ABSTRACT: A novel rabies virus was identified after death in a man who had immigrated from Oaxaca, Mexico, to California, USA. Despite the patient's history of exposure to domestic and wild carnivores, molecular and phylogenetic characterizations suggested that the virus originated from insectivorous bats. Enhanced surveillance is needed to elucidate likely reservoirs.
Project description:In the Western Hemisphere, bat-associated rabies viruses (RABVs) have established independent transmission cycles in multiple mammal hosts, forming genetically distinct lineages. In New Mexico, USA, skunks, bats, and gray foxes are rabies reservoir hosts and represent a public health risk because of encounters with humans. During 2015 and 2019, two previously undescribed RABVs were detected in 2 gray foxes (Urocyon cinereoargenteus) in Lincoln County, New Mexico. Phylogenetic analysis of the nucleoprotein gene indicated that the isolates are a novel RABV variant. These 2 cases probably represent repeated spillover events from an unknown bat reservoir to gray foxes. Molecular analysis of rabies cases across New Mexico identified that other cross-species transmission events were the result of viral variants previously known to be enzootic to New Mexico. Despite a robust rabies public health surveillance system in the United States, advances in testing and surveillance techniques continue to identify previously unrecognized zoonotic pathogens.
Project description:Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5'-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein-protein interaction with the cellular translation machinery.
Project description:The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant. Long-term levels of VNA could be elicited that remained greater than 0.5 IU per ml serum, indicative for the protective status. Single applications of higher doses (10(7) PFU) can be sufficient to confer complete protection against intracranial (i.c.) challenge, whereas booster immunization was needed for protection by the application of lower dosages. Anamnestic immune responses were achieved by each of the seven tested routes of inoculation, including oral application. Finally, in vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell subpopulations during immunization and/or challenge infection attested the importance of CD4 T cells for the induction of protective immunity by D1701-V-RabG. This report demonstrates another example of the potential of the ORFV vector and also indicates the capability of the new recombinant for vaccination of animals.
Project description:Information is scarce about sylvatic rabies virus in Asia and about rabies in palm civets. We report a novel sylvatic rabies virus variant detected in a golden palm civet in Sri Lanka. Evolutionary analysis suggests the virus diverged from canine rabies viruses in Sri Lanka in ≈1933 (range 1886-1963).
Project description:OBJECTIVES:Though previous research has indicated that language brokering can be stressful, the findings are mixed, pointing to potential moderators of the association. Guided by an ecological perspective, we examined the role of individual, family, and environmental factors in Mexican American adolescents' acute cortisol responses to language brokering. METHOD:The study consisted of 46 Mexican American adolescents recruited around a metropolitan city in Central Texas. Participants translated a difficult medical document from English to Spanish for their parents, followed by an arithmetic task (modeled after the Trier Social Stress Test [TSST]). Participants' perceptions (perceived efficacy and parental dependence), parental hostility, and discrimination experiences were assessed via self-report and were examined as moderators of adolescents' responses to the task. RESULTS:Results revealed differential responses to the task based on individual, family, and environmental factors. High efficacy and low dependence-parental hostility-discrimination related to stress responses characterized by low baselines, steeper reactivity, and faster recovery. Low efficacy and high dependence related to greater baseline stress and a slower recovery. High levels of parental hostility related to a slower recovery. High levels of discrimination related to greater baseline stress. CONCLUSIONS:The study demonstrates that the modified TSST task can elicit an acute hypothalamic-pituitary-adrenal axis response, but the nature of this response is dependent upon participants' perceptions of language brokering (parental dependence and efficacy), parental hostility, and discrimination experiences. Adolescents' individual characteristics and contextual demands remain important considerations in understanding their acute stress responses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Project description:Mokola virus (MOKV) is a rabies-related lyssavirus and appears to be exclusive to the African continent. Only 24 cases of MOKV, which includes two human cases, have been reported since its identification in 1968. MOKV has an unknown reservoir host and current commercial vaccines do not confer protection against MOKV.We describe three new isolations of MOKV from domestic cats in South Africa. Two cases were retrospectively identified from 2012 and an additional one in 2014.These cases emphasize the generally poor surveillance for rabies-related lyssaviruses and our inadequate comprehension of the epidemiology and ecology of Mokola lyssavirus per se.
Project description:Acetylation is the PTM that strongly interlinked with glucose metabolism, so we performed Liquid chromatography–mass spectrometry (LC-MS) to detect acetylated proteins in RABV-infected mouse brains to further investigate the reason how Rabies virus (RABV) infection promotes glucose uptake. To reveal the changes in lysine acetylation due to RABV infection, the brains of mice infected with different RABV strains were harvested for a quantitative proteomic assay.
Project description:Using the Los Angeles Family and Neighborhood Survey (L.A.FANS-2; n = 1610), we explore the link between Mexican immigrant acculturation, diet, exercise and obesity. We distinguish Mexican immigrants and 2nd generation Mexicans from 3rd+ generation whites, blacks and Mexicans. First, we examine variation in social and linguistic measures by race/ethnicity, duration of residence and immigrant generation. Second, we consider the association between acculturation, diet and exercise. Third, we evaluate the degree to which acculturation, diet, exercise, and socioeconomic status explain the association between race/ethnicity, immigrant exposure to the US (duration since immigration/generation), and adult obesity. Among immigrants, we find a clear relationship between acculturation measures, exposure to the US, and obesity-related behaviors (diet and exercise). However, the acculturation measures do not clearly account for the link between adult obesity, immigrant duration and generation, and race/ethnicity.
Project description:Rabies is a highly fatal non-suppurative encephalomyelitis, caused by the Rabies virus. Dogs are the major reservoir of rabies in India and are the source of infection to other domestic animals. In this report, laboratory investigation and molecular characterization of isolates from two cows with paralytic rabies is described. Necropsy brain samples from the two cows were tested for the presence of rabies antigen using a fluorescent antibody test and the results were confirmed using RT-PCR. Rabies virus was successfully isolated from both the brain samples in a murine neuroblastoma cell line. The phylogenetic analysis of partial nucleoprotein gene sequences of these isolates showed them to be of a variant of Rabies virus which is closely related to the Sri Lankan Rabies virus lineage as previously reported. In addition, partial nucleoprotein genes of 19 more Rabies virus isolates from southern India were sequenced and of these 11 isolates were found to be closely related to the Sri Lankan lineage. The deduced amino acid sequences of the partial nucleoprotein of the Indian isolates were 96-99% identical to the Sri Lankan isolates. This investigation re-confirms the previous speculations that the Sri Lankan variant of the virus may still be actively transmitted by animals in India.
Project description:In 1998, a varicella-zoster virus glycoprotein E (gE) mutant virus (VZV-MSP) was isolated from a child with chickenpox. VZV-MSP, representing a second VZV serotype, was considered a rarity. We isolated another VZV-MSP-like virus from an elderly man with herpes zoster. These gE mutant viruses may have arisen through independent mutation or may represent a distinct VZV subpopulation that emerged more than 50 years ago.