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Flaviviruses are a group of enveloped viruses that enter the host cells through receptor-mediated endocytosis. The entry of flaviviruses into the cells is a multi-step process which involves several host factors that trigger the uptake of the virus. The initial step in the virus life cycle is the interactions between viral envelope proteins and the specific receptors on the surface of host cell. To date, several receptors have been identified such as glycosaminoglycans, tight junction proteins, laminin receptor and phosphatidylserine receptors. Moreover, the viruses may utilize integrins and C-type lectin receptors on the surface of host cells as the initial attachment factors. This mini-review will focus on recent progresses in the understanding of virus attachment, internalization, and membrane fusion with specific emphasis on the cellular receptors.

The role of TANK-binding kinase 1 (TBK1) of humans and mice in innate immunity is well elucidated. Still, the molecular characterization and biological function of the TBK1 gene in herbivorous animals are less studied. Here, the open reading frame (ORF) of TBK1 of the cow and goat was firstly cloned and successfully expressed. The Phylogenetic tree analysis reveals that the TBK1 gene of goats and cows is similar to chicken and mute swans, respectively. Some evolutionary distances of the TBK1 gene were still present among different species. A slightly subcellular distribution difference was observed among full-length and truncated TBK1 of goats and cows. Dual-luciferase reporter assay has shown that the full-length TBK1 of goats and cows plays a vital role in the induction of IFN-β production. The viral infection experiment showed that the over-expression of the full-length TBK1 gene of the cow and goat significantly suppresses intracellular viral replication of the Lumpy skin disease virus (LSDV) in infected cells. Our study showed that TBK1 in the cows and goats is a crucial immunoregulatory for IFN-β production during viral infection, contributing to a better understanding of innate immunity in the herbivorous animal.

Influences of intermittent light regime as a tool to enhance egg production, egg quality, and blood parameters of laying hens were investigated. A total of 270 hens of Rhode Island Red (during 20 to 36 wk of age) were used to investigate the effects of intermittent light regime in completely randomized design. The birds were divided into 3 equal groups (6 replicates of 15 birds each) and housed in floor pens. The first group was served as non-treated control (C) and was exposed to continuous and constant light for 16 h light/day throughout the experimental period. Whereas, birds of the other groups were exposed to intermittent lights for 20 min/h + 40 min of constant light (T1; FLASH20) and 40 min/h + 20 min of constant light (T2; FLASH40) during the 16 h of light period. Hens of T1 group showed significantly (P ≤ 0.05) the highest concentration of total antioxidant capacity and the lowest one of malondialdehyde in comparison with the other groups. Hens of T1 group had significantly (P ≤ 0.05) the greatest egg laying rate and egg mass in comparison with the other counterparts. Feed consumption was similar in the groups under study. Hens exposed to FLASH20 had the lowest (P ≤ 0.05) FCR when compared with the other treatments. Eggs produced from hens exposed to FLASH20 had the highest value of shell thickness followed by the control and then that of those exposed to FLASH40. There were insignificant differences among the treatments in body weight of hens and all of other egg quality and egg problem traits. In conclusion, intermittent light regime of 20 min/h was the most efficient in comparison with the other ones. Finally, intermittent light regime of 20 min/h during laying period (during 20 to 36 wk of age) is highly recommended.

Autophagy triggered by glycoprotein-mediated membrane fusion has been reported for several paramyxoviruses. However, the function of HN and F glycoproteins of NDV and their role in autophagy induction have not been studied. Here, we found that co-transfection of HN and F of virulent NDV rapidly induced syncytium formation and triggered a steady state autophagy flux in adenocarcinomic human alveolar basal epithelial (A549) cells and chicken embryo fibroblast (DF-1) cells. Furthermore, we clearly identified that F and HN synergistically induced autophagosome fusion with lysosomes for subsequent degradation. The seven cleavage site mutations of F significantly decreased the autophagy induction, compared with those of wildtype virulent F. RNAi and pharmacological experiments suggested that autophagy benefitted membrane fusion and syncytium formation induced by F and HN of NDV. Activated F1 co-operated with HN to stimulate AMPK kinase and downstream ULK1 activation to suppress mTORC1 signaling. Our data described the synergistic role of HN and F in the induction of completed autophagic flux through the activation of AMPK- mTORC1- ULK1 pathway.

The present study aimed to investigate the influence of feed form and the level of dietary crude protein (CP) on the growth performance and carcass traits of growing geese. A total of 180 Egyptian geese (1 wk old) were randomly divided into 9 groups (20 chicks per group). Each group was subdivided into five replicates, with 4 birds per replicate. A 3 × 3 factorial experiment was performed with 3 types of diets (pellets, crumble, and mash) and 3 levels of dietary CP (22%, 20%, and 18% during the starter period and 20%, 18%, and 16% during the finisher period). The type of feed had significant (P ≤ 0.05) effects on body weight, body weight gain (ADG), the feed conversion ratio (FCR), and the protein efficiency ratio (PER) during all experimental periods, except ADG and PER from the 8th to 12th week. Dietary CP levels had significant effects on feed consumption (FC), FCR, and PER (p < 0.05 or 0.01) except from the 1st to 7th week for FC, 8th to 12th week for FCR, and 1st to 7th week for PER. Carcass, liver, heart, dressing, and wings (%) were found to be significantly (P < 0.01) improved in geese fed pellets compared to geese fed other types of diets. Birds fed a high-CP diet featured the highest (P < 0.05) values for liver, gizzard, heart, and giblets compared to the other groups at 12 wk of age. In conclusion, the present findings show that pellet and crumble feed are better than mash feed for promoting the growth of growing geese from the 1st to 12th week of age. The optimal dietary CP requirements for growing geese from the 1st to 7th and 8th to 12th weeks of age are 18% and 16%, respectively.

Floor type management is an important factor in turkey production in hot climates exceeding 30°C. In this study, a total of 360 turkeys aged 4 wk were randomly distributed to investigate growth performance, carcass characteristics, certain health aspects (breast blisters score, footpad burns, hock discoloration, and plumage condition), and airborne conditions. Birds in the first group were raised on a littered floor (control; C), whereas birds in the other groups (T1, T2, T3, T4, and T5) were raised on cement, wire net, rubber mat, plastic and wooden slatted floors, respectively. The results indicated that growth performance and meat quality were improved, with increases in body weight, daily body weight gain, feed conversion ratio, and tenderness and juiciness values, when plastic and wooden slatted floors were used. Moreover, the use of plastic and wooden slatted floors attenuated body temperature, airborne dust particulates, and ammonia concentrations. In conclusion, placing plastic, wooden slatted, or wire floors reduced the incidence of health disorders and alleviated heat stress effects by decreasing body temperature and the heterophil to lymphocyte ratio. Thus, plastic and wooden slatted floors are suitable for growing turkeys under the conditions of this study.

Background: Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND), which is particularly characterized by extensive pathologies in the digestive, respiratory and nervous systems. ND cause heavy economic losses to the world poultry industry by decreasing growth rate, decrease egg productions, mortality and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading decrease growth rate. Methods: In this study, we report the damage caused by the NDV infection in the pancreas of vaccinated as well specific pathogen free chickens. Results: The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Conclusion: Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

This study investigated the impact of supplementing normal and high-fat diets with graded levels of lycopene on the growth performance, cholesterol level of the muscle, and antioxidant markers in Japanese quail. A total of 192, 14 day-old unsexed Japanese quail were part of a 2 x 4 factorial arrangement consisting of a control group; birds that were fed a normal fat diet (NFD), another control group; birds that were fed a high-fat diet (HFD) with four levels of lycopene for NFD and HFD (0, 100, 200 and 300mg lycopene/kg diet). Lycopene level of 300mg/kg gave the greatest body weight, body weight gain, and relative growth rate when added to the NFD, but this level showed non-significant improvement in growth performance when supplemented to an HFD. Superoxide dismutase in the muscle and liver was noted to be high in NFD+ 300mgL, HFD+ 200mgL, and HFD+ 300mgL groups, while malondialdehyde level in the muscle and liver and cholesterol level in the muscle was found to be low in the same groups. Lycopene slightly improved growth performance, but significantly improved the antioxidant status and lowered cholesterol concentration in the muscle. A diet supplemented with 300 mg lycopene/kg could be recommended for Japanese quail.

This investigation studied the effects of different feed withdrawal times, water temperatures, and their interaction on growth performance, carcass traits, blood parameters, and health aspects of native turkeys (Egyptian local breed). We distributed native turkey poults (n = 180; 4 wk old) into 3 groups according to feed withdrawal time (ad libitum; feed withdrawal from 800 to 1,400 h, FW8 to 14; and feed withdrawal from 1,400 to 2,000 h, FW14 to 20). Each group was further divided into 2 subgroups corresponding to water temperature (ordinary and chilled water). Our results indicated that birds of FW14 to 20 exhibited the highest (P = 0.0001) body weight (BW) and average daily gain (ADG), whereas turkeys that drank chilled water displayed a higher BW than those that drank ordinary water. Turkeys that were kept under FW8 to 14 and drank chilled water displayed the highest BW at marketing and ADG from 4 to 16 wk of age. The lowest feed conversion ratio (FCR) was exhibited in turkeys kept off feed under the FW14 to 20 regime. Birds that were kept under FW14 to 20 and received chilled water showed the lowest FCR. The meat color scores of the birds that drank chilled water were higher than those that drank ordinary water, whereas birds kept off feed under the FW14 to 20 regime displayed the highest tenderness and juiciness, followed by those fed ad libitum. Turkeys reared under FW14 to 20 exhibited the highest albumin/globulin ratio and glucose content but the lowest globulin and aspartate transaminase (AST) values. Birds that were kept under FW14 to 20 and drank chilled water displayed the lowest corticosterone concentration. Turkeys reared under FW14 to 20 presented the lowest body temperature. Birds that drank chilled water exhibited a lower body temperature than those that drank ordinary water. Turkeys that were fed ad libitum and drank chilled water displayed the lowest body temperature. Conclusively, applying feed withdrawal and cold water had benefits in turkeys during heat stress. Applying these treatments as managerial alternatives for raising native turkeys during the summer season is highly recommended.

This experiment was conducted to observe the effects of varying swimming times (ST) of Muscovy ducks, raised in an open-sided house, in alleviating the deleterious effects of high temperature in hotter times of the day in the summer season on growth performance (body weight, average daily gain, feed consumption, and feed conversion ratio), carcass characteristics, body temperature, and some health aspects. We hypothesized that swimming times during the hottest periods of the day would show different performances. To test this hypothesis a total of 180 Muscovy ducklings were randomly distributed into 4 equal groups in a completely randomized design experiment. All groups were raised under similar housing conditions. Birds of the first group (C) were raised in the indoor system and had no access to a swimming pond. While all birds of the second, third, and fourth groups (T1, T2, and T3) had access to a swimming pond during 10:00 to 12:00 h, 12:00 to 14:00 h, and 14:00 to 16:00 h, respectively. The swimming pond (dimensions of 30 m length × 10 m width × 3 m depth with cement floor) was located in the front of the house. Vaccination and medical programs were undertaken according to the different ages under supervision of a licensed veterinarian. The obtained results indicated that swimming during 12:00 to 14:00 h improved (P 0.05) growth performance, dressed carcass, meat tenderness, lymphocyte, heterophils/lymphocytes ratio, body temperature, and mortality rate of Muscovy ducks. However, bone measurement, plumage conditions, foot pad dermatitis, hock discoloration, breast blisters score, and blood hematocrit values were insignificantly better in the group with access to the swimming pond during 12:00 to 14:00 h. In conclusion, raising ducks during hot conditions in an open-sided house with access to a swimming pond at 12:00 to 14:00 h is highly recommended due to the high BW, better immunity, decreased mortality rate, and low body temperature of ducks which was positively reflected in the health condition.

The genotype VII Newcastle disease virus (NDV) vaccine has begun to replace the traditional genotype II NDV vaccine and is widely used in the commercial poultry of China. However, the effect of homologous and heterogeneous anti-NDV serum on the evolution of prevalent NDV is unknown. To understand the effect of genotype II and VII anti-NDV serum on the evolution of genotype VII NDV strains, ZJ1 (waterfowl origin) and CH/SD/2008/128 (ND128; chicken origin) were used for serial passage of 30 generations in DF-1 cells without anti-NDV serum or with genotype II and VII anti-NDV serum independently. The F and HN genes of the 2 viruses were amplified for the 10th, 20th, and 30th generations of each serial passage group and compared with their respective original viruses. We found that there was only one mutation at position 248 in the F gene of ZJ1 due to the serum pressure of genotype VII anti-NDV. Similarly, mutations at residue 527 of the F gene, and position 9 and 319 of the HN gene of ND128 were noted in both anti-NDV serum groups. The results show that the nonsynonymous (NS)-to-synonymous (S) ratio of the F gene of ZJ1 virus was 1.6, and for the HN gene, it was 2.5 in the anti-II serum group. In the anti-VII serum group, the NS/S ratio for the F gene was 2.1, and for the HN gene, it was 2.5. The NS/S ratio of the F gene of the ND128 virus was 0.8, and for the HN gene, it was 3 in the anti-II serum group. Furthermore, the NS/S ratio of the F gene was 0.8, and the HN gene was 2.3 in the anti-VII group. Taken together, our findings highlight that there was no significant difference in the variation of protective antigens in genotype VII NDV under the selection pressure of homologous and heterogeneous genotype NDV inactivated vaccines.

Mast cells (MCs) are granulated cells of haematopoietic lineage and constitute a major sensory arm of the immune system. MCs dually guard hosts and regulate immune responses against invading pathogens. This property of the MCs is attributed to their adaptability to detect stress signals and pathogens, and the production of signal specific mediators to engage immune cells for clearance of infectious agents. Pathogen-specific signals establish basis for the initiation of adoptive immune responses. These immune regulatory roles of MCs have opened avenues to engage different MCs activators which culminate in effective passive immunisation. The molecular mechanisms and dynamics of functionalities of MCs in host defences have been extensively characterised in mammals and rodents, and research on MCs in avian species is emerging. This review surveys the development, morphology and distribution of MCs in different tissues of the poultry and highlight areas that can be exploited for disease control and prevention.

Dendritic cells (DCs) are antigen-presenting cells (APCs) with the unique ability to induce both innate immune responses and a highly specific acquired immunity. DCs are crucial to induce immunity, and their maturation and functions are influenced by microbial and environmental stimuli. Chicken DCs are composed of several subtypes including bursal secretory dendritic cells (BSDCs), follicular dendritic cells (FDCs), and thymic dendritic cells (TDCs). DC maturation depends on the nature of the perturbation and permits unique and efficient immune responses for each pathogen. DCs differentially recognise the viruses, bacteria, parasite and fungi and specifically regulate the immune response. Dendritic cells (DCs) are ‘nature's adjuvants’ and, as such represent an essential component of any vaccination strategy. The understanding of DC regulatory mechanisms opens a new horizon for the development of new vaccines and their targeting with the vaccination for elicitation of better immunity levels. The following review summarises the current state of knowledge of DCs and their specific functions during host pathogens interaction.

The liver is the ‘central laboratory’ of a chicken's body, responsible for sorting and transforming digested compounds as well as dealing with waste products. It is essential that this organ is kept in an excellent condition in order to maintain a healthy bird. Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families, including fowl adenoviruses (FAdV), avian hepatitis E virus (HEV), duck hepatitis virus (DHV), and turkey hepatitis virus (THV). Although, these viruses target the liver primarily, they each possess unique clinical and biological features. Hydropericardium syndrome (HPS) is a highly infectious disease caused by FAdV serotype 4 (FAdV-4) affecting poultry, especially broilers, and is characterised by the accumulation of fluid in the pericardial sac and hepatitis. Inclusion body hepatitis (IBH) was recognised firstly in the US, and the disease has now been reported in many countries. FAdV, the causative agent of inclusion body hepatitis, is a Group I avian adenovirus in the genus Aviadenovirus. The affected birds have a pale, swollen, friable, and haemorrhagic liver with pathognomonic histological lesions including intranuclear inclusion bodies in the nuclei of the hepatocytes. Avian HEV naturally infects chickens and is associated with hepatitis-splenomegaly syndrome, although the majority of the infected birds are subclinical. THV is a picornavirus that is likely the causative agent of turkey viral hepatitis. Currently there are more questions than answers about THV, and pathogenesis and clinical impact remains largely unknown. Future research into viral hepatic diseases of poultry is warranted to develop effective vaccines, specific diagnostic assays, and identify suitable cell culture systems for virus propagation. This review covers the common and unique features of major hepatitis causing viruses, with emphasis on FAdV, HEV and THV in an effort to identify the knowledge gaps and aid prevention and control of poultry viral hepatitis.

We, the Editor and Publisher of World’s Poultry Science Journal, have retracted the following article:M.T. Munir, Z.U. Rehman, M.A. Shah & S. Umar, ‘Interactions of Aspergillus fumigatus with the r...

The objective of the present study was to determine the effect of broiler breeder egg weight on egg quality, chick quality, and broiler performance using Hubbard Classic broiler breeder flock. Hatching eggs from a commercial broiler breeder flock (Hubbard classic strain) were obtained at the age of 60 wk and divided into 3 egg-weight categories, namely small, medium, and large. For this purpose, 930 eggs having weights 63.09 ± 0.21, 68.85 ± 0.23, and 74.81 ± 0.11g were divided into 3 egg categories labeled small, medium, and large respectively. We further divided these eggs into 2 categories, eggs for quality parameters and eggs for incubation and posthatch performance parameters. Eggs from the small egg category had greater proportion of the shell weight and more shell strength. Egg weight did not significantly affect the albumen and yolk weight percentage. Egg weight affected the shape index and specific gravity for which lower values were observed for large eggs. Egg weight positively affected the chick weight, chick yield, and chick length (P

The present study was designed to alleviate the negative biohazards of high ambient temperature on the productive performance and physiological status of laying hens. A total of 135 Bovans laying hens were distributed into nine groups in a 3 × 3 factorial design experiment. Basal diet was supplemented with vitamin E at levels of 0, 250, and 500 mg /kg diet. Within each dietary vitamin E level, each diet was supplemented with sodium selenite as a source of selenium (Se) to supply 0, 0.25, and 0.50 mg Se/kg diet. Results showed that supplementing layer's diet with 500 mg vitamin E/kg was accompanied with the lowest feed consumption (FC) and feed conversion ratio (FCR). The interaction among vitamin E and Se levels exerted significant effects only on FC and FCR. Insignificant differences were observed in egg quality criteria due to the treatments studied. Increasing vitamin E level was associated with a gradual decrease in basophil count and an increase in monocytes. A gradual decrease in the count of each of heterophils, monocytes, and eosinophils was observed with the elevation in the dietary Se level. The combination among vitamin E and Se levels produced a significant effect on all hematological parameters studied. As vitamin E increased, a marked decrease in serum AST and a gradual increase in total lipids, total cholesterol, and calcium were observed. As the level of dietary Se increased, serum total protein, albumin, T4, total cholesterol, and total lipids increased. No significant impacts were detected for the interaction among vitamin E and Se levels on any of blood constituents determined except serum globulin, ALT, and calcium. In conclusion, the combination between vitamin E and Se showed a good ability to alleviate the harmful impacts of heat stress and produced the highest productive performance when compared with the other groups, which exhibit the synergistic effect between the two antioxidants.

Immune dysfunction can be either at the humoral or cellular levels and is mediated by a myriad of factors including virus-induced immunosuppression. Infectious bursal disease virus (IBDV) affects domesticated poultry and causing health problems mainly due to prolonged immunosuppression. Destruction of the immunoglobulin-producing cells is the principal cause of IBDV-induced immunosuppression, which leads to significant impairment of the primary antibody responses. Due to these effects, IBDV infection not only increases the susceptibility of poultry to other viral infections but predisposes the host to several other bacteria of variable pathologies. The IBDV-induced immune-suppression is well-known phenomenon, however, recently there have been significant advancements in understanding the molecular mechanisms of this immune-suppression. This review discuss current updates regarding the immunotoxic and immunosuppressive nature of IBDV in the poultry and highlights areas requiring future research attentions that may help to establish foundations for effective and improved vaccines against IBDV.

Paramyxovirus establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Of the various pattern recognition receptors in the host, the cytosolic RNA helicases interact with viral RNA to activate the mitochondrial antiviral signaling protein (MAVS) and subsequent cellular interferon (IFN) response. On the other hand, viruses explore multiple strategies to resist host immunity. In this study, we found that Newcastle disease virus (NDV) infection induced MAVS degradation. Further analysis showed that NDV V protein degraded MAVS through the ubiquitin-proteasome pathway to inhibit IFN-β production. Moreover, NDV V protein led to proteasomal degradation of MAVS through Lys362 and Lys461 ubiquitin to prevent IFN production. Further studies showed that NDV V protein recruited E3 ubiquitin ligase RNF5 to polyubiquitinate and degrade MAVS. Compared with levels for wild-type NDV infection, V-deficient NDV induced attenuated MAVS degradation and enhanced IFN-β production at the late stage of infection. Several other paramyxovirus V proteins showed activities of degrading MAVS and blocking IFN production similar to those of NDV V protein. The present study revealed a novel role of NDV V protein in targeting MAVS to inhibit cellular IFN production, which reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit. IMPORTANCE Host anti-RNA virus innate immunity relies mainly on the recognition by retinoic acid-inducible gene I and melanoma differentiation-associated protein 5 and subsequently initiates downstream signaling through interaction with MAVS. On the other hand, viruses have developed various strategies to counteract MAVS-mediated signaling. The mechanism for paramyxoviruses regulating MAVS to benefit their infection remains unknown. In this article, we demonstrate that the V proteins of NDV and several other paramyxoviruses target MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase RING-finger protein 5 (RNF5). MAVS degradation leads to the inhibition of the downstream IFN-β pathway and therefore benefits virus proliferation. Our study reveals a novel mechanism of NDV evading host innate immunity and provides insight into the therapeutic strategies for the control of paramyxovirus infection.

International audience; AbstractThe fusogenically activated F and HN proteins of virulent NDV induce complete autophagic flux in DF-1 and A549 cells. However, the effect of both glycoproteins on mitochondria remains elusive. Here, we found that F and HN cooperation increases mitochondrial biogenesis but does not cause the mitochondria damage. We observed that both glycoproteins change the morphological characteristics and spatial distribution of intracellular mitochondria. F and HN cooperate cooperatively to induce ER stress and UPRmt. Our preliminary data suggested that F and HN cooperatively disturb mitochondrial fusion–fission homeostasis to enhance mitochondrial biogenesis, and eventually meet the energy demand of syncytium formation.

Deoxyribonucleic acid (DNA) damage response (DDR) is the fundamental cellular response for maintaining genomic integrity and suppressing tumorigenesis. The activation of ataxia telangiectasia-mutated (ATM) kinase is central to DNA double-strand break (DSB) for maintaining host-genome integrity in mammalian cells. Oncolytic Newcastle disease virus (NDV) can selectively replicate in tumor cells; however, its influence on the genome integrity of tumor cells is not well-elucidated. Here, we found that membrane fusion and NDV infection triggered DSBs in tumor cells. The late replication and membrane fusion of NDV mechanistically activated the ATM-mediated DSB pathway via the ATM-Chk2 axis, as evidenced by the hallmarks of DSBs, i.e., auto-phosphorylated ATM and phosphorylated H2AX and Chk2. Immunofluorescence data showed that multifaceted ATM-controlled phosphorylation markedly induced the formation of pan-nuclear punctum foci in response to NDV infection and F-HN co-expression. Specific drug-inhibitory experiments on ATM kinase activity further suggested that ATM-mediated DSBs facilitated NDV replication and membrane fusion. We confirmed that the Mre11-RAD50-NBS1 (MRN) complex sensed the DSB signal activation triggered by NDV infection and membrane fusion. The pharmacological inhibition of MRN activity also significantly inhibited intracellular and extracellular NDV replication and syncytia formation. Collectively, these data identified for the first time a direct link between the membrane fusion induced by virus infection and DDR pathways, thereby providing new insights into the efficient replication of oncolytic NDV in tumor cells., Author summary Various viruses have evolved a plethora of strategies to manipulate DNA damage machinery and commandeer cells to maximize their own replication. On the contrary, host cells have also evolved to maintain cellular genomic stability and suppress carcinogenesis through multifaceted cellular DNA damage response (DDR). Most studies have focused on the relationship between DNA virus replication and the host DDR pathway, but few have investigated the interface between the DDR pathway and ribonucleic acid (RNA) viruses, such as oncolytic Newcastle disease virus (NDV). In the present study, we report for the first time that F-HN co-expression and NDV infection trigger ataxia telangiectasia-mutated (ATM)-dependent DSB lesions in tumor cells to promote viral replication and syncytium formation, respectively. We found that late NDV infection and membrane fusion activated the ATM-Chk2 axis in tumor cells, which expands prior understanding of the membrane fusion process and NDV infection. Our findings reveal new links among oncolytic NDV replication, membrane fusion, and DDR and deepen insights into NDV replication.

International audience; AbstractAvian avulaviruses serotype 1 (abbreviated as APMV-1 for the historical name avian paramyxovirus 1) are capable of infecting a wide spectrum of avian species with variable clinical symptoms and outcomes. Ease of transmission has allowed the virus to spread worldwide with varying degrees of virulence depending upon the virus strain and host species. The emergence of new virulent genotypes from global epizootics, and the year-to-year genomic changes in low and high virulence APMV-1 imply that distinct genotypes of APMV-1 are simultaneously evolving at different geographic locations across the globe. This vast genomic diversity may be favoured by large variety of avian species susceptibility to APMV-1 infection, and by the availability of highly mobile wild birds. It has long been considered that waterfowls are not sensitive to APMV-1 and are unable to show any clinical signs, however, outbreaks from the 90′s contradict these concepts. The APMV-1 isolates are increasingly reported from the waterfowl. Waterfowl have strong innate immune responses, which minimize the impact of virus infection, however, are unable to prevent the viral shedding. Numerous APMV-1 are carried by domestic waterfowl intermingling with terrestrial poultry. Therefore, commercial ducks and geese should be vaccinated against APMV-1 to minimize the virus shedding and for the prevention the transmission. Genetic diversity within APMV-1 demonstrates the need for continual monitoring of viral evolution and periodic updates of vaccine seed-strains to achieve efficient control and eradication of APMV-1 in waterfowls.

Mitochondrial antiviral-signaling protein (MAVS) is an essential adaptor protein in retinoic acid-inducible gene I (RIG-I)-mediated antiviral innate immunity in mammals. In this study, the goose MAVS gene (goMAVS) was identified. The 2019 bp-long goMAVS exhibits 96.2% amino acid similarity compared to the predicted goMAVS. Quantitative real-time polymerase chain reactions showed that goMAVS mRNA was widely expressed in different tissues. The overexpression of goMAVS in goose embryo fibroblast cells up-regulated the mRNA levels of goose interferon-stimulated genes. We concluded that MAVS mediates the activation of type I interferon (IFN) pathway in a species-specific manner. We further demonstrated that a CARD-like domain, transmembrane domain and two previously unidentified domains of goMAVS were essential for the activation of type I IFN pathway. GoMAVS inhibited Newcastle disease virus replication by activating type I IFN pathways, especially at the early stages of infection. Finally, the interaction between goMAVS and goose RIG-I was confirmed. The CARD domain of goMAVS plays a vital role in the interaction. Together, we identified goMAVS as a goRIG-I interactive protein and concluded that goMAVS is involved in the activation of type I IFN pathways in goose cells.

A 3 × 2 factorial arrangement was implemented to determine the performance of 450 Cobb broilers subjected to different feeding regimes with and without lighting programs. The chicks were divided into 3 groups according to the feeding regime (ad libitum, restricted, or intermittent), and each group was reared under one of two lighting programs (100% continuous light or 50% continuous light and 50% flashing light). The results showed that the broilers under the ad libitum and intermittent feeding regimes had superior body weight (BW) and average daily gain (ADG) values and the lowest feed conversion ratio (FCR) at 3 and 6 wk of age. Broilers exposed to flashing light and an intermittent feeding regime had the highest BW and ADG values and the lowest FCR. Birds exposed to intermittent feeding had the highest dressed carcass weight and the lowest heart weight. Broilers reared with flashing light had higher tenderness and juiciness values than the other groups. Broilers subjected to a restricted feeding regime and flashing light had the lowest abdominal fat values of all the groups. Tenderness and juiciness were significantly higher in broilers subjected to the ad libitum feeding regime × flashing light and the intermittent feeding regime × flashing light. Broilers fed an intermittent regime had the lowest spleen %, heterophil, heterophil to lymphocyte (H/L) ratio and body temperature values of all the groups, and broilers reared under the intermittent regime × flashing light had the lowest spleen %, H/L ratio and body temperature values. Non-significant differences in all health aspects (shank length, keel bone length, foot pad burns, breast blisters score, hock discoloration, and mortality) were observed among the experimental groups. In conclusion, intermittent and restricted feeding regimes and a flashing lighting program improved the FCR and did not produce any adverse effects on performance or physiological parameters. The results of this work show that intermittent feeding and flashing lighting programs are more beneficial to broiler management.

Newcastle disease (ND), caused by ND virus (NDV), is one of the most infectious and economically important diseases of the poultry industry worldwide. While infections are reported in a wide range of avian species, the pathogenicity of chicken-origin virulent NDV isolates in ducks remains elusive. In this study, two NDV strains were isolated and biologically and genetically characterized from an outbreak in chickens and apparently healthy ducks. Pathogenicity assessment indices, including the mean death time (MDT), intracerebral pathogenicity index (ICPI) and cleavage motifs in the fusion (F) protein, indicated that both isolates were velogenic in nature. While these isolates carried pathogenic characteristics, interestingly they showed differential pathogenicity in ducks. The chicken-origin isolate caused high (70%) mortality, whereas the duck-origin virus resulted in low (20%) mortality in 4-week-old ducks. Intriguingly, both isolates showed comparable disease pathologies in chickens. Full-genome sequence analysis showed that the virus genome contains 15 192 nucleotides and carried features that are characteristic of velogenic strains of NDV. A phylogenetic analysis revealed that both isolates clustered in class II and genotype VII. However, there were several mutations in the functionally important regions of the fusion (F) and haemagglutinin-neuraminidase (HN) proteins, which may be responsible for the differential pathogenicity of these viruses in ducks. In summary, these results suggest that NDV strains with the same genotype show differential pathogenicity in chickens and ducks. Furthermore, chicken-origin virulent NDVs are more pathogenic for ducks than duck-origin viruses. These findings propose a role for chickens in the evolution of viral pathogenicity and the potential genetic resistance of ducks to poultry viruses.

Newcastle disease (ND), characterized by visceral, respiratory, and neurological pathologies, causes heavy economic loss in the poultry industry around the globe. While significant advances have been made in effective diagnosis and vaccine development, molecular mechanisms of ND virus (NDV)-induced neuropathologies remain elusive. In this study, we report the magnitude of oxidative stress and histopathological changes induced by the virulent NDV (ZJ1 strain) and assess the impact of vitamin E in alleviating these pathologies. Comparative profiling of plasma and brains from mock and NDV-infected chicken demonstrated alterations in several oxidative stress makers such as nitric oxide, glutathione, malondialdehyde, total antioxidant capacity, glutathione S-transferase, superoxide dismutase, and catalases. While decreased levels of glutathione and total antioxidant capacity and increased concentrations of malondialdehyde and nitric oxide were observed in NDV-challenged birds at all time points, these alterations were eminent at latter time points (5 days post infection). Additionally, significant decreases in the activities of glutathione S-transferase, superoxide dismutase, and catalase were observed in the plasma and brains collected from NDV-infected chickens. Intriguingly, we observed that supplementation of vitamin E can significantly reduce the alteration of oxidative stress parameters. Under NDV infection, extensive histopathological alterations were observed in chicken brain including neural inflammation, capillary hyperemia, necrosis, and loss of prominent axons, which were reduced with the treatment of vitamin E. Taken together, our findings highlight that neurotropic NDV induces extensive tissue damage in the brain and alters plasma oxidative stress profiles. These findings also demonstrate that supplementing vitamin E ameliorates these pathologies in chickens and proposes its supplementation for NDV-induced stresses.

Reactive species (RS), generally known as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are produced during regular metabolism in the host and are required for many cellular processes such as cytokine transcription, immunomodulation, ion transport, and apoptosis. Intriguingly, both RNS and ROS are commonly triggered by the pathogenic viruses and are famous for their dual roles in the clearance of viruses and pathological implications. Uncontrolled production of reactive species results in oxidative stress and causes damage in proteins, lipids, DNA, and cellular structures. In this review, we describe the production of RS, their detoxification by a cellular antioxidant system, and how these RS damage the proteins, lipids, and DNA. Given the widespread importance of RS in avian viral diseases, oxidative stress pathways are of utmost importance for targeted therapeutics. Therefore, a special focus is provided on avian virus-mediated oxidative stresses. Finally, future research perspectives are discussed on the exploitation of these pathways to treat viral diseases of poultry.

Background/Aims: Newcastle disease virus (NDV) causes a highly devastating and contagious disease in poultry, which is mainly attributed to extensive tissue damages in the digestive, respiratory and nervous systems. However, nature and dynamics of NDV-induced oxidative stresses in the intestine of chickens remain elusive. Methods: In this study, we examined the magnitude of intestinal oxidative stress and histopathological changes caused by the virulent NDV infection, and explored the protective roles of vitamin E (vit. E) in ameliorating these pathological changes. For these purposes, chickens were divided into four groups namely i) non supplemented and non-challenged (negative control, CON); ii) no supplementation of vit. E but challenged with ZJ1 (positive control, NS+CHA); iii) vit. E supplementation at the dose of 50 IU/day/Kg body weight and ZJ1 challenge (VE50+CHA); and 4) vit. E supplementation at the dose of 100 IU/day/Kg body weight and ZJ1 challenge (VE100+CHA). In all groups, we analyzed concentrations of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T-AOC), and activity of glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) using biochemical methods. The virus loads were determined by quantitative RT-PCR and antibody titers by hemagglutination inhibition assays. We also examined the histopathological changes in the duodenal and jejunal mucosa at 3 and 5-day post infection (dpi) with NDV. Results: A significant elevation in the NO level was observed in NDV challenged chickens compared to the CON chickens at 2 dpi. The MDA contents were significantly increased whereas GSH was significantly decreased in NDV-challenged chickens compared to control. Furthermore, activities of GST, CAT, SOD, as well as the TOAC were markedly decreased in challenged chickens in comparison with control. Virus copy numbers were higher in NDV infected NS+CHA group compared to other groups. Severe histopathological changes including inflammation, degeneration and broken villi were observed in the intestine of NDV challenged chickens. However, all these malfunctions of antioxidant system and pathological changes in the intestine were partially or completely reversed by the vit. E supplementation. Conclusions: Our results suggest that NDV infection causes oxidative stress and histopathological changes in the duodenum and jejunum of chickens, which can be partially or fully ameliorated by supplementation of vit. E. Additionally, these findings suggest that oxidative stress contributes to the intestinal damages in NDV infected chickens. These findings will help to understand the pathogenesis of NDV and further investigation of therapeutic agents for control of Newcastle disease.

Rapeseed meal (RSM) is a commonly used protein source in poultry diet but its usage is limited due to antinutritional factors, the glucosinolates (GLS) and erucic acid. The 00-rapeseed meal (00-RSM) is the developed variety of rapeseed with reduced GLS and erucic acid content through genetic selection. The present study was conducted with the objective of comparing the standardized ileal digestibility (SID) of amino acids (AA) in 00-RSM and RSM when fed to growing broilers. Three samples of each ingredient were collected from different sources. Two hundred and fifty two day-old male broilers (Hubbard × Hubbard) were fed a corn-soybean meal based starter diet in crumble form from day 1 to 13. On day 14, all chicks were individually weighed and randomly distributed to 42 replicate pens (6 birds in each pen). Six test diets (2 ingredient × 3 samples) with approximately 20% crude protein were made in mash form in such a way that the 6 test ingredients served as the sole source of AA in one diet. The endogenous AAs (EAA) were determined by feeding a nitrogen-free diet to six replicate pens. Each test diet was fed to six replicates of broiler chicks from 14 to 21 days of age. Results indicated that the SID of all AA differed (P 0.001) among 00-RSM samples. Among RSM samples, the SID of AA varied for arginine, methionine (P 0.01), histidine, leucine, lysine, aspartic acid, and phenylalanine (P 0.05). A greater (P 0.05) SID of all AA except arginine, histidine, phenylalanine, cysteine, and glutamic acid was observed in 00-RSM compared with RSM. In conclusion, 00-RSM had greater SID of AA compared with RSM and it is nutritionally superior to RSM to be used in broiler diets.

A 42-day experiment was conducted with 625 1-day-old male Hubbard chickens to evaluate the performance, carcass traits, nitrogen retention and economics of broiler chickens fed low protein and amino acid diets supplemented with different protease sources. Treatments included positive (PC) and negative (NC) controls (PC at 19.3% protein vs NC at 18.8% protein), with NC containing 7% less digestible amino acids. The other three treatment groups were based on the NC diet supplemented with 0.05% Cibenza® DP100 (CB), 0.02% Ronozyme® (RZ) or 0.02% Winzyme pro plus (WZ). Birds fed the PC, CB and WZ diets achieved the heaviest bodyweight compared with those fed the NC diet at end of the experiment. Total feed intake of birds fed the PC diet was higher (P < 0.05) than that of birds fed the NC diet. Feed conversion ratio was numerically significantly (P = 0.005) improved with all tested groups in comparison with NC throughout the experiment. European production index was similar (P > 0.05) among birds fed the PC, NC, RZ or WZ diets. All carcass parameters studied, including dressing, heart, gizzard, giblets, chest meat, thigh meat and abdominal fat percentages, were not significantly (P > 0.05) affected by feeding on the different sources of protease. Broilers fed the PC diet or diets formulated with all protease sources had higher (P < 0.05) nitrogen retention than did birds fed the NC diet. The supplementation of protease to low-protein and low-amino acid diets resulted in higher profit margin in broilers. It is concluded that supplementing exogenous protease to broiler diets containing low protein and amino acids improved the growth performance, feed utilisation, carcass traits, nitrogen retention and net returns of broiler chickens.

The main objective of this study was to determine the possible effects of Nigella sativa on immune-response and pathogenesis of H9N2 avian influenza virus in turkeys. The experiment was performed on 130 non-vaccinated mixed-sex turkey poults, divided into five experimental groups of 30 birds each. Group A was kept as non-infected and a non-treated negative control while group B was kept as infected and non-treated positive control. Turkeys in groups A and B received normal commercial feed while turkeys of groups C, D and E were fed on diets containing 2%, 4% and 4% NS seeds, respectively, from day one through the entire experiment period. All groups were challenged with H9N2 AIV at 4th week of age except group A. Infected turkeys showed clinical signs of different severity, showing the most prominent disease signs in turkeys of the group B. All infected turkeys showed positive results for virus shedding; however, the pattern of virus shedding was different, and with turkeys of the group B showing pronounced virus secretion than the turkeys in other groups receiving different levels of NS. Moreover, significantly higher antibody titer against H9N2 AIV in turkeys fed 6% NS seeds shows the immunomodulatory nature of NS. Similarly, increased cytokine gene expression suggests antiviral behavior of NS especially in dose dependent manner, leading to suppressed pathogenesis of H9N2 viruses. However, reduced virus shedding and enhanced immune responses were more pronounced in those turkeys received NS at the rate of 4% and 6%. This study showed that supplement of NS would significantly enhance immune responsiveness and suppress pathogenicity of influenza viruses in turkeys.