scholarly journals The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

2016 ◽  
Author(s):  
Zi Li ◽  
Wenqi He ◽  
Yungang Lan ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
...  
Keyword(s):  
Nervous System ◽  
Cause Of Death ◽  
Viral Infections ◽  
Vaccine Development ◽  
Wild Strain ◽  
Effective Vaccine ◽  
Symptoms Of Depression ◽  
Encephalomyelitis Virus ◽  
Cns Dysfunction ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%-99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

scholarly journals The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2443 ◽  
Author(s):  
Zi Li ◽  
Wenqi He ◽  
Yungang Lan ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
...  
Keyword(s):  
Nervous System ◽  
Cause Of Death ◽  
Viral Infections ◽  
Vaccine Development ◽  
Wild Strain ◽  
Effective Vaccine ◽  
Symptoms Of Depression ◽  
Encephalomyelitis Virus ◽  
Cns Dysfunction ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

scholarly journals The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

2016 ◽  
Author(s):  
Zi Li ◽  
Wenqi He ◽  
Yungang Lan ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
...  
Keyword(s):  
Nervous System ◽  
Cause Of Death ◽  
Viral Infections ◽  
Vaccine Development ◽  
Wild Strain ◽  
Effective Vaccine ◽  
Symptoms Of Depression ◽  
Encephalomyelitis Virus ◽  
Cns Dysfunction ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%-99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

scholarly journals Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Recombinant Dna ◽  
Vaccine Development ◽  
The Body ◽  
Effective Vaccine ◽  
Subunit Vaccines ◽  
Simplex Virus ◽  
Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

scholarly journals AN OVERVIEW OF RECOMBINANT VACCINE TECHNOLOGY, ADJUVANTS AND VACCINE DELIVERY METHODS

2016 ◽  
Vol 8 (11) ◽  
pp. 19 ◽  
Author(s):  
Shuaibu Abdullahi Hudu ◽  
Saadatu Haruna Shinkafi ◽  
Shuaibu Umar
Keyword(s):  
Viral Infections ◽  
Vaccine Development ◽  
Journal Article ◽  
Vaccine Delivery ◽  
Recombinant Vaccine ◽  
Effective Vaccine ◽  
Routes Of Administration ◽  
Life Threatening ◽  
New Generation ◽  
And Control

Development of an effective vaccine is of paramount important in disease prevention and control. As such, recombinant technology can serve as a gateway for the development of safe and effective vaccines that can be delivered effectively with an appropriate adjuvant. Therefore, this paper aimed to review the role of recombinant vaccine technology, new adjuvants and the challenge of vaccine delivery. Related peer-reviewed journal article searches were conducted using a subscribed database at the Universiti Putra Malaysia library, involving areas of Health Sciences and Medicine via Medline, SCOPUS and Google Scholar. New generation vaccines include highly purified synthetic or recombinant antigens that stimulate effective cell-mediated immune and mucosal immunity. In order to enhance their efficacy, a number of adjuvants are used. Efforts have also been made to explore the usage of non-invasive routes of administration, devices and equipment for optimized antigen and immune-potentiator delivery of the immune system. Recombinant vaccine technology is rapid, compared to the traditional method of vaccine development and does not require the handling of live viruses. It is, therefore, a promising technology for developing a future vaccine to curb emerging and re-emerging viral infections that may be life-threatening or teratogenic.

scholarly journals Ulk1 Governs Nerve Growth Factor/TrkA Signaling by Mediating Rab5 GTPase Activation in Porcine Hemagglutinating Encephalomyelitis Virus-Induced Neurodegenerative Disorders

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Zi Li ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
Yungang Lan ◽  
Shiyu Hu ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Progressive Failure ◽  
Neurological Dysfunction ◽  
Long Distance ◽  
Nerve Growth ◽  
Encephalomyelitis Virus ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

ABSTRACT Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus and causes neurological dysfunction in the central nervous system (CNS), but the neuropathological mechanism of PHEV remains poorly understood. We report that Unc51-like kinase 1 (Ulk1/Unc51.1) is a pivotal regulator of PHEV-induced neurological disorders and functions to selectively control the initiation of nerve growth factor (NGF)/TrkA endosome trafficking. We first identified the function of Ulk1 by histopathologic evaluation in a PHEV-infected mouse model in which neuronal loss was accompanied by the suppression of Ulk1 expression. Morphogenesis assessments in the primary cortical neurons revealed that overexpression or mutations of Ulk1 modulated neurite outgrowth, collateral sprouting, and endosomal transport. Likewise, Ulk1 expression was decreased following PHEV infection, suggesting that there was a correlation between the neurodegeneration and functional Ulk1 deficiency. We then showed that Ulk1 forms a multiprotein complex with TrkA and the early endosome marker Rab5 and that Ulk1 defects lead to either blocking of NGF/TrkA endocytosis or premature degradation of pTrkA via constitutive activation of the Rab5 GTPase. Further investigation determined that the ectopic expression of Rab5 mutants induces aberrant endosomal accumulation of activated pTrkA, proving that targeting of Ulk1-TrkA-NGF signaling to the retrograde transport route in the neurodegenerative process that underlies PHEV infection is dependent on Rab5 GTPase activity. Therefore, we described a long-distance signaling mechanism of PHEV-driven deficits in neurons and suggested that such Ulk1 repression may result in limited NGF/TrkA retrograde signaling within activated Rab5 endosomes, explaining the progressive failure of neurite outgrowth and survival. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus and targets neurons in the nervous system for proliferation, frequently leaving behind grievous neurodegeneration. Structural plasticity disorders occur in the axons, dendrites, and dendritic spines of PHEV-infected neurons, and dysfunction of this neural process may contribute to neurologic pathologies, but the mechanisms remain undetermined. Further understanding of the neurological manifestations underlying PHEV infection in the CNS may provide insights into both neurodevelopmental and neurodegenerative diseases that may be conducive to targeted approaches for treatment. The significance of our research is in identifying an Ulk1-related neurodegenerative mechanism, focusing on the regulatory functions of Ulk1 in the transport of long-distance trophic signaling endosomes, thereby explaining the progressive failure of neurite outgrowth and survival associated with PHEV aggression. This is the first report to define a mechanistic link between alterations in signaling from endocytic pathways and the neuropathogenesis of PHEV-induced CNS disease.

scholarly journals Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Zi Li ◽  
Kui Zhao ◽  
Yungang Lan ◽  
Xiaoling Lv ◽  
Shiyu Hu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Entry ◽  
Intracellular Trafficking ◽  
Neural Cells ◽  
Dependent Manner ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Ph Dependent ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

ABSTRACT Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis. To verify the roles of distinct endocytic pathways, systematic approaches were used, including pharmacological inhibition, RNA interference, confocal microscopy analysis, use of fluorescently labeled virus particles, and overexpression of a dominant negative (DN) mutant. Quantification of infected cells showed that PHEV enters cells by clathrin-mediated endocytosis (CME) and that low pH, dynamin, cholesterol, and Eps15 are indispensably involved in this process. Intriguingly, PHEV invasion leads to rapid actin rearrangement, suggesting that the intactness and dynamics of the actin cytoskeleton are positively correlated with viral endocytosis. We next investigated the trafficking of internalized PHEV and found that Rab5- and Rab7-dependent pathways are required for the initiation of a productive infection. Furthermore, a GTPase activation assay suggested that endogenous Rab5 is activated by PHEV and is crucial for viral progression. Our findings demonstrate that PHEV hijacks the CME and endosomal system of the host to enter and traffic within neural cells, providing new insights into PHEV pathogenesis and guidance for antiviral drug design. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV), a nonsegmented, positive-sense, single-stranded RNA coronavirus, invades the central nervous system (CNS) and causes neurological dysfunction. Neural cells are its targets for viral progression. However, the detailed mechanism underlying PHEV entry and trafficking remains unknown. PHEV is the etiological agent of porcine hemagglutinating encephalomyelitis, which is an acute and highly contagious disease that causes numerous deaths in suckling piglets and enormous economic losses in China. Understanding the viral entry pathway will not only advance our knowledge of PHEV infection and pathogenesis but also open new approaches to the development of novel therapeutic strategies. Therefore, we employed systematic approaches to dissect the internalization and intracellular trafficking mechanism of PHEV in Neuro-2a cells. This is the first report to describe the process of PHEV entry into nerve cells via clathrin-mediated endocytosis in a dynamin-, cholesterol-, and pH-dependent manner that requires Rab5 and Rab7.

scholarly journals A CRITICAL APPRAISAL ON IMMUNOMODULATION AND BATTLE AGAINST COVID-19: AN EVIDENCE BASED PREVENTIVE AYURVEDIC APPROACH

AYUSHDHARA ◽  
2020 ◽  
pp. 2656-2670
Author(s):  
Masand Sameet ◽  
Thakur Jyotsna
Keyword(s):  
Viral Infections ◽  
Vaccine Development ◽  
Biological Activities ◽  
Time Lag ◽  
Effective Vaccine ◽  
Evidence Based ◽  
Positive Health ◽  
Highly Pathogenic ◽  
The World ◽  
Prohibitive Cost

The emergence of SARSCOV-2 has been noticed as the third introduction of a highly pathogenic corona virus into the human population after SARS-COV and MERV-COV in 21st century. It has posed a horrible situation that warrants urgent global attention due to the emergence of more virulent viral strain, predicted future viral mutations, prohibitive cost of available drugs, time lag between vaccine development and mass causalities occurring all over the world. Although specific antiviral vaccine is the effective solution but a potent and comprehensive immune response to maintain homeostasis is also critical for prophylactic as well as therapeutic management of the disease. Amidst all the gloom spread due to this outbreak, everyone is focusing on preventive measures until an effective vaccine is developed. Ayurveda- An holistic science offers a plethora of preventive therapies to enhance body’s resistance against infections. It is evident that nutritional and herbal approaches taken together provide potent tools for controlling an array of viral infections and have been effectively used by humans all over the world since ages during such outbreaks. Ayurveda and yoga have great potential for embracing the world in creating a more positive health abode. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing this pandemic. This review portrays an eclectic overview for the preventive management of COVID-19 pandemic covering the dietary, lifestyle and herbal evidence based approaches that may be most likely helpful in managing the current pandemic scenario and also strengthens our body to cope-up with the next pandemic that might appear in not too distant future.

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