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Frontiers in Microbiology 2023TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral...
TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.
PubMed: 38107853
DOI: 10.3389/fmicb.2023.1284439 -
Open Veterinary Journal Nov 2023An infectious disease known as rabies (family Rhabdoviridae, genus ) causes severe damage to mammals' central nervous systems (CNS). This illness has been around for a... (Review)
Review
An infectious disease known as rabies (family Rhabdoviridae, genus ) causes severe damage to mammals' central nervous systems (CNS). This illness has been around for a very long time. The majority of human cases of rabies take place in underdeveloped regions of Africa and Asia. Following viral transmission, the Rhabdovirus enters the peripheral nervous system and proceeds to the CNS, where it targets the encephalon and produces encephalomyelitis. Postbite prophylaxis requires laboratory confirmation of rabies in both people and animals. All warm-blooded animals can transmit the infection, while the virus can also develop in the cells of cold-blooded animals. In the 21st century, more than 3 billion people are in danger of contracting the rabies virus in more than 100 different nations, resulting in an annual death toll of 50,000-59,000. There are three important elements in handling rabies disease in post exposure prophylaxis (PEP), namely wound care, administration of anti-rabies serum, and anti-rabies vaccine. Social costs include death, lost productivity as a result of early death, illness as a result of vaccination side effects, and the psychological toll that exposure to these deadly diseases has on people. Humans are most frequently exposed to canine rabies, especially youngsters and the poor, and there are few resources available to treat or prevent exposure, making prevention of human rabies challenging.
Topics: Animals; Humans; Dogs; Rabies; Rabies Vaccines; Rabies virus; Animals, Domestic; Vaccination; Mammals; Dog Diseases
PubMed: 38107233
DOI: 10.5455/OVJ.2023.v13.i11.1 -
Frontiers in Public Health 2023The fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals...
INTRODUCTION
The fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from bats that were captured for human consumption in Makurdi, Nigeria.
METHODS
Using pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the and families.
RESULTS
We report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; < 0.001), Nipah virus (odds ratio 4.04; = 0.00031), bat influenza H17N10 virus (odds ratio 7.25; < 0.001) and no significant association with Ebola virus (odds ratio 0.56; = 0.375) in this bat cohort.
CONCLUSION
The data suggest a potential risk of zoonotic spillover including the possible circulation of highly pathogenic viruses in populations. These findings highlight the importance of maintaining sero-surveillance of and the necessity for further, more comprehensive investigations to monitor changes in virus prevalence, distribution over time, and across different geographic locations.
Topics: Animals; Humans; Nigeria; Chiroptera; Zoonoses; Antibodies, Neutralizing; Virus Diseases
PubMed: 38106901
DOI: 10.3389/fpubh.2023.1283113 -
Vaccine Apr 2024A new generation, serum-free, antibiotic-free, purified Vero rabies vaccine (PVRV-NG; Sanofi) has been developed based on the same Pitman-Moore viral strain used for the...
Safety and immunogenicity of a serum-free purified Vero rabies vaccine in comparison with the rabies human diploid cell vaccine (HDCV; Imovax® Rabies) administered in a simulated rabies post-exposure regimen in healthy adults.
A new generation, serum-free, antibiotic-free, purified Vero rabies vaccine (PVRV-NG; Sanofi) has been developed based on the same Pitman-Moore viral strain used for the currently licensed purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi) and human diploid cell vaccine (HDCV; Imovax® Rabies, Sanofi). PVRV-NG has demonstrated a satisfactory safety profile and induces robust immune responses, with non-inferiority demonstrated versus PVRV when given as a three-dose pre-exposure prophylaxis (PrEP) regimen in healthy children and adults. Here, we evaluated the safety and immunogenic non-inferiority of PVRV-NG compared to HDCV when administered as simulated post-exposure prophylaxis (PEP), with concomitant administration of human rabies immunoglobulin (HRIG), in healthy adults in the USA. Participants were vaccinated according to the 5-dose Essen intramuscular regimen (4-week, 1-injection site regimen, with a single dose given on days 0, 3, 7, 14 and 28) for PEP, with concomitant HRIG administered on day 0. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 14, 28 and 42. Non-inferiority of PVRV-NG compared with HDCV was shown if the lower limit of the 95 % confidence interval (CI) for the difference in seroconversion rates (RVNA titers ≥ 0.5 IU/mL on day 14) between PVRV-NG and HDCV was above the non-inferiority margin of -5 %. Safety was evaluated after each vaccination and monitored throughout the study. The difference in seroconversion rate between the PVRV-NG and HDCV groups was -2.8 % (95 % CI, -8.08 to 4.20), indicating that non-inferiority was not demonstrated. The seroconversion rate was < 99 % in both study groups on day 14. There were no major safety concerns identified, and PVRV-NG demonstrated a similar safety profile to HDCV.
Topics: Adult; Child; Animals; Chlorocebus aethiops; Humans; Rabies; Rabies Vaccines; Antibodies, Viral; Rabies virus; Vaccination; Vero Cells; HIV Seropositivity
PubMed: 38105138
DOI: 10.1016/j.vaccine.2023.11.052 -
ELife Dec 2023Retrograde monosynaptic tracing using glycoprotein-deleted rabies virus is an important component of the toolkit for investigation of neural circuit structure and...
Retrograde monosynaptic tracing using glycoprotein-deleted rabies virus is an important component of the toolkit for investigation of neural circuit structure and connectivity. It allows for the identification of first-order presynaptic connections to cell populations of interest across both the central and peripheral nervous system, helping to decipher the complex connectivity patterns of neural networks that give rise to brain function. Despite its utility, the factors that influence the probability of transsynaptic rabies spread are not well understood. While it is well established that expression levels of rabies glycoprotein used to trans-complement G-deleted rabies can result in large changes in numbers of inputs labeled per starter cell (convergence index [CI]), it is not known how typical values of CI relate to the proportions of synaptic contacts or input neurons labeled. And it is not known whether inputs to different cell types, or synaptic contacts that are more proximal or distal to the cell body, are labeled with different probabilities. Here, we use a new rabies virus construct that allows for the simultaneous labeling of pre- and postsynaptic specializations to quantify the proportion of synaptic contacts labeled in mouse primary visual cortex. We demonstrate that with typical conditions about 40% of first-order presynaptic excitatory synapses to cortical excitatory and inhibitory neurons are labeled. We show that using matched tracing conditions there are similar proportions of labeled contacts onto L4 excitatory pyramidal, somatostatin (Sst) inhibitory, and vasoactive intestinal peptide (Vip) starter cell types. Furthermore, we find no difference in the proportions of labeled excitatory contacts onto postsynaptic sites at different subcellular locations.
Topics: Mice; Animals; Rabies virus; Rabies; Neurons; Synapses; Glycoproteins
PubMed: 38096019
DOI: 10.7554/eLife.89297 -
The Journal of Veterinary Medical... Jan 2024Rabies is a fatal zoonotic, neurological disease caused by rabies lyssavirus (RABV) and other lyssaviruses. In this study, we established novel serological neutralizing...
Rabies is a fatal zoonotic, neurological disease caused by rabies lyssavirus (RABV) and other lyssaviruses. In this study, we established novel serological neutralizing tests (NT) based on vesicular stomatitis virus pseudotypes possessing all 18 known lyssavirus glycoproteins. Applying this system to comparative NT against rabbit sera immunized with current RABV vaccines, we showed that the current RABV vaccines fail to elicit sufficient neutralizing antibodies against lyssaviruses other than to those in phylogroup I. Furthermore, comparative NT against rabbit antisera for 18 lyssavirus glycoproteins showed glycoproteins of some lyssaviruses elicited neutralizing antibodies against a broad range of lyssaviruses. This novel testing system will be useful to comprehensively detect antibodies against lyssaviruses and evaluate their cross-reactivities for developing a future broad-protective vaccine.
Topics: Animals; Rabbits; Lyssavirus; Rabies; Antibodies, Viral; Viral Pseudotyping; Rabies virus; Antibodies, Neutralizing; Rabies Vaccines; Glycoproteins; Zoonoses
PubMed: 38092389
DOI: 10.1292/jvms.23-0463 -
EFSA Journal. European Food Safety... Dec 2023This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and...
This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and surveillance activities carried out in 2022 in 27 Member States (MSs), the United Kingdom (Northern Ireland) and 11 non-MSs. Key statistics on zoonoses and zoonotic agents in humans, food, animals and feed are provided and interpreted historically. In 2022, the first and second most reported zoonoses in humans were campylobacteriosis and salmonellosis, respectively. The number of cases of campylobacteriosis and salmonellosis remained stable in comparison with 2021. Nineteen MSs and the United Kingdom (Northern Ireland) achieved all the established targets in poultry populations for the reduction of prevalence for the relevant serovars. samples from carcases of various animal species, and samples for quantification from broiler carcases, were more frequently positive when performed by the competent authorities than when own checks were conducted. Yersiniosis was the third most reported zoonosis in humans, followed by Shiga toxin-producing (STEC) and infections. and West Nile virus infections were the most severe zoonotic diseases, with the most hospitalisations and highest case fatality rates. In 2022, reporting showed an increase of more than 600% compared with 2021 in locally acquired cases of human West Nile virus infection, which is a mosquito-borne disease. In the EU, the number of reported foodborne outbreaks and cases, hospitalisations and deaths was higher in 2022 than in 2021. The number of deaths from outbreaks was the highest ever reported in the EU in the last 10 years, mainly caused by and to a lesser degree by . and in particular Enteritidis remained the most frequently reported causative agent for foodborne outbreaks. Norovirus (and other calicivirus) was the agent associated with the highest number of outbreak human cases. This report also provides updates on brucellosis, (Q fever), echinococcosis, rabies, toxoplasmosis, trichinellosis, infection with complex (focusing on and ) and tularaemia.
PubMed: 38089471
DOI: 10.2903/j.efsa.2023.8442 -
MBio Jan 2024messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the...
messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the nonspecificity of lipid nanoparticle-encapsulated (LNP) delivery systems result in the need for cold storage and a relatively short-duration immune response to mRNA vaccines. Herein, we develop a novel vaccine in the form of circRNAs encapsulated in LNPs, and the circular structure of the circRNAs enhances their stability. Lyophilization is considered the most effective method for the long-term preservation of RNA vaccines. However, this process may result in irreversible damage to the nanoparticles, particularly the potential disruption of targeting modifications on LNPs. During the selection of lymph node-targeting ligands, we found that LNPs modified with mannose maintained their physical properties almost unchanged after lyophilization. Additionally, the targeting specificity and immunogenicity remained unaffected. In contrast, even with the addition of cryoprotectants such as sucrose, the physical properties of LNPs were impaired, leading to an obvious decrease in immunogenicity. This may be attributed to the protective role of mannose on the surface of LNPs during lyophilization. Freshly prepared and lyophilized mLNP-circRNA vaccines elicited comparable immune responses in both the rabies virus model and the SARS-CoV-2 model. Our data demonstrated that mLNP-circRNA vaccines elicit robust immune responses while improving stability after lyophilization, with no compromise in tissue targeting specificity. Therefore, mannose-modified LNP-circRNA vaccines represent a promising vaccine design strategy.
Topics: RNA, Circular; Mannose; Vaccines; Immunity; Freeze Drying; RNA, Messenger
PubMed: 38078742
DOI: 10.1128/mbio.01775-23 -
Vaccine: X Dec 2023In a long-term immunogenicity study (1100 days post vaccination) in local Thai dogs the immune response of the oral rabies vaccine SPBN GASGAS was compared to those...
In a long-term immunogenicity study (1100 days post vaccination) in local Thai dogs the immune response of the oral rabies vaccine SPBN GASGAS was compared to those elicited by a commercial inactivated vaccine using immunobridging. Based on the detection of rabies virus binding (rVBA) and rabies virus neutralizing antibodies (rVNA) as measured by ELISA and Rapid Fluorescent Focus Inhibition Test (RFFIT) the long-term immune response in dogs vaccinated orally with the SPBNA GASGAS strain of rabies vaccine in a bait was non-inferior to a conventional inactivated rabies vaccine. The outcome of this study supports extending the originally claimed duration of immunity (DOI) of SPBN GASGAS after oral vaccination for dogs from 6 to 30 months.
PubMed: 38075432
DOI: 10.1016/j.jvacx.2023.100410 -
The Journal of General Virology Dec 2023The zoonotic rabies virus (RABV) is a non-segmented negative-sense RNA virus classified within the family , and is the most common aetiological agent responsible for...
The zoonotic rabies virus (RABV) is a non-segmented negative-sense RNA virus classified within the family , and is the most common aetiological agent responsible for fatal rabies disease. The RABV glycoprotein (G) forms trimeric spikes that protrude from RABV virions and mediate virus attachment, entry and spread, and is a major determinant of RABV pathogenesis. A range of RABV strains exist that are highly pathogenic in part due to their ability to evade host immune detection. However, some strains are disease-attenuated and can be cleared by host defences. A detailed molecular understanding of how strain variation relates to pathogenesis is currently lacking. Here, we reveal key differences in the trafficking profiles of RABV-G proteins from the challenge virus standard strain (CVS-11) and a highly attenuated vaccine strain SAD-B19 (SAD). We show that CVS-G traffics to the cell surface and undergoes rapid internalization through both clathrin- and cholesterol-dependent endocytic pathways. In contrast, SAD-G remains resident at the plasma membrane and internalizes at a significantly slower rate. Through engineering hybrids of CVS-G and SAD-G, we show that the cytoplasmic tail of CVS-G is the key determinant of these different internalization profiles. Alanine scanning further revealed that mutation of Y497 in CVS-G (H497 in SAD-G) could reduce the rate of internalization to SAD-G levels. Together, these data reveal new phenotypic differences between CVS-G and SAD-G proteins that may contribute to altered pathogenicity.
Topics: Humans; Rabies virus; Virus Internalization; Rabies; Rabies Vaccines; Glycoproteins; GTP-Binding Proteins
PubMed: 38063294
DOI: 10.1099/jgv.0.001935