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PLoS Neglected Tropical Diseases Jul 2023Rabies is the oldest fatal zoonotic disease recognised as a neglected tropical disease and is caused by an RNA virus belonging to the genus Lyssavirus, family...
BACKGROUND
Rabies is the oldest fatal zoonotic disease recognised as a neglected tropical disease and is caused by an RNA virus belonging to the genus Lyssavirus, family Rhabdoviridae.
METHODOLOGY/PRINCIPAL FINDINGS
A deep molecular analysis was conducted on full-length nucleoprotein (N) gene and whole genome sequences of rabies virus from 37 animal brain samples collected between 2012 and 2017 to study the circulation of rabies virus (RABV) variants. The overall aim was to better understand their distribution in Moldova and north-eastern Romania. Both Sanger and high throughput sequencing on Ion Torrent and Illumina platforms were performed. Phylogenetic analysis of the RABV sequences from both Moldova and Romania revealed that all the samples (irrespective of the year of isolation and the species) belonged to a single phylogenetic group: north-eastern Europe (NEE), clustering into three assigned lineages: RO#5, RO#6 and RO#7.
CONCLUSIONS/SIGNIFICANCE
High throughput sequencing of RABV samples from domestic and wild animals was performed for the first time for both countries, providing new insights into virus evolution and epidemiology in this less studied region, expanding our understanding of the disease.
Topics: Animals; Rabies virus; Phylogeny; Romania; Moldova; Rabies; Whole Genome Sequencing
PubMed: 37410714
DOI: 10.1371/journal.pntd.0011446 -
Veterinary World Dec 2023Rabies has been endemic in Bali since 2009, and cases has recently increased. Unfortunately, there is a lack of available vaccines, which hinders the eradication...
BACKGROUND AND AIM
Rabies has been endemic in Bali since 2009, and cases has recently increased. Unfortunately, there is a lack of available vaccines, which hinders the eradication program. This study aimed to investigate the epidemiological and virological aspects of rabies infection in Bali.
MATERIALS AND METHODS
A total of 24 brain samples were collected from rabid dogs in all districts of Bali. The samples were tested using the direct fluorescent antibody (DFA) test and polymerase chain reaction (PCR) to confirm the presence of rabies virus in the samples. Samples with the highest virus content were propagated and then inoculated into BALB/c mice. The brains of dead mice were used to prepare an inoculate cultured in murine neuroblastoma cells. Supernatant-positive viruses representing each district were then reinoculated into eight groups of five BALB/c mice. A brain sample from each dead mouse was tested using DFA and PCR and detected under a fluorescence microscope.
RESULTS
All rabies virus-positive samples collected from rabid dogs in all districts of Bali were positive. Rabies virus was detected by DFA test and PCR and was consistently confirmed in the and studies. BALB/c mice inoculated with the highest viral dilution (105 cells/mL) of culture supernatant showed typical signs of rabies, indicating that the virus could be properly investigated.
CONCLUSION
This study demonstrated a wide epidemiological distribution of rabies in Bali. The obtained virus can be adapted for and studies and can be used to develop a homologous vaccine.
PubMed: 38328353
DOI: 10.14202/vetworld.2023.2446-2450 -
Zhonghua Yi Xue Za Zhi Aug 2023Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%....
Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.
Topics: Humans; Rabies; Rabies virus; Rabies Vaccines; Immunosuppressive Agents; Antibodies, Monoclonal; Antibodies, Viral
PubMed: 37491162
DOI: 10.3760/cma.j.cn112137-20230307-00341 -
BioRxiv : the Preprint Server For... Aug 2023A diverse group of RNA viruses including Rabies, Polio, La Crosse, West Nile, Zika, Nipah, Eastern and Western equine encephalitis, Venezuelan equine encephalitis,...
A diverse group of RNA viruses including Rabies, Polio, La Crosse, West Nile, Zika, Nipah, Eastern and Western equine encephalitis, Venezuelan equine encephalitis, Japanese encephalitis, and tick-borne encephalitis viruses have the ability to gain access to and replicate in the central nervous system (CNS), causing severe neurological disease. Current treatment for these patients is generally limited to supportive care. To address the need for a generalizable antiviral, we utilized a strategy of mutagenesis to limit virus replication. We evaluated ribavirin (RBV), favipiravir (FAV) and -hydroxycytidine (NHC) against La Crosse virus (LACV) which is the primary cause of pediatric arboviral encephalitis cases in North America. NHC was more potent than RBV or FAV in neuronal cells. Oral administration of molnupiravir (MOV), the 5'-isobutyryl prodrug of NHC, decreased neurological disease development by 32% following intraperitoneal (IP) infection of LACV. MOV also reduced disease by 23% when virus was administered intranasally (IN). NHC and MOV produced less fit viruses by incorporating predominantly G-to-A or C-to-U mutations. Furthermore, NHC also inhibited two other orthobunyaviruses, Jamestown Canyon virus and Cache Valley virus. Collectively, these studies indicate that NHC/MOV has therapeutic potential to inhibit virus replication and subsequent neurological disease caused by this neurotropic RNA virus.
PubMed: 37662274
DOI: 10.1101/2023.08.22.554316 -
Vector Borne and Zoonotic Diseases... Sep 2023Australian bat lyssavirus (ABLV) is a negative-sense, single-stranded RNA rhabdovirus capable of causing fatal acute encephalitis in humans with similar pathogenesis to... (Review)
Review
Australian bat lyssavirus (ABLV) is a negative-sense, single-stranded RNA rhabdovirus capable of causing fatal acute encephalitis in humans with similar pathogenesis to its closest serologic relative, rabies virus (RABV). In this review, we describe emergence and classification of ABLV, its known virology, reservoirs, and hosts, as well as both the pathogenesis and treatment approaches currently employed for presumed infections. ABLV was first identified in New South Wales, Australia in 1996 and emerged in humans months later in Queensland, Australia. Only five known bat reservoirs, all of which fall within the and genera, have been identified to date. Although ABLV antigens have been identified in bats located outside of Australia, the three known human ABLV infections to date have occurred within Australia. As such, there remains a potential for ABLV to expand its presence within and beyond Australia. ABLV infections are currently treated as if they were RABV infections by administering neutralizing antibodies against RABV at the site of the wound and employing the rabies vaccine upon possible exposures. Due to its recent emergence, there is still much left unknown about ABLV, posing concerns with how to safely and effectively address current and future ABLV infections.
Topics: Humans; Animals; Australia; Rhabdoviridae Infections; Lyssavirus; Rabies virus; Tropism; Chiroptera
PubMed: 37335942
DOI: 10.1089/vbz.2022.0089 -
BioRxiv : the Preprint Server For... Mar 2024Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression . Synaptic...
Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.
PubMed: 38496540
DOI: 10.1101/2024.03.01.583047 -
Emerging Microbes & Infections Dec 2023The persistence and clinical consequences of rabies virus (RABV) infection have prompted global efforts to develop a safe and effective vaccines against rabies. mRNA...
The persistence and clinical consequences of rabies virus (RABV) infection have prompted global efforts to develop a safe and effective vaccines against rabies. mRNA vaccines represent a promising option against emerging and re-emerging infectious diseases, gaining particular interest since the outbreak of COVID-19. Herein, we report the development of a highly efficacious rabies mRNA vaccine composed of sequence-modified mRNA encoding RABV glycoprotein (RABV-G) packaged in core-shell structured lipopolyplex (LPP) nanoparticles, named LPP-mRNA-G. The bilayer structure of LPP improves protection and delivery of RABV-G mRNA and allows gradual release of mRNA molecules as the polymer degrades. The unique core-shell structured nanoparticle of LPP-mRNA-G facilitates vaccine uptake and demonstrates a desirable biodistribution pattern with low liver targeting upon intramuscular immunization. Single administration of low-dose LPP-mRNA-G in mice elicited potent humoral immune response and provided complete protection against intracerebral challenge with lethal RABV. Similarly, single immunization of low-dose LPP-mRNA-G induced high levels of virus-neutralizing antibody titers in dogs. Collectively, our data demonstrate the potential of LPP-mRNA-G as a promising next-generation rabies vaccine used in human and companion animals.
Topics: Dogs; Animals; Mice; Humans; Rabies; Rabies Vaccines; Immunity, Humoral; Tissue Distribution; Antibodies, Viral; mRNA Vaccines; Rabies virus; Immunization; RNA, Messenger
PubMed: 37819147
DOI: 10.1080/22221751.2023.2270081 -
One Health (Amsterdam, Netherlands) Dec 2023Rabies is an acute zoonotic infectious disease caused by rabies virus. In 2015, the World Health Organization proposed the goal of eliminating dog-induced human rabies...
Rabies is an acute zoonotic infectious disease caused by rabies virus. In 2015, the World Health Organization proposed the goal of eliminating dog-induced human rabies by 2030. In response to this goal positively, China has been dedicated to the control and elimination of rabies mainly caused by dogs, for nearly 10 years. By applying infectious disease dynamics, in this paper, we establish a dog-human rabies transmission model to forecast future epidemic trends of rabies, assess whether the goal of eliminating dog-induced human rabies cases in China can be achieved in 2030, and further evaluate and suggest the follow-up sustained preventive measures after the elimination of human rabies. By analyzing and simulating above dynamic model, it is concluded that rabies has been well controlled in China in recent years, but dog-induced human rabies cannot be eliminated by 2030 according to current situation. In addition, we propose to improve rabies control efforts by increasing the immunization coverage rate of rural domestic dogs, controlling the number of stray dogs and preventing the import of rabies virus in wild animals. Immunization coverage rate of rural domestic dogs which is currently less than 10% is far from requirement, and it needs to reach 50%-60% to meet the goal of 2030. Since it is difficult to immunize stray dogs, we suggest to control the number of stray dogs below 15.27 million to achieve the goal. If the goal of eliminating human rabies is reached in 2030, the essential immunization coverage needs to be maintained for 18 years to reduce the number of canine rabies cases to zero. Lastly, to prevent transmission of rabies virus from wild animals to dogs, the thresholds of the number of dogs and the immunization coverage rate of dogs after eliminating canine rabies cases are also discussed.
PubMed: 37638210
DOI: 10.1016/j.onehlt.2023.100615 -
Veterinary Microbiology Sep 2023Rabies, which caused by rabies virus (RABV), is a zoonotic and life-threatening disease with 100% mortality, and there is no effective treatment thus far due to the...
Rabies, which caused by rabies virus (RABV), is a zoonotic and life-threatening disease with 100% mortality, and there is no effective treatment thus far due to the unclear pathogenesis and less of treatment targets. Interferon-induced transmembrane protein 3 (IFITM3) has recently been identified as an important anti-viral host effector induced by type I interferon. However, the role of IFITM3 in RABV infection has not been elucidated. In this study, we demonstrated that IFITM3 is a crucial restriction factor for RABV, the viral-induced IFITM3 significantly inhibited RABV replication, while knockdown of IFITM3 had the opposite effect. We then identified that IFNβ induces the upregulation of IFITM3 in the absence or presence of RABV infection, meanwhile, IFITM3 positively regulates RABV-triggered production of IFNβ in a feedback manner. In-depth research we found that IFITM3 not only inhibits the virus absorb and entry, but also inhibits viral replication through mTORC1-dependent autophagy. All these findings broaden our understanding of IFITM3 function and uncover a novel mechanism against RABV infection.
Topics: Animals; Rabies virus; Rabies; Virus Internalization; Virus Replication; Interferon Type I; Autophagy
PubMed: 37392666
DOI: 10.1016/j.vetmic.2023.109823 -
Future Microbiology Apr 2024The emergence of highly zoonotic viral infections has propelled bat research forward. The viral outbreaks including Hendra virus, Nipah virus, Marburg virus, Ebola... (Review)
Review
The emergence of highly zoonotic viral infections has propelled bat research forward. The viral outbreaks including Hendra virus, Nipah virus, Marburg virus, Ebola virus, Rabies virus, Middle East respiratory syndrome coronavirus, SARS-CoV and the latest SARS-CoV-2 have been epidemiologically linked to various bat species. Bats possess unique immunological characteristics that allow them to serve as a potential viral reservoir. Bats are also known to protect themselves against viruses and maintain their immunity. Therefore, there is a need for in-depth understanding into bat-virus biology to unravel the major factors contributing to the coexistence and spread of viruses.
PubMed: 38648093
DOI: 10.2217/fmb-2023-0233