias behavior to goal-directed actions, is absent. Therefore, in our present study, in comparison with sucrose-habitual behavior, we evaluated the distinctive changes of the two subtypes of dopamine (DA) receptors (D1R and D2R) in cocaine-seeking habitual behavior animals. Moreover, the adaptive changes of Ca_v1.2 and Ca_v1.3, as prime downstream targets of D1R and D2R respectively, were also assessed. Our results showed that a similar percentage of the animals exhibited habitual seeking behavior after cocaine or sucrose variable-interval self-administration (SA) training in tree shrews. In addition, compared with animals with non-habitual behavior, animals with cocaine habitual behavior showed higher D1Rs and Ca_v1.2 expression in the Put accompanied with lower D2Rs and Ca_v1.3 expression in the Cd. However, after sucrose SA training, animals with habitual behavior only showed lower membrane expression of D2R in the Put than animals with non-habitual behavior. These results suggested that the upregulation of D1Rs-Ca_v1.2 signaling may lead to hyper-excitability of the Put, and the inactivation of D2Rs-Ca_v1.3 signaling may result in depressed activity in the Cd. This imbalance function between the Put and Cd, which causes an inability to shift between habits and goal-directed actions, may underlie the compulsive addiction habit. Full article