Complete genome sequence of a vampire bat-related rabies virus obtained by metagenomics from a patient with encephalitis of unknown etiology, French Guiana.

We report the complete genome sequence of a rabies virus obtained by direct metagenomics from the cerebellum of a gold panner who died of unknown encephalitis in French Guiana. Phylogenetic analysis exhibited a close genetic relationship with vampire bat-related isolates, confirming the second case of human rabies identified in this territory.

Molecular characterization of rabies virus from wild and domestic animals in the Sultanate of Oman.

AIMS: Rabies virus (RV) is endemic in some Arabian countries. However, it is difficult to control RV without understanding the epidemiological evolution of endemic RV isolates. The current study aimed to characterize RV from domestic and wild animal clinical cases in Oman. METHODS AND RESULTS: Twelve brain samples from domestic (Five camels, three goats and one cattle) and wild animals (Two foxes and one honey badger) were investigated from different locations in Oman between 2017 and 2020. All samples were confirmed by RV nucleoprotein (N) gene-specific primers. Seven out of the 12 amplified samples were successfully sequenced and subjected to sequence and phylogenetic analysis. The detected RVs shared an in-between 96.8%-98.7% and 96.9%-99% nucleotide and amino acid identities, respectively. However, the wild animal RVs shared only 92.6%-93.9% and 95.9% nucleotide and amino acid identities with the domestic animal RVs, respectively. Negri bodies were detected histologically in six brain samples from camels (n = 3), goats (n = 1) and foxes (n = 2). The RVs from domestic animals shared 97%-98.7% and 98%-100% nucleotide and amino acid identities with the previously published fox RVs from Oman and Gulf countries. Phylogenetic analysis suggested that all RV sequences belong to a distinct clade confined to the previously reported clade V within the Middle Eastern Cluster. CONCLUSIONS: As indicated by the analysis of RVs from different locations between 2017 and 2020, a genetic variant isolated to the Gulf region may exist within the Middle East clade. Moreover, it appears that new RV lineages are emerging rapidly within this region. Therefore, a comprehensive genomic and phylogenetic analysis of the circulating RV is important for the development of future prevention and control strategies.

Transcriptomic cell-type specificity of local cortical circuits.

Complex neocortical functions rely on networks of diverse excitatory and inhibitory neurons. While local connectivity rules between major neuronal subclasses have been established, the specificity of connections at the level of transcriptomic subtypes remains unclear. We introduce single transcriptome assisted rabies tracing (START), a method combining monosynaptic rabies tracing and single-nuclei RNA sequencing to identify transcriptomic cell types, providing inputs to defined neuron populations. We employ START to transcriptomically characterize inhibitory neurons providing monosynaptic input to 5 different layer-specific excitatory cortical neuron populations in mouse primary visual cortex (V1). At the subclass level, we observe results consistent with findings from prior studies that resolve neuronal subclasses using antibody staining, transgenic mouse lines, and morphological reconstruction. With improved neuronal subtype granularity achieved with START, we demonstrate transcriptomic subtype specificity of inhibitory inputs to various excitatory neuron subclasses. These results establish local connectivity rules at the resolution of transcriptomic inhibitory cell types.

Rabies in equids in Sudan.

Rabies is endemic in Sudan with continuing outbreaks occurring annually, the most common animals affected are dogs, followed by goats and equids. This work focused on equid rabies, to elucidate the current situation of the disease through analysis of reports of equid rabies outbreaks in Sudan during 2010-2022 supported by laboratory confirmation of the disease. During the study period, 66 animals were affected during 35 equid rabies outbreaks. The highest incidences were found in Al Gezira (30.3%), followed by Darfur (24.2%) and Kordofan (15.2%). The highest incidence rate was observed during 2018 (33.3%), followed by 2015 (16.7%). Within seasons, the highest incidence rate was reported during October - December (33.3%), followed by July - September (30.3%). Chi-square analysis revealed a significant correlation between rabid animals and year, season, and state. Wald statistics demonstrated that year and season had a significant association with the disease. Virus antigen was identified (72.2%) in brain tissues using the fluorescent antibody test. Viral nucleic acid was amplified (n = 6) with a reverse transcriptase polymerase chain reaction assay.Contribution: As equids are kept in close contact with humans and other animals in the country, according to the present investigation, equid rabies in Sudan is a potential public health concern, emphasising the importance of implementing effective control measures.

Immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals: A randomized, parallel-controlled of homologous vaccine with different immune procedure study.

This study was a randomized, parallel-controlled of homologous vaccines with different immune procedure research to evaluate the immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals. 240 subjects aged ≤ 20、21-50、≥51 y were randomly divided into 2 groups (1:1), Zagreb 2-1-1 regimen receivers as experimental group and Essen 5 regimen receivers as controlled group. Researchers collected venous blood of each subject before vaccine injection and on the day 7, 14, 42, 180, 365 after first dose. The immunogenicity and immune persistence was assessed by neutralizing antibody. The positive rate of neutralizing antibody in experimental group was 14.53% on the 7th day, and raised to 100% on the 14th day. It showed no significant difference between experimental and controlled group (P>0.05). Either in experimental or controlled group, GMC of neutralizing antibody was up to the peak on the 14th day, and it showed no significant difference between two groups (P>0.05). On the 42nd day, the antibody positive rate remained 100% with both Zagreb 2-1-1 and Essen 5 regimens, and the GMC of antibodies also remained high level. Then, on the 180th and 365th day with both regimens, the GMC of antibodies dropped dramatically, although it remained above the protective level of 0.5 IU/ml, the positive rates dropped to 84.40% and 84.11% (on the 180th day), and 61.29% and 58.62% (on the 365th day). Rabies vaccine injected by Zagreb 2-1-1 regimen can produce neutralizing antibody fastly and perdurably.Registration: ClinicalTrials.gov #NCT01821911and NCT01827917.

RABV antigenic peptide loaded polymeric nanoparticle production, characterization, and preliminary investigation of its biological activity.

Nanoparticle-based antigen carrier systems have become a significant area of research with the advancement of nanotechnology. Biodegradable polymers have emerged as particularly promising carrier vehicles due to their ability to address the limitations of existing vaccine systems. In this study, we successfully encapsulated the G5-24 linear peptide, located between amino acids 253 and 275 in the primary sequence of the rabies virus G protein, into biodegradable and biocompatible PLGA copolymer using the double emulsion solvent evaporation method. The resulting nanoparticles had a size of approximately 230.9 ± 0.9074 nm, with a PDI value of 0.168 ± 0.017 and a zeta potential value of -9.86 ± 0.132 mV. SEM images confirmed that the synthesized nanoparticles were uniform in size and distribution. Additionally, FTIR spectra indicated successful peptide loading into the nanoparticles. The encapsulation efficiency of the peptide-loaded nanoparticles was 73.3%, with a peptide loading capacity of 48.2% and a reaction yield of 30.4%. Peptide release studies demonstrated that 65.55% of the peptide was released in a controlled manner over 28 days, following a "biphasic burst release" profile consistent with the degradation profile of PLGA. This controlled release is particularly beneficial for vaccine studies. Cytotoxicity tests revealed that the R-NP formulation did not induce cytotoxicity in fibroblast cells and enhanced NO production in macrophages, indicating its potential for vaccine development.

Understanding the journey towards rabies vaccination for travellers: Results of a cross-sectional survey with patients and providers in the US, Germany, Sweden, and Switzerland.

BACKGROUND: Although cases of rabies in international travellers are uncommon, they are a fatal risk which can be alleviated through vaccination prior to travel. As international travel recovers post-COVID, it is vital that travellers are made aware of the risk of rabies when travelling to endemic countries and supported to receive the vaccine when eligible. METHODS: Online surveys were conducted in the US, Germany, Sweden and Switzerland between November 2022-January 2023 with both patients and healthcare providers (HCPs). Eligibility criteria for patients included those eligible for rabies pre-exposure prophylaxis (PrEP) due to travel location and activity; HCPs had to be providers of travel vaccinations. In both surveys, questions were asked about discussion of rabies vaccination, decision of whether to administer a rabies vaccine, recommendation to get the rabies vaccine, and final decision to get a vaccine. RESULTS: The final patient sample included n = 1557 patients who were eligible for rabies pre-exposure prophylaxis (US n = 504, Germany n = 353, Sweden n = 350, Switzerland n = 350) and n = 219 HCPs (US n = 75, Germany n = 75, Sweden n = 32, Switzerland n = 37). Although all patients in the sample were eligible for rabies vaccination, only 15 % felt they were at risk of getting rabies, and only 18 % received the rabies vaccine before their trip. HCPs reported discussing PrEP and/or PrEP and PEP with 30 % of patients presenting for travel vaccination advice, on average. CONCLUSIONS: Awareness and perception of rabies risk, and lack of consistent HCP discussion of the need for rabies PrEP may be major barriers to uptake of the vaccine for patients who are eligible to receive it.

Epidemiological Profile and Awareness Regarding Animal Bite Management in an Urban Area.

OBJECTIVES: The most common way for people to contract the deadly zoonotic disease rabies is through animal bites. This study was designed because there is a shortage of community-based data to determine the true extent of rabies infection and a lack of understanding regarding patient misconceptions in urban areas. The objective was to determine the scope of the issue and the epidemiological features of animal bite incidents. METHODOLOGY: This was a facility-based cross-sectional study conducted at the field practice area (Urban Health Training Centre) under the Department of Community Medicine, Government Medical College. The study duration was one year (May 2023 to April 2024). Consecutive patients (accompanied by an attendant) attending the Urban Health Training Centre were included in the study. A purposive sampling technique was used, and around 400 animal bite cases were recorded in one year at the Urban Health Training Centre. RESULTS: Out of 1503 male cases at the Urban Health Training Centre, around 255 were dog bite cases (50.6%), whereas out of 1302 females visiting the Urban Health Training Centre, around 145 were dog bite cases (48%). The majority (35%) belonged to the age group of 11 to 20 years for both males and females. The mean age of the cases was 19.4 ± 3.4 years. The study found a male preponderance (64%), with females constituting 36%. The right lower limb (49.5%), left lower limb (39%), and upper limb were the most frequently bitten sites. Fifty-one percent of the cases fell into Category II. According to local data, the most popular home management practices were ghee oil and cold treatments. Although Category III is the most severe bite, only 35% had taken the anti-rabies vaccine (ARV), and 8.75% had received rabies immunoglobulin. CONCLUSION: The public and medical community need to be made aware of the importance of wound care and the prudent use of the anti-rabies vaccine.

Contribution of artificial intelligence for understanding animal rabies epidemiology in Morocco: What are the perspectives of an innovative and predictive approaches?

Rabies is a major zoonotic disease legally notifiable in Morocco and elsewhere. Given the burden of rabies and its impact on public health, several national control programs have been implemented since 1986, without achieving their expected objectives. The aim of this study was to design a predictive analysis of rabies in Morocco. The expected outcome was the construction of probabilistic diagrams that can guide actions for the integrated control of this disease, involving all stakeholders, in the country. Such modeling is an essential step in operational epidemiology to optimize expenditure of public funds allocated to the integrated strategy for fighting this disease. The methodology employed combined the use of geospatial analysis tools (kriging) and artificial intelligence models (Machine Learning). In order to investigate the link between the risk of rabies within a territorial municipality (commune) and its socio-economic situation, the following data were analyzed: (1) health data: reported animal cases of rabies between 2004 and 2021 and data obtained through the ArcGIS kriging tool (Geospatial data); (2) demographic and socio-economic data. We compared several Machine Learning models. Of these, the "Imbalanced-Xgboost" model associated with kriging yielded the best results. After optimizing this model, we mapped our results for better visualization. The obtained results complement and consolidate previous study in this field with greater accuracy, showing a strong correlation between a commune's socio-economic status, its geographical location and its risk level of rabies. From this, 399 out of the 1546 communes have been identified as high-risk areas, accounting for 25.8% of the total number of communes. Under this risk-based approach, the results of these analyses make it practical to take targeted decisions for rabies prevention and control, as well as canine population control, in a territorial commune according to its risk level. Such an approach allows obvious optimized distribution of financial resources and adaptation of the control actions to be taken. The study highlights also the importance of using innovative technologies to refine epidemiological approaches and fill gaps in field data. Through this study, we hope to contribute to eradication of rabies in Morocco by providing reliable data and practical recommendations for control actions against rabies.

Analytical Methods for Evaluating the Immunogenicity of Recombinant Rabies Virus Glycoprotein Expressed in the Yeast Komagataella phaffii.

BACKGROUND: Rabies is a fatal viral disease preventable by vaccination. The multiple-dose regimens, along with the high production costs of current rabies vaccines, limit their use in rabies-endemic countries with developing economies and consequently there is a need for new efficacious, low-cost rabies vaccines. This study investigates the immunogenicity of recombinant rabies virus glycoprotein (rRABVG), expressed in the yeast Komagataella phaffii (K. phaffii), as a candidate subunit rabies vaccine. METHODS: Monoclonal antibodies were used to confirm neutralizing epitopes presence on the rRABVG. The rRABVG potency was estimated by antigen quantification methods using ELISA and SRID. Serological methods, specifically ELISA and RFFIT, were applied to investigate the immune response of mice groups immunized with rRABVG varying doses, with or without adjuvant. RESULTS: The potency estimated by antigen quantification was dependent on the method employed. Active immunization assessment using ELISA was effective when the solid-phase antigen is the rRABVG. The RFFIT data indicated that a single adjuvanted dose of 20 µg rRABVG is sufficient for virus-neutralizing antibodies induction at a protective level of 0.5 IU/mL within 10 days post immunization. CONCLUSION: These data demonstrate that K. phaffii produced rRABVG is immunoactive and could be an attractive candidate to develop a low-cost subunit rabies vaccine.

A single dose of recombinant adenoviral vector rabies vaccine expressing two copies of glycoprotein protects mice from lethal virus challenge.

INTRODUCTION: Rabies is a fatal infectious disease, that poses a major public health threat in developing countries. With an annual death toll of approximately 59,000, more than half of which are children, an urgent need exists for a safe, affordable, and effective preventive measure against rabies virus infection. METHODOLOGY: A recombinant rabies vaccine called Ad5-dRVG was constructed by introducing two copies of the rabies virus glycoprotein into a human adenoviral vector. Virus-neutralizing assays and virus challenge experiments were employed to evaluate the Ad5-dRVG vaccine. RESULTS: Our findings demonstrate that a single dose of Ad5-dRVG, administered either intramuscularly or orally, elicited significantly stronger immune responses than Ad5-RVG. Moreover, both vaccines provided complete protection in mice. Notably, the vaccine exhibited remarkable efficacy even at low doses, suggesting potential cost reduction in production. CONCLUSIONS: The development of the Ad5-dRVG recombinant rabies vaccine represents a significant advancement in rabies prevention. Its enhanced immunogenicity, demonstrated efficacy and potential cost savings make it a promising candidate for widespread use.

Rabies epidemiology in Malaysia (2015-2023): A cross-sectional insights and strategies for control.

BACKGROUND: Malaysia currently faces significant challenges in controlling the spread of dog-mediated human rabies, as evidenced by recurrent outbreaks in newly affected areas and increasing human fatalities. MATERIALS AND METHODS: A cross-sectional study was conducted to analyse surveillance data from 2015 to 2023 to examine the epidemiological characteristics of rabies in Malaysia. Data from multiple sources were used, and descriptive statistics, incidence rates, and reproductive numbers were calculated. QGIS software was used to map the distribution of rabies cases, and statistical methods were employed to evaluate associations between rabies incidence, vaccination coverage, and risk factors. We further explored the effectiveness of vaccination campaigns and public health interventions in reducing rabies transmission. RESULTS: Our findings revealed 995 confirmed rabies cases in animals. Sarawak reported the highest proportion of rabies cases at 97.99 %, showing a significant correlation between location and rabies cases (p < .001). Dogs comprised 89.35 % of confirmed cases, while the average annual vaccination rate was only 16.66 %, far below the 59.05 % needed for herd immunity. Moreover, human rabies cases reported in Sarawak had an alarmingly high fatality rate of 90.28 %, highlighting the urgent need for improved public health measures and surveillance. CONCLUSION: This research provides critical insights for policymakers and health officials to improve rabies control strategies in Malaysia.

Z-Ligustilide restricts rabies virus replication by inducing ferroptosis through the ACSL4-LPCAT3-POR pathway.

Rabies, induced by rabies virus (RABV), still threaten global health all over the world, and no effective therapy is available for rabies currently. Recently, a series of natural plant components have been found to inhibit virus production. In this study, Z-Ligustilide, a natural component of Ligusticum chuanxiong Hort, was found to inhibit RABV replication. Initially, the concentration of cytotoxicity 50 % (CC50) of Z-Ligustilide in N2a and BSR cells were 429.9 µM and 335.5 µM, respectively, which both significantly restrict RABV production in a concentration-dependent manner. Moreover, Z-Ligustilide was found to mainly inhibit the replication stage of RABV. Specifically, Z-Ligustilide can suppress lipid droplet (LD) formation via directly inhibiting diacylglycerol acyltransferase 1/2 (DGAT1/2) expression, which can further promote cellular lipid peroxidation, Fe2+ concentration, reactive oxygen species (ROS), and induce ferroptosis ultimately. Furthermore, Z-Ligustilide was demonstrated to increase ferroptosis via Acyl-CoA synthetase long-chain family member 4 (ACSL4)- Lysophosphatidylcholine Acyltransferase 3 (LPCAT3)- Cytochrome P450 Oxidoreductase (POR) pathway. Above all, this study explored the antiviral function of Z-Ligustilide, which provides a novel insight for developing anti-RABV drugs.

Rabies post-exposure prophylaxis: A retrospective analysis of timing of initiation and antibody responses in a Belgian cohort.

BACKGROUND: We aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center. METHODS: Retrospective analysis of patient records who attended our center from 2018 to 2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate. RESULTS: We reviewed 317 patient records. Among individuals with inland exposure (n = 103), 85 % timely received PEP. Among travelers exposed abroad (n = 214), administration of RIG and vaccine initiation were timely in 30 % and 50 % of cases, respectively. An adequate antibody response was detected in 99.5 % (195/196) individuals. CONCLUSION: Substantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients.

Factors associated with the rabies vaccination status of dogs in households in Beni City, D.R. Congo.

Human rabies transmitted by dogs still kills thousands of people each year worldwide. Dog bites are common in the city of Beni (Democratic Republic of Congo), which shows low rabies vaccination coverage. This study aimed to determine the factors associated with the rabies vaccination status of dogs. A cross-sectional analytical study was conducted in the town of Beni among dog owners, during a household survey selected using a multistage sampling. The information sought concerned the knowledge and characteristics of the dog owners as well as the vaccination status of these dogs. Logistic regression was used to investigate associations between the vaccination status of the dogs and the main independent factors. Rabies vaccination coverage in Beni was 26% (95% confidence interval [CI]: 22% - 30%). The main factors associated with the rabies vaccination status of the dog were primary education level of household head (adjusted odds ratio [aOR]:4.8; 95% CI: 1.2- 19.8); university education level of household head (aOR: 5.9; 95% CI: 1.6-22); perceived rabies severity (aOR: 44. 4; 95% CI: 10.4-188), having more than one dog in the household (aOR: 2.6; 95% CI: 1.6-4.3); age range 7-12 months (aOR: 0.2; 95% CI: 0.1-0.6) and confined dog breeding (aOR: 3.9; 95% CI: 1.1-14.9). The low vaccination coverage in Beni requires mass vaccination campaigns against canine rabies targeting the dog owners with low education levels, those raising more than one dog, with stray dogs or dogs less than 12 months old.

Study of dog population dynamics and rabies awareness in Thailand using a school-based participatory research approach.

Rabies is a neglected disease primarily related to dog-mediated transmission to humans. Accurate dog demographic and dynamic data are essential for effectively planning and evaluating population management strategies when designing interventions to prevent rabies. However, in Thailand, longitudinal survey data regarding dog population size are scarce. A school-based participatory research (SBPR) approach was conducted to survey owned dogs for one year in four high-risk provinces (Chiang Rai, Surin, Chonburi, and Songkhla) of Thailand, aiming to understand dog population dynamics and raise awareness about rabies. 'Pupify' mobile application was developed to collect data on dog population and observe the long-term population dynamics in this study. At the end of the data collection period, telephone interviews were conducted to gain insight into contextual perceptions and awareness regarding both animal and human rabies, as well as the social responsibility of dog owners in disease prevention and control. Among 303 high school students who registered in our study, 218 students reported at least one update of their dog information throughout the one-year period. Of 322 owned dogs from our survey, the updates of dog status over one year showed approximately 7.5 newborns per 100-dog-year, while deaths and missing dogs were 6.2 and 2.7 per 100-dog-year, respectively. The male to female ratio was approximately 1.8:1. Twenty-three students (10%) voluntarily participated and were interviewed in the qualitative study. The levels of rabies awareness and precautions among high-school students were relatively low. The high dropout rate of the survey was due to discontinuity in communication between the researcher and the students over the year. In conclusion, this study focused on using the SBPR approach via mobile application to collect data informing dog population dynamics and raising awareness regarding rabies in Thailand Other engaging platforms (e.g. Facebook, Instagram, Twitter, and other popular applications) is necessary to enhance communication and engagement, thereby sustaining and maintaining data collection. Further health education on rabies vaccination and animal-care practices via social media platforms would be highly beneficial. For sustainable disease control, engaging communities to raise awareness of rabies and increase dog owners' understanding of their responsibilities should be encouraged.

Rise in rabies cases in Jammu region: A problem that requires urgent attention.

Context: Rabies is a fatal zoonotic disease that is endemic in India. Both forms of rabies, namely, encephalitic and furious, invariably lead to coma and death. Lack of awareness is the most critical barrier in accessing timely post-exposure prophylaxis that can prevent the progression to clinical disease. Aims: To report the case series of fourteen clinically suspected rabies cases. Settings and Design: We followed a retrospective study design. Data were collected from the Anti Rabies Section of Government Medical College, Jammu, which is a tertiary care hospital of Jammu Division. Methods and Material: We collected data of all patients over a period of three years, from 2017 to 2020, who were diagnosed as cases of clinically suspected rabies on the basis of classic signs and symptoms and who finally succumbed to the disease. Statistical Analysis Used: Descriptive statistics was used to describe the results of the study. Results: In the present description, the mean age of the patients was 31 ± 18.6 years. Out of 14 suspected cases, 9 had not received any post-exposure prophylaxis-neither vaccine nor serum-and instead visited spiritual faith healers. The remaining patients had history of either incomplete, unknown, or incorrect vaccination status. Median duration of presentation of symptoms after dog bite was 42 days, with a range of 15-180 days. Mean survival of patients after presentation of symptoms was around 1.8 days. Conclusions: Low level of awareness resulted in non-seeking of health-care services after animal bites.

Epidemiological characteristics of human rabies cases reported by sites in China from 2006 to 2022.

BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.

Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-κB Signaling Pathways via TLR7.

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.