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Academic Emergency Medicine : Official... Nov 2023Approximately 55,000 patients per year in the United States are exposed to potentially rabid animals and receive rabies postexposure prophylaxis (PEP) and these patients... (Review)
Review
Approximately 55,000 patients per year in the United States are exposed to potentially rabid animals and receive rabies postexposure prophylaxis (PEP) and these patients commonly present to the emergency department (ED) for wound care and PEP. Despite the number of rabies exposures seen in EDs each year, there appears to be a knowledge gap among health care providers with regard to prescribing and administering rabies PEP. The following review aims to bridge that knowledge gap by discussing the importance of obtaining a comprehensive exposure history to determine the category of the encounter, the type of animal, and the location of the bite and of consulting outside expert resources to determine whether the rabies PEP series is indicated. In addition, this article will discuss dosing, administration, and schedule of the rabies vaccine and human rabies immune globulin to ensure patients are fully protected from developing rabies. Lastly, this article discusses the potential cost associated with rabies PEP and provides information on managing this barrier.
Topics: Animals; Humans; United States; Rabies; Rabies Vaccines; Immunoglobulins; Post-Exposure Prophylaxis; Emergency Medicine; Bites and Stings
PubMed: 37245074
DOI: 10.1111/acem.14755 -
The Veterinary Clinics of North... May 2024Ferrets are bred to be pets, utilized for hunting, and as laboratory models. Despite the fact that ferrets in some areas of the world are neutered by the breeder before... (Review)
Review
Ferrets are bred to be pets, utilized for hunting, and as laboratory models. Despite the fact that ferrets in some areas of the world are neutered by the breeder before entering the pet trade, the importance of pediatric management should not be overlooked. Pregnant, whelping, and lactating jills should be closely monitored and kept in a quiet, stress-free environment. Hand-rearing baby kits is very challenging due to their requirement for ferret milk. Minimizing maternal stress and disease can prevent the need to hand rear kits. Infectious diseases in juvenile ferrets include canine distemper virus, rotavirus, coccidiosis, feline panleukopenia virus (experimental only), and Toxoplasma-like disease. All juvenile ferrets should be vaccinated against canine distemper and rabies. Congenital diseases are reported to affect the auditory, ocular, cardiovascular, urogenital, central nervous, and musculoskeletal systems. Early detection of these diseases is important to prevent the progression of curable diseases.
Topics: Humans; Dogs; Female; Animals; Ferrets; Lactation; Rabies; Distemper Virus, Canine; Distemper; Dog Diseases
PubMed: 38040563
DOI: 10.1016/j.cvex.2023.11.002 -
Nature Oct 2023Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory...
Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory infections, haemorrhagic fever and encephalitis in humans and animals, and are considered a substantial health and economic burden worldwide. Replication and transcription of the viral genome are executed by the large (L) polymerase, which is a promising target for the development of antiviral drugs. Here, using the L polymerase of EBOV as a representative, we show that de novo replication of L polymerase is controlled by the specific 3' leader sequence of the EBOV genome in an enzymatic assay, and that formation of at least three base pairs can effectively drive the elongation process of RNA synthesis independent of the specific RNA sequence. We present the high-resolution structures of the EBOV L-VP35-RNA complex and show that the 3' leader RNA binds in the template entry channel with a distinctive stable bend conformation. Using mutagenesis assays, we confirm that the bend conformation of the RNA is required for the de novo replication activity and reveal the key residues of the L protein that stabilize the RNA conformation. These findings provide a new mechanistic understanding of RNA synthesis for polymerases of non-segmented negative-strand RNA viruses, and reveal important targets for the development of antiviral drugs.
Topics: Animals; Humans; Antiviral Agents; Ebolavirus; Hemorrhagic Fever, Ebola; RNA, Viral; RNA-Dependent RNA Polymerase; Virus Replication; Genome, Viral; Nucleic Acid Conformation; Mutagenesis; RNA Stability
PubMed: 37699521
DOI: 10.1038/s41586-023-06608-1 -
Cells Jan 2024Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded... (Review)
Review
Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded animals, including humans. Autophagy and apoptosis are two evolutionarily conserved and genetically regulated processes that maintain cellular and organismal homeostasis, respectively. Autophagy recycles unnecessary or dysfunctional intracellular organelles and molecules in a cell, whereas apoptosis eliminates damaged or unwanted cells in an organism. Studies have shown that RABV can induce both autophagy and apoptosis in target cells. To advance our understanding of pathogenesis of rabies, this paper reviews the molecular mechanisms of autophagy and apoptosis induced by RABV and the effects of the two cellular events on RABV replication.
Topics: Animals; Humans; Rabies virus; Rabies; Apoptosis; Autophagy; Virus Replication
PubMed: 38247875
DOI: 10.3390/cells13020183 -
Methods in Molecular Biology (Clifton,... 2024Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral... (Review)
Review
Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral as well as the cellular immune system.This chapter focuses on RNA vaccines derived from negative-strand RNA viruses from the order Mononegavirales with special attention to Newcastle disease virus-based vaccines and their generation. It shall provide an overview on the advantages and disadvantages of certain vector platforms as well as their scopes of application, including an additional section on experimental COVID-19 vaccines.
Topics: Animals; Humans; COVID-19; Genetic Vectors; Newcastle disease virus; RNA Viruses; SARS-CoV-2; Viral Vaccines; mRNA Vaccines
PubMed: 38814390
DOI: 10.1007/978-1-0716-3770-8_3 -
Viruses Jan 2024Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has... (Review)
Review
Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies.
Topics: Humans; Animals; Dogs; Rabies; Zoonoses; Rabies virus; Encephalitis; Rabies Vaccines
PubMed: 38275970
DOI: 10.3390/v16010160 -
Redox Biology Aug 2023Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has...
Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.
Topics: Animals; Mice; Cholesterol; COVID-19; Homeostasis; SARS-CoV-2; Virus Internalization; Cholesterol 24-Hydroxylase
PubMed: 37285742
DOI: 10.1016/j.redox.2023.102769 -
International Journal of Medical... 2023Rabies continues to be a huge threat to public health. The rabies virus envelope glycoprotein (RABV G) is a major rabies virus antigen and contains neutralizing...
Rabies continues to be a huge threat to public health. The rabies virus envelope glycoprotein (RABV G) is a major rabies virus antigen and contains neutralizing epitopes, which are primary candidates for subunit vaccines and diagnostic antigens. However, the production and purification of rRABV G while retaining its antigenic and immunogenic remains to be a challenge. Here, we aimed to establish a platform for rRABV G production and purification, and determine the immunogenicity and antigenicity of rRABV G. The cDNA fragment encoding the soluble form of RABV G was synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-RABV G-eGFP was packaged, titered, and then transduced into HEK 293T cells. The cell culture supernatant was purified using nickel affinity chromatography and subsequently confirmed through Western Blot analysis and indirect enzyme-linked immunosorbent assay (ELISA). The ELISA utilized human sera obtained from individuals who had been vaccinated with the human commercial Purified Vero Cells Rabies Vaccine (PVRV). Notably, we observed a neutralizing antibody response in immunized pigs rather than in mice. This discrepancy could potentially be attributed to factors such as the instability of the rRABV G protein, variations in host responses, and variances in the adjuvant used. Taking all these findings into account, the rRABV G protein generated in this study exhibits promise as a potential vaccine candidate for the prevention of rabies.
Topics: Chlorocebus aethiops; Humans; Animals; Mice; Swine; Rabies virus; Rabies; HEK293 Cells; Vero Cells; Antibodies, Viral; Glycoproteins; Rabies Vaccines; Viral Envelope Proteins; Recombinant Proteins
PubMed: 37786447
DOI: 10.7150/ijms.87134 -
Viruses Jul 2023This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics... (Review)
Review
This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, , . The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.
Topics: Humans; Immunoglobulins; Globulins; Immunization, Passive; Vaccines; Communicable Diseases; Antibodies, Viral
PubMed: 37515229
DOI: 10.3390/v15071543 -
CNS Neuroscience & Therapeutics Dec 2023The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive...
OBJECTIVE
The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole-brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons.
METHODS
This study used retrograde tracing systems based on the rabies virus, Cre-LoxP technology, and immunofluorescence analysis.
RESULTS
We found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors.
CONCLUSION
The LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.
Topics: Mice; Animals; Periaqueductal Gray; Brain; Neurons; Hypothalamus; Preoptic Area
PubMed: 37424163
DOI: 10.1111/cns.14338