Faculty Opinions recommendation of Investigation of the role of healthy dogs as potential carriers of rabies virus.

The author verified by experiment that the guinea pig skin is an organ highly sensitive to the rabies virus - infection with rabies through the skin is very easy, which the author puts in connection with its anatomical features (a rich network of nerves).

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Assessing the risks of intervention: immobilization, radio-collaring and vaccination of African wild dogs

Oryx ◽

10.1046/j.1365-3008.2001.00186.x ◽

2001 ◽

Vol 35 (3) ◽

pp. 234-244 ◽

Cited By ~ 6

Author(s):

Rosie Woodroffe

Keyword(s):

Rabies Virus ◽

Lycaon Pictus ◽

Full Data ◽

Serengeti Ecosystem ◽

African Wild Dogs ◽

Wild Dog ◽

Wild Dogs ◽

Rabies Vaccination ◽

Future Management

AbstractControversy has surrounded the role of intervention in studies of African wild dogs Lycaon pictus. Following the death or disappearance of all wild dogs under study in the Serengeti ecosystem, it was suggested that immobilization, radio-collaring or administration of rabies vaccines might have caused high mortality by compromising wild dogs′ immune response to rabies virus. Planning future management and research on wild dogs and other species demands an assessment of the risks associated with such intervention. This paper critically reviews the available evidence and concludes that it is extremely unlikely that intervention contributed to the extinction of wild dogs in the Serengeti ecosystem. A more likely scenario is that vaccination failed to protect wild dogs exposed to rabies virus. Radio-collaring is an important component of wild dog research; hence, the benefits of immobilization appear to outweigh the risks, as long as (i) research is orientated towards wild dog conservation, (ii) radiocollaring is followed up by efficient monitoring, (iii) the number of animals immobilized is kept to the minimum necessary to maintain scientific rigour, and (iv) full data on disease and genetics are collected from all immobilized animals. By contrast, rabies vaccination currently seems to confer few benefits, at least when a single dose of vaccine is given. Further research, on captive animals, is in progress to establish more effective protocols, and to assess the role that vaccination might play in future management of wild dog populations.

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Interferon-Inducible GTPase 1 Impedes the Dimerization of Rabies Virus Phosphoprotein and Restricts Viral Replication

Journal of Virology ◽

10.1128/jvi.01203-20 ◽

2020 ◽

Vol 94 (21) ◽

Author(s):

Bin Tian ◽

Yueming Yuan ◽

Yu Yang ◽

Zhaochen Luo ◽

Baokun Sui ◽

...

Keyword(s):

Viral Replication ◽

Viral Infection ◽

Rabies Virus ◽

Parasite Infection ◽

Major Public Health Problem ◽

Intracellular Parasite ◽

Neurotropic Virus ◽

Pathogen Invasion ◽

P Protein

ABSTRACT Rabies, caused by rabies virus (RABV), is an ancient zoonosis and still a major public health problem for humans, especially in developing countries. RABV can be recognized by specific innate recognition receptors, resulting in the production of hundreds of interferon-stimulated genes (ISGs), which can inhibit viral replication at different stages. Interferon-inducible GTPase 1 (IIGP1) is a mouse-specific ISG and belongs to the immunity-related GTPases (IRGs) family. IIGP is reported to constrain intracellular parasite infection by disrupting the parasitophorous vacuole membrane. However, the role of IIGP1 in restricting viral replication has not been reported. In this present study, we found that IIGP1 was upregulated in cells and mouse brains upon RABV infection. Overexpression of IIGP1 limited RABV replication in cell lines and reduced viral pathogenicity in a mouse model. Consistently, deficiency of IIGP1 enhanced RABV replication in different parts of mouse brains. Furthermore, we found that IIGP1 could interact with RABV phosphoprotein (P protein). Mutation and immunoprecipitation analyses revealed that the Y128 site of P protein is critical for its interaction with IIGP1. Further study demonstrated that this interaction impeded the dimerization of P protein and thus suppressed RABV replication. Collectively, our findings for the first reveal a novel role of IIGP1 in restricting a typical neurotropic virus, RABV, which will provide fresh insight into the function of this mouse-specific ISG. IMPORTANCE Interferon and its downstream products, ISGs, are essential in defending against pathogen invasion. One of the ISGs, IIGP1, has been found to constrain intracellular parasite infection by disrupting their vacuole membranes. However, the role of IIGP1 in limiting viral infection is unclear. In this study, we show that infection with a typical neurotropic virus, RABV, can induce upregulation of IIGP1, which, in turn, suppresses RABV by interacting with its phosphoprotein (P protein) and thus blocking the dimerization of P protein. Our study provides the first evidence that IIGP1 functions in limiting viral infection and provides a basis for comprehensive understanding of this important ISG.

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Dual Role of Toll-Like Receptor 7 in the Pathogenesis of Rabies Virus in a Mouse Model

Journal of Virology ◽

10.1128/jvi.00111-20 ◽

2020 ◽

Vol 94 (9) ◽

Author(s):

Zhaochen Luo ◽

Lei Lv ◽

Yingying Li ◽

Baokun Sui ◽

Qiong Wu ◽

...

Keyword(s):

Immune Response ◽

Mouse Model ◽

Immune Responses ◽

Rabies Virus ◽

Mouse Brain ◽

Early Stage ◽

Toll Like Receptor ◽

Innate Recognition ◽

Recognition Receptor

ABSTRACT Rabies, caused by rabies virus (RABV), is a fatal encephalitis in humans and other mammals, which continues to present a public health threat in most parts of the world. Our previous study demonstrated that Toll-like receptor 7 (TLR7) is essential in the induction of anti-RABV antibodies via the facilitation of germinal center formation. In the present study, we investigated the role of TLR7 in the pathogenicity of RABV in a mouse model. Using isolated plasmacytoid dendritic cells (pDCs), we demonstrated that TLR7 is an innate recognition receptor for RABV. When RABV invaded from the periphery, TLR7 detected viral single-stranded RNA and triggered immune responses that limited the virus’s entry into the central nervous system (CNS). When RABV had invaded the CNS, its detection by TLR7 led to the production of cytokines and chemokines and an increase the permeability of the blood-brain barrier. Consequently, peripheral immune cells, including pDCs, macrophages, neutrophils, and B cells infiltrated the CNS. While this immune response, triggered by TLR7, helped to clear viruses, it also increased neuroinflammation and caused immunopathology in the mouse brain. Our results demonstrate that TLR7 is an innate recognition receptor for RABV, which restricts RABV invasion into the CNS in the early stage of viral infection but also contributes to immunopathology by inducing neuroinflammation. IMPORTANCE Developing targeted treatment for RABV requires understanding the innate immune response to the virus because early virus clearance is essential for preventing the fatality when the infection has progressed to the CNS. Previous studies have revealed that TLR7 is involved in the immune response to RABV. Here, we establish that TLR7 recognizes RABV and facilitates the production of some interferon-stimulated genes. We also demonstrated that when RABV invades into the CNS, TLR7 enhances the production of inflammatory cytokines which contribute to immunopathology in the mouse brain. Taken together, our findings suggest that treatments for RABV must consider the balance between the beneficial and harmful effects of TLR7-triggered immune responses.

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High Prevalence and Diversity of Cephalosporin-Resistant Enterobacteriaceae Including Extraintestinal Pathogenic E. coli CC648 Lineage in Rural and Urban Dogs in Northwest Spain

Antibiotics ◽

10.3390/antibiotics9080468 ◽

2020 ◽

Vol 9 (8) ◽

pp. 468 ◽

Cited By ~ 2

Author(s):

Fátima Abreu-Salinas ◽

Dafne Díaz-Jiménez ◽

Isidro García-Meniño ◽

Pilar Lumbreras ◽

Ana María López-Beceiro ◽

...

Keyword(s):

High Risk ◽

Antimicrobial Resistance ◽

One Health ◽

Potential Role ◽

Multidrug Resistant ◽

E Coli ◽

Rural And Urban ◽

High Prevalence ◽

Healthy Dogs

The aim of this work was to assess the prevalence of extended spectrum-β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae in fecal samples recovered from rural and urban healthy dogs in Northwest Spain (Galicia) to identify potential high-risk clones and to molecularly characterize positive isolates regarding the genes coding for ESBL/pAmpC resistance and virulence. Thirty-five (19.6%) out of 179 dogs were positive for cephalosporin-resistant Enterobacteriaceae, including Escherichiacoli and Klebsiella pneumoniae (39 and three isolates, respectively). All the isolates were multidrug resistant, with high rates of resistance to different drugs, including ciprofloxacin (71.4%). A wide diversity of ESBL/pAmpC enzymes, as well as E. coli phylogroups (A, B1, C, D, E, F and clade I) were found. The eight isolates (20.5%) found to conform to the ExPEC status, belonged to clones O1:H45-clade I-ST770 (CH11-552), O18:H11-A-ST93-CC168 (CH11-neg), O23:H16-B1-ST453-CC86 (CH6-31), and O83:H42-F-ST1485-CC648 (CH231-58), with the latter also complying the uropathogenic (UPEC) status. The three K. pneumoniae recovered produced CTX-M-15 and belonged to the ST307, a clone previously reported in human clinical isolates. Our study highlights the potential role of both rural and urban dogs as a reservoir of high-risk Enterobacteriaceae clones, such as the CC648 of E. coli and antimicrobial resistance traits. Within a One-Health approach, their surveillance should be a priority in the fight against antimicrobial resistance.

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Interaction of the Rabies Virus P Protein with the LC8 Dynein Light Chain

Journal of Virology ◽

10.1128/jvi.74.21.10212-10216.2000 ◽

2000 ◽

Vol 74 (21) ◽

pp. 10212-10216 ◽

Cited By ~ 214

Author(s):

Hélène Raux ◽

Anne Flamand ◽

Danielle Blondel

Keyword(s):

Rabies Virus ◽

Light Chain ◽

Cytoplasmic Dynein ◽

Dynein Light Chain ◽

Directed Movement ◽

Virus Particles ◽

P Protein ◽

Infected Cells ◽

Transcription And Replication

ABSTRACT The rabies virus P protein is involved in viral transcription and replication but its precise function is not clear. We investigated the role of P (CVS strain) by searching for cellular partners by using a two-hybrid screening of a PC12 cDNA library. We isolated a cDNA encoding a 10-kDa dynein light chain (LC8). LC8 is a component of cytoplasmic dynein involved in the minus end-directed movement of organelles along microtubules. We confirmed that this molecule interacts with P by coimmunoprecipitation in infected cells and in cells transfected with a plasmid encoding P protein. LC8 was also detected in virus particles. Series of deletions from the N- and C-terminal ends of P protein were used to map the LC8-binding domain to the central part of P (residues 138 to 172). These results are relevant to speculate that dynein may be involved in the axonal transport of rabies virus along microtubules through neuron cells.

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