Research

22 pages, 7632 KiB

Open AccessArticle

Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation

by Yingying Li, Ling Zhao, Zhaochen Luo, Yachun Zhang, Lei Lv, Jianqing Zhao, Baokun Sui, Fei Huang, Min Cui, Zhen F. Fu and Ming Zhou

Viruses 2020, 12(4), 405; https://doi.org/10.3390/v12040405 - 06 Apr 2020

Cited by 18 | Viewed by 3794

Abstract

Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially [...] Read more.

Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-λ2 and IFN-λ3 could inhibit RABV replication in cells. To characterize the role of IFN-λ in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-λ2 or IFN-λ3, termed as rB2c-IFNλ2 or rB2c-IFNλ3, respectively, were constructed and rescued. It was found that expression of IFN-λ could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-λ could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-λ was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-λ in inhibiting RABV infection, which potentiates IFN-λ as a possible therapeutic agent for the treatment of RABV infection. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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12 pages, 5861 KiB

Open AccessArticle

Rabies in the African Civet: An Incidental Host for Lyssaviruses?

by Claude T. Sabeta, Denise A. Marston, Lorraine M. McElhinney, Daniel L. Horton, Baby M. N. Phahladira and Anthony R. Fooks

Viruses 2020, 12(4), 368; https://doi.org/10.3390/v12040368 - 27 Mar 2020

Cited by 8 | Viewed by 2999

Abstract

In South Africa, canid rabies virus (RABV) infection is maintained in domestic and wildlife species. The identification of rabies in African civets raised the question of whether this wildlife carnivore is a potential reservoir host of RABVs of direct and ancestral dog origin [...] Read more.

In South Africa, canid rabies virus (RABV) infection is maintained in domestic and wildlife species. The identification of rabies in African civets raised the question of whether this wildlife carnivore is a potential reservoir host of RABVs of direct and ancestral dog origin (dog-maintained and dog-derived origins) with an independent cycle of transmission. Genetic analyses of African civet nucleoprotein sequences for 23 African civet RABVs and historically published sequences demonstrated that RABVs from African civets have two origins related to dog and mongoose rabies enzootics. The data support observations of the interaction of civets with domestic dogs and wildlife mongooses, mostly in Northern South Africa and North-East Zimbabwe. Within each host species clade, African civet RABVs group exclusively together, implying intra-species virus transfer occurs readily. The canid RABV clade appears to support virus transfer more readily between hosts than mongoose RABVs. Furthermore, these data probably indicate short transmission chains with conspecifics that may be related to transient rabies maintenance in African civets. Hence, it is important to continue monitoring the emergence of lyssaviruses in this host. Observations from this study are supported by ongoing and independent similar cases, in which bat-eared foxes and black-backed jackal species maintain independent rabies cycles of what were once dog-maintained RABVs. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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24 pages, 7835 KiB

Open AccessArticle

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

by Vinod Sundaramoorthy, Nathan Godde, Ryan J. Farr, Diane Green, John M. Haynes, John Bingham, Carmel M. O’Brien and Megan Dearnley

Viruses 2020, 12(4), 359; https://doi.org/10.3390/v12040359 - 25 Mar 2020

Cited by 14 | Viewed by 4193

Abstract

Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons [...] Read more.

Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed to this knowledge gap. In this study, we utilize advances in stem cell technology to characterize rabies infection in human stem cell-derived neurons. We show key cellular features of rabies infection in our human neural cultures, including upregulation of inflammatory chemokines, lack of neuronal apoptosis, and axonal transmission of viruses in neuronal networks. In addition, we highlight specific differences in cellular pathogenesis between laboratory-adapted and field strain lyssavirus. This study therefore defines the first stem cell-derived ex-vivo model system to study rabies pathogenesis in human neurons. This new model system demonstrates the potential for enabling an increased understanding of molecular mechanisms in human rabies, which could lead to improved control methods. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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15 pages, 5178 KiB

Open AccessArticle

The Serological Prevalence of Rabies Virus-Neutralizing Antibodies in the Bat Population on the Caribbean Island of Trinidad

by Janine F. R. Seetahal, Lauren Greenberg, Panayampalli Subbian Satheshkumar, Manuel J. Sanchez-Vazquez, George Legall, Shamjeet Singh, Vernie Ramkissoon, Tony Schountz, Vincent Munster, Christopher A. L. Oura and Christine V. F. Carrington

Viruses 2020, 12(2), 178; https://doi.org/10.3390/v12020178 - 05 Feb 2020

Cited by 8 | Viewed by 3491

Abstract

Rabies virus (RABV) is the only lyssavirus known to be present within the Caribbean. The island of Trinidad, is richly diverse in chiropteran fauna and endemic for bat-transmitted rabies with low RABV isolation rates observed in this population. We aimed to determine the [...] Read more.

Rabies virus (RABV) is the only lyssavirus known to be present within the Caribbean. The island of Trinidad, is richly diverse in chiropteran fauna and endemic for bat-transmitted rabies with low RABV isolation rates observed in this population. We aimed to determine the seroprevalence of rabies virus neutralizing antibodies (RVNA) in light of spatio-temporal and bat demographic factors to infer the extent of natural exposure to RABV in the Trinidadian bat population. RVNA titers were determined by the RABV micro-neutralization test on 383 bat samples representing 21 species, comprising 30.9% of local bat diversity, from 31 locations across the island over 5 years. RVNA was positively detected in 33 samples (8.6%) representing 6 bat species (mainly frugivorous) with titers ranging from 0.1 to 19 IU/mL (mean 1.66 IU/mL). The analyses based on a multivariable binomial generalised linear mixed-effects model showed that bat age and year of capture were significant predictors of seropositivity. Thus, juvenile bats were more likely to be seropositive when compared to adults (estimate 1.13; p = 0.04) which may suggest early exposure to the RABV with possible implications for viral amplification in this population. Temporal variation in rabies seropositivity, 2012–2014 versus 2015–2017 (estimate 1.07; p = 0.03) may have been related to the prevailing rabies epizootic situation. Regarding other factors investigated, RVNA was found in bats from both rural and non-rural areas, as well as in both hematophagous and non-hematophagous bat species. The most common seropositive species, Artibeus jamaicensis planirostris is ubiquitous throughout the island which may potentially facilitate human exposure. The findings of this study should be factored into public health assessments on the potential for rabies transmission by non-hematophagous bats in Trinidad. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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14 pages, 1000 KiB

Open AccessArticle

Molecular Detection of Rabies Lyssaviruses from Dogs in Southeastern Nigeria: Evidence of TransboundaryTransmission of Rabies in West Africa

by Ukamaka U Eze, Ernest C Ngoepe, Boniface M Anene, Romanus C Ezeokonkwo, Chika I Nwosuh and Claude T Sabeta

Viruses 2020, 12(2), 134; https://doi.org/10.3390/v12020134 - 23 Jan 2020

Cited by 8 | Viewed by 3736

Abstract

Despite being the first country to register confirmed cases of Mokola and Lagos bat lyssaviruses (two very distant lyssaviruses), knowledge gaps, particularly on the molecular epidemiology of lyssaviruses, still exist in Nigeria. A total of 278 specimens were collected from dogs in southeastern [...] Read more.

Despite being the first country to register confirmed cases of Mokola and Lagos bat lyssaviruses (two very distant lyssaviruses), knowledge gaps, particularly on the molecular epidemiology of lyssaviruses, still exist in Nigeria. A total of 278 specimens were collected from dogs in southeastern Nigeria between October 2015 and July 2016, and 23 (8.3%) of these tested positive for lyssaviruses with the direct fluorescent antibody test (DFA). The lyssaviruses were genetically characterized by amplifying the highly conserved nucleoprotein (N) gene of the rabies lyssaviruses (RABVs) of the viral genome. Phylogenetic analyses of the nucleotide sequences showed that all the RABV sequences in this study were of the Africa-2 lineage. Our results demonstrated that transboundary transmission of rabies lyssavirus is a key event, given that one of the RABV sequences (MN196576) clustered with rabies variants from neighboring Niger Republic. Furthermore, three RABVs from dogs from Anambra State clustered separately forming a novel and distinct group. Our results demonstrated that transboundary transmission of RABLVs is a key driver in the spread of rabies in West Africa. In order for the successful control of this zoonotic disease, a multinational stepwise surveillance and elimination of rabies in Africa by 2030 is probably the solution for regional elimination. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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12 pages, 1413 KiB

Open AccessArticle

Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns

by Sten Calvelage, Marcin Smreczak, Anna Orłowska, Conrad Martin Freuling, Thomas Müller, Christine Fehlner-Gardiner, Susan Nadin-Davis, Dirk Höper and Paweł Trębas

Viruses 2020, 12(1), 115; https://doi.org/10.3390/v12010115 - 17 Jan 2020

Cited by 6 | Viewed by 2843

Abstract

Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and [...] Read more.

Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bern_orig)-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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13 pages, 1640 KiB

Open AccessArticle

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

by Amy J. Davis, Kathleen M. Nelson, Jordona D. Kirby, Ryan Wallace, Xiaoyue Ma, Kim M. Pepin, Richard B. Chipman and Amy T. Gilbert

Viruses 2019, 11(11), 1006; https://doi.org/10.3390/v11111006 - 31 Oct 2019

Cited by 20 | Viewed by 3233

Abstract

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case [...] Read more.

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (

\bar{ψ}

) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to

\bar{ψ}

of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from

\bar{ψ}

of 0.60 SE = 0.03 in the spring of 2006 to

\bar{ψ}

of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG^®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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14 pages, 998 KiB

Open AccessArticle

Cross-Protection of Inactivated Rabies Vaccines for Veterinary Use against Bat Lyssaviruses Occurring in Europe

by Alexandre Servat, Marine Wasniewski and Florence Cliquet

Viruses 2019, 11(10), 936; https://doi.org/10.3390/v11100936 - 11 Oct 2019

Cited by 3 | Viewed by 2811

Abstract

Human rabies vaccines have been shown to induce partial protection against members of phylogroup I bat lyssaviruses. Here, we investigated the capacity of a widely used rabies inactivated vaccine (Rabisin, Boehringer-Ingelheim) for veterinary use to cross-protect mice experimentally infected with European bat lyssavirus [...] Read more.

Human rabies vaccines have been shown to induce partial protection against members of phylogroup I bat lyssaviruses. Here, we investigated the capacity of a widely used rabies inactivated vaccine (Rabisin, Boehringer-Ingelheim) for veterinary use to cross-protect mice experimentally infected with European bat lyssavirus 1 (EBLV-1b), European bat lyssavirus 2 (EBLV-2), and Bokeloh bat lyssavirus (BBLV) occurring in Europe. For each lyssavirus, we investigated the efficacy of two different doses of vaccine against two viral doses administrated by either central or peripheral routes. In parallel, seroconversion following pre-exposure vaccination was investigated. In this study, we demonstrated that the three investigated bat isolates were pathogenic, even at low dose, when inoculated by the central route but were not/less pathogenic when administrated peripherally. The Rabisin vaccine was capable of significantly cross-protecting mice inoculated intramuscularly with EBLV-1b and EBLV-2 and intracerebrally with BBLV. The level of rabies neutralizing antibodies induced by the Rabisin was quite high against the bat lyssaviruses, but with no significant differences between immunization with 1 and 5 IU/dose. The study emphasizes that the quality of rabies-inactivated vaccines for veterinary use is of utmost importance to optimize the cross-protection of pets against phylogroup I bat lyssaviruses occurring in Europe. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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12 pages, 720 KiB

Open AccessArticle

Long-Term Immunogenicity and Efficacy of the Oral Rabies Virus Vaccine Strain SPBN GASGAS in Foxes

by Conrad M. Freuling, Verena te Kamp, Antonia Klein, Maria Günther, Luca Zaeck, Madlin Potratz, Elisa Eggerbauer, Katharina Bobe, Christian Kaiser, Antje Kretzschmar, Steffen Ortmann, Peter Schuster, Adriaan Vos, Stefan Finke and Thomas Müller

Viruses 2019, 11(9), 790; https://doi.org/10.3390/v11090790 - 27 Aug 2019

Cited by 13 | Viewed by 3673

Abstract

To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = [...] Read more.

To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (10^6.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (10^3.0 MICLD₅₀/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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10 pages, 7464 KiB

Open AccessArticle

Evaluation of an Immunochromatographic Assay as a Canine Rabies Surveillance Tool in Goa, India

by Gowri Yale, Andrew D. Gibson, Reeta S. Mani, Harsha P. K., Niceta Cunha Costa, Julie Corfmat, Ilona Otter, Nigel Otter, Ian G. Handel, Barend Mark Bronsvoort, Richard J. Mellanby, Santosh Desai, Vilas Naik, Luke Gamble and Stella Mazeri

Viruses 2019, 11(7), 649; https://doi.org/10.3390/v11070649 - 15 Jul 2019

Cited by 19 | Viewed by 5007

Abstract

Rabies is a fatal zoonotic disease transmitted by the bite of a rabid animal. More than 95% of the human rabies cases in India are attributed to exposure to rabid dogs. This study evaluated the utility of a lateral flow immunochromatographic assay (LFA) [...] Read more.

Rabies is a fatal zoonotic disease transmitted by the bite of a rabid animal. More than 95% of the human rabies cases in India are attributed to exposure to rabid dogs. This study evaluated the utility of a lateral flow immunochromatographic assay (LFA) (Anigen Rapid Rabies Ag Test Kit, Bionote, Hwaseong-si, Korea) for rapid post mortem diagnosis of rabies in dogs. Brain tissue was collected from 202 animals that were screened through the Government of Goa rabies surveillance system. The brain tissue samples were obtained from 188 dogs, nine cats, three bovines, one jackal and one monkey. In addition, 10 dogs that died due to trauma from road accidents were included as negative controls for the study. The diagnostic performance of LFA was evaluated using results from direct fluorescence antibody test (dFT); the current gold standard post mortem test for rabies infection. Three samples were removed from the analysis as they were autolysed and not fit for testing by dFT. Of the 209 samples tested, 117 tested positive by LFA and 92 tested negative, while 121 tested positive by dFT and 88 tested negative. Estimates of LFA sensitivity and specificity were 0.96 (95% CI 0.91–0.99) and 0.99 (95% CI 0.94–1.00), respectively. The LFA is a simple and low-cost assay that aids in the rapid diagnosis of rabies in the field without the need for expensive laboratory equipment or technical expertise. This study found that Bionote LFA has potential as a screening tool in rabies endemic countries. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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Review

Jump to: Research, Other

20 pages, 7687 KiB

Open AccessReview

Transcriptional Control and mRNA Capping by the GDP Polyribonucleotidyltransferase Domain of the Rabies Virus Large Protein

by Tomoaki Ogino and Todd J. Green

Viruses 2019, 11(6), 504; https://doi.org/10.3390/v11060504 - 01 Jun 2019

Cited by 14 | Viewed by 5412

Abstract

Rabies virus (RABV) is a causative agent of a fatal neurological disease in humans and animals. The large (L) protein of RABV is a multifunctional RNA-dependent RNA polymerase, which is one of the most attractive targets for developing antiviral agents. A remarkable homology [...] Read more.

Rabies virus (RABV) is a causative agent of a fatal neurological disease in humans and animals. The large (L) protein of RABV is a multifunctional RNA-dependent RNA polymerase, which is one of the most attractive targets for developing antiviral agents. A remarkable homology of the RABV L protein to a counterpart in vesicular stomatitis virus, a well-characterized rhabdovirus, suggests that it catalyzes mRNA processing reactions, such as 5′-capping, cap methylation, and 3′-polyadenylation, in addition to RNA synthesis. Recent breakthroughs in developing in vitro RNA synthesis and capping systems with a recombinant form of the RABV L protein have led to significant progress in our understanding of the molecular mechanisms of RABV RNA biogenesis. This review summarizes functions of RABV replication proteins in transcription and replication, and highlights new insights into roles of an unconventional mRNA capping enzyme, namely GDP polyribonucleotidyltransferase, domain of the RABV L protein in mRNA capping and transcription initiation. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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Other

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11 pages, 1268 KiB

Open AccessBrief Report

Serological Survey of Lyssaviruses in Polish Bats in the Frame of Passive Rabies Surveillance Using an Enzyme-Linked Immunosorbent Assay

by Anna Orłowska, Marcin Smreczak, Conrad Martin Freuling, Thomas Müller, Paweł Trębas and Jerzy Rola

Viruses 2020, 12(3), 271; https://doi.org/10.3390/v12030271 - 28 Feb 2020

Cited by 4 | Viewed by 2895

Abstract

Background: Bats are known to host a number of nonpathogenic viruses, as well as highly pathogenic viruses causing fatal diseases like rabies. Serological surveys as part of active and passive bat rabies surveillance mainly use seroneutralization assays, demonstrating the presence of lyssavirus-specific [...] Read more.

Background: Bats are known to host a number of nonpathogenic viruses, as well as highly pathogenic viruses causing fatal diseases like rabies. Serological surveys as part of active and passive bat rabies surveillance mainly use seroneutralization assays, demonstrating the presence of lyssavirus-specific antibodies in a variety of European bats, particularly against European bat lyssaviruses type 1 (EBLV-1). Here, we present the first serological survey in European bats of this kind during which European bats from Poland collected in the frame of passive rabies surveillance between 2012 and 2018, as well as Serotine bats (Eptesicus serotinus) and North American Big Brown bats (Eptesicus fuscus) from previous experimental studies, were tested using a commercial ELISA kit for the detection of anti-lyssavirus antibodies. Results: Lyssavirus-specific antibodies were detected in 35 (30.4%) out of 115 Polish bats of both sexes, representing nine out of 13 identified bat species endemic mainly to Central Southern Europe and Western Asia, i.e., Eptesicus serotinus, Nyctalus noctula, Myotis daubentonii, Plecotus auritus, Vespertillo murinus,Pipistrellus pipistrellus, Pipistrellus pipilstrellus/Pipistrellus pygmaeus, Myotis brandtii, and Barbastella barbastellus. Seroprevalence was highest in bat species of Nyctalus noctula, Eptesicus serotinus, Plecotus auritus, and Myotis daubentonii. More than 60% of the ELISA seropositive bats originated from the voivodeships of Silesia, Lower-Silesian, Warmian-Mazurian, and Mazowian. Rabies-specific antibodies were also found in Eptesicus fuscus bats from North America. Conclusions: The study demonstrates the principal application of the BioPro Rabies ELISA Ab Kit for the detection of anti-lyssavirus specific antibodies in body fluids and serum samples of bats. However, results may only be reliable for North American bats, whereas interpretation of results for European bats per se is difficult because proper validation of the test is hampered by the protected status of these species. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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11 pages, 2057 KiB

Open AccessCase Report

Using the LN34 Pan-Lyssavirus Real-Time RT-PCR Assay for Rabies Diagnosis and Rapid Genetic Typing from Formalin-Fixed Human Brain Tissue

by Rene Edgar Condori, Michael Niezgoda, Griselda Lopez, Carmen Acosta Matos, Elinna Diaz Mateo, Crystal Gigante, Claire Hartloge, Altagracia Pereira Filpo, Joseph Haim, Panayampalli Subbian Satheshkumar, Brett Petersen, Ryan Wallace, Victoria Olson and Yu Li

Viruses 2020, 12(1), 120; https://doi.org/10.3390/v12010120 - 18 Jan 2020

Cited by 9 | Viewed by 3470

Abstract

Human rabies post mortem diagnostic samples are often preserved in formalin. While immunohistochemistry (IHC) has been routinely used for rabies antigen detection in formalin-fixed tissue, the formalin fixation process causes nucleic acid fragmentation that may affect PCR amplification. This study reports the diagnosis [...] Read more.

Human rabies post mortem diagnostic samples are often preserved in formalin. While immunohistochemistry (IHC) has been routinely used for rabies antigen detection in formalin-fixed tissue, the formalin fixation process causes nucleic acid fragmentation that may affect PCR amplification. This study reports the diagnosis of rabies in an individual from the Dominican Republic using both IHC and the LN34 pan-lyssavirus real-time RT-PCR assay on formalin-fixed brain tissue. The LN34 assay generates a 165 bp amplicon and demonstrated higher sensitivity than traditional PCR. Multiple efforts to amplify nucleic acid fragments larger than 300 bp using conventional PCR were unsuccessful, probably due to RNA fragmentation. Sequences generated from the LN34 amplicon linked the case to the rabies virus (RABV) strain circulating in the Ouest Department of Haiti to the border region between Haiti and the Dominican Republic. Direct sequencing of the LN34 amplicon allowed rapid and low-cost rabies genetic typing. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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5 pages, 662 KiB

Open AccessPerspective

Current Rabies Vaccines Do Not Confer Protective Immunity against Divergent Lyssaviruses Circulating in Europe

by Juan E. Echevarría, Ashley C. Banyard, Lorraine M. McElhinney and Anthony R. Fooks

Viruses 2019, 11(10), 892; https://doi.org/10.3390/v11100892 - 24 Sep 2019

Cited by 11 | Viewed by 3831

Abstract

The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive [...] Read more.

The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent lyssaviruses. The presence in European indigenous bats of recently described lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances. Full article

(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)

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