scholarly journals Fiber-1, Not Fiber-2, Directly Mediates the Infection of the Pathogenic Serotype 4 Fowl Adenovirus via Its Shaft and Knob Domains

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Weikang Wang ◽  
Qian Liu ◽  
Tuofan Li ◽  
Tuoyu Geng ◽  
Hongjun Chen ◽  
...  
Keyword(s):  
Surface Proteins ◽  
Economic Losses ◽  
Exact Role ◽  
Lethal Challenge ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Key Factor ◽  
Efficient Protection ◽  
Viral Surface

ABSTRACT Recently, the disease of hepatitis-hydropericardium syndrome (HPS) caused by serotype 4 fowl adenovirus (FAdV-4) has spread widely and resulted in huge economic losses to the poultry industry. Although the genome of FAdV-4 has two fiber genes (fiber-1 and fiber-2), the exact role of the genes in the infection of FAdV-4 is barely known. In this study, through superinfection resistance analysis and an interfering assay, we found that fiber-1, but not fiber-2, was the key factor for directly triggering the infection of FAdV-4. The truncation analysis further revealed that both of the shaft and knob domains of fiber-1 were required for the infection. Moreover, the sera against the knob domain were able to block FAdV-4 infection, and the knob-containing fusion protein provided efficient protection against the lethal challenge of FAdV-4 in chickens. All the data demonstrated the significant roles of fiber-1 and its knob domain in directly mediating the infection of FAdV-4, which established a foundation for identifying the receptor of FAdV-4 and developing efficient vaccines against FAdV-4. IMPORTANCE Among 12 serotypes of fowl adenovirus (FAdV), FAdV-1, FAdV-4, and FAdV-10 all carry two fiber genes (i.e., fiber-1 and fiber-2), whereas other serotypes have only one. As important viral surface proteins, the fibers play vital roles in the infection and pathogenesis of FAdV. However, the importance of the fibers to the infection and pathogenesis of FAdV may be different from each other. Recent studies reveal that fiber-2 is identified as a determinant of virulence, but which fiber triggers the infection of FAdV-4 remains unknown. In this study, fiber-1 was identified as a key factor for directly mediating the infection of FAdV-4 through its shaft and knob domains, whereas fiber-2 did not play a role in triggering FAdV-4 infection. The results suggest that fiber-1 and its knob domain may serve as a target for identifying the receptor of FAdV-4 and developing efficient drugs or vaccines against FAdV-4.

scholarly journals A Novel Fiber-1-Edited and Highly Attenuated Recombinant Serotype 4 Fowl Adenovirus Confers Efficient Protection Against Lethal Challenge

2021 ◽  
Vol 8 ◽  
Author(s):  
Yaru Mu ◽  
Quan Xie ◽  
Weikang Wang ◽  
Hao Lu ◽  
Mingjun Lian ◽  
...  
Keyword(s):  
Recombinant Virus ◽  
Animal Studies ◽  
Insertion Site ◽  
Economic Losses ◽  
Lethal Challenge ◽  
Live Attenuated Vaccine ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Efficient Protection

Currently, a fatal disease of hepatitis-hydropericardium syndrome (HHS) caused by serotype 4 fowl adenovirus (FAdV-4) has spread worldwide and resulted in tremendous economic losses to the poultry industry. Various vaccines against FAdV-4 were developed to control the disease; however, few live-attenuated vaccines were available. In this study, we targeted the N-terminal of fiber-1 and rescued a recombinant virus FAdV4-RFP_F1 expressing the fusion protein of RFP and Fiber-1 based on the CRISPR/Cas9 technique. In vitro studies showed that FAdV4-RFP_F1 replicated slower than the wild type FAdV-4, but the peak viral titer of FAdV4-RFP_F1 could still reach 107.0 TCID50/ml with high stability in LMH cells. Animal studies found that FAdV4-RFP_F1 not only was highly attenuated to the 2-week-old SPF chickens, but could also provide efficient protection against lethal challenge of FAdV-4. All these demonstrate that the recombinant virus FAdV4-RFP_F1 could be as an efficient live-attenuated vaccine candidate for FAdV-4, and the N-terminal of fiber-1 could be as a potential insertion site for expressing foreign genes to develop FAdV-4-based vaccine.

scholarly journals Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Pan ◽  
Yu Zhang ◽  
Aijing Liu ◽  
Hongyu Cui ◽  
Yulong Gao ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Virus Genome ◽  
Open Reading Frames ◽  
Vaccine Vector ◽  
Economic Losses ◽  
Foreign Gene ◽  
The Novel ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Green Fluorescent

Severe hepatitis-hydropericardium syndrome (HHS) associated with a novel viral genotype, fowl adenovirus 4 (FAdV-4), has emerged and widely spread in China since 2015, causing severe economic losses to the poultry industry. We previously reported that the hexon gene is responsible for pathogenicity and obtained a non-pathogenic hexon-replacement rHN20 strain; however, the lack of information about the non-essential regions for virus replication limits the development of a FAdV-4 vector. This study first established an enhanced green fluorescent protein (EGFP)-indicator virus based on the FAdV-4 reverse genetic technique, effective for batch operations in the virus genome. Based on this, 10 open reading frames (ORFs) at the left end and 13 ORFs at the right end of the novel FAdV-4 genome were deleted separately and identified as non-essential genes for viral replication, providing preliminary insertion sites for foreign genes. To further improve its feasibility as a vaccine vector, seven combinations of ORFs were successfully replaced with EGFP without affecting the immunogenicity of the vector backbone. Finally, a recombinant rHN20-vvIBDV-VP2 strain, expressing the VP2 protein of very virulent infectious bursa disease virus (vvIBDV), was rescued and showed complete protection against FAdV-4 and vvIBDV. Thus, the novel FAdV-4 vector could provide sufficient protection for HHS and efficient exogenous gene delivery. Overall, our findings systemically identified 23 non-essential ORFs for FAdV-4 replication and seven foreign gene insertion regions, providing valuable information for an in-depth understanding of the novel FAdV-4 pathogenesis and development of multivalent vaccines.

scholarly journals Airborne Transmission of a Serotype 4 Fowl Adenovirus in Chickens

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 262 ◽  
Author(s):  
Gang Li ◽  
Guanliu Yu ◽  
Yujuan Niu ◽  
Yumei Cai ◽  
Sidang Liu
Keyword(s):  
Infectious Disease ◽  
Infected Group ◽  
Economic Losses ◽  
Control Group ◽  
Airborne Transmission ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Viral Aerosol ◽  
Subclinical Symptoms ◽  
And Control

Serotype 4 fowl adenovirus (FAdV-4) is the main pathogen for hydropericardium syndrome (HPS) in chickens. It has caused major economic losses in the global poultry industry. Currently, FAdV-4′s transmission routes in chickens remain unclear. Here we investigate the airborne transmission routes of FAdV-4 in chickens. A total of 45 ten-day-old chickens were equally divided into three groups (infected group/isolator A, airborne group/isolator B, and control group/isolator C). Of note, isolators A and B were connected by a leak-free pipe. The results showed that the virus could form a viral aerosol, detected in isolators two days post infection (dpi). The viral aerosol reached a peak at 4 dpi in the infected group. Healthy chickens in the airborne group were infected by the virus at 8 dpi. The chickens of the airborne group demonstrated subclinical symptoms capable of shedding the virus for some time. This finding suggests that FAdV-4 can be efficiently transmitted among chickens by aerosol transmission. These findings have significant implications for developing strategies to control this infectious disease epidemic.

Stimulierung der Immunreaktivität gegen endogene Retroviren und Schutz gegen Leukämie bei älteren AKR-Mäusen nach Impfung mit Antikörpern gegen Virusoberflächen-Komponenten. Rolle des Antikörpers gegen p15(E) / Stimulation of Immunoreactivity against Endogenous Retroviruses and Protection against Leukem ia of Older AKR Mice by Treatment with Antibodies against Retroviral Surface Components. Role of p15 (E) Antibody

1984 ◽  
Vol 39 (11-12) ◽  
pp. 1199-1202 ◽  
Author(s):  
Heinz Schwarz ◽  
H.-J. Thiel ◽  
Kent J. Weinhold ◽  
Dani P. Bolognesi ◽  
Werner Schäfer
Keyword(s):  
Endogenous Retroviruses ◽  
Surface Proteins ◽  
Endogenous Virus ◽  
Antibody Treatment ◽  
Immunodeficiency Syndrome ◽  
Akr Mice ◽  
Viral Surface ◽  
Stimulation Of

Abstract Antibody against viral gp71 is effective therapeutically for high leukemic AKR mice if injected immediately after birth [1], No corresponding effect could be observed after inoculation later in life when the endogenous virus burden is already high. However, if antibody treatment was supplemented by the injection of pi5(E) antibody, a thera­peutic effect was observed even in older mice first treated at an age of 21/2 months. Those mice produced antibodies against viral surface proteins and appeared to be able to survive longer than control mice. Thus pi5(E) antibody might be able to overcome retroviral associated immuno­deficiency. This therapy may have implications for the treatment of the apparently retroviral induced aquired immunodeficiency syndrome (AIDS) of man.

scholarly journals Requirement of Cellular Protein CCT7 for the Replication of Fowl Adenovirus Serotype 4 (FAdV-4) in Leghorn Male Hepatocellular Cells Via Interaction with the Viral Hexon Protein

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 107 ◽  
Author(s):  
Junfeng Gao ◽  
Mingliang Zhao ◽  
Xueyan Duan ◽  
Yongqiang Wang ◽  
Hong Cao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Cellular Protein ◽  
Economic Losses ◽  
Adenovirus Serotype ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Infected Cells ◽  
Lmh Cells ◽  
Fowl Adenovirus Serotype 4

Fowl adenovirus serotype 4 (FAdV-4) causes hepatitis-hydropericardium syndrome (HHS), leading to severe economic losses in the poultry industry. Although the pathogenesis of FAdV-4 infection has caused much attention, the underlying molecular mechanisms remain poorly understood. Here, we identified chaperonin containing TCP-1 subunit eta (CCT7) as an interacting partner of the FAdV-4 capsid protein hexon. We found that ectopic expression of CCT7 in leghorn male hepatocellular (LMH) cells enhanced hexon expression in pRK5-flag-hexon transfected cells. On the contrary, knockdown of cellular CCT7 by RNAi markedly reduced hexon expression in FAdV-4-infected cells and suppressed viral replication. These data suggest that CCT7 is required for FAdV-4 replication and may serve as a potential target for controlling FAdV-4 infection.

scholarly journals Identification of novel B cell epitopes in the fiber protein of serotype 8 Fowl adenovirus

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hao Lu ◽  
Hongxia Shao ◽  
Hongjun Chen ◽  
Jianjun Zhang ◽  
Weikang Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Epitope ◽  
Economic Losses ◽  
The Novel ◽  
B Cell Epitopes ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Fiber Protein ◽  
Inclusion Body Hepatitis ◽  
B Cell Epitope

Abstract In recent years, hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH) caused by fowl adenovirus (FAdV) infection have resulted in significant economic losses to the poultry industry worldwide. Epidemiological analysis revealed that serotype FAdV-8 is one of the major pathogenic FAdVs currently prevalent in domestic flocks. Although the fiber protein of FAdV plays vital roles in viral infection and pathogenesis, the B cell epitope in the fiber protein is less known. In this study, two monoclonal antibodies (mAbs) specific to fiber protein of FAdV-8, designated as 4D9 and 5F10, were prepared. Although the mAb 4D9 and 5F10 could not neutralize FAdV-8 infection, 4D9 and 5F10 showed good activities of indirect immunofluorescence, western blot and immunoprecipitation. Epitope analysis revealed that mAb 5F10 recognized 187–219aa in the fiber whereas mAb 4D9 recognized 113–149aa in the fiber. Sequence analysis showed that the epitope recognized by mAb 5F10 was conserve across serotypes FAdV-7, 8a and 8b whereas that for mAb 4D9 was only conserve in FAdV-8b. The generation of mAbs specific to fiber of FAdV-8 and the identification of the novel B cell epitopes here lay the foundation for further studying the antigenicity of the fiber and developing specific diagnosis for FAdV-8.

An efficient peptide-based ELISA for differentiating fowl adenovirus 4–infected chickens from vaccinated chickens

2021 ◽  
pp. 104063872110057
Author(s):  
Songhua Xie ◽  
Qiuping Shen ◽  
Wei Zhang ◽  
Weikang Wang ◽  
Quan Xie ◽  
...  
Keyword(s):  
Indirect Elisa ◽  
Nonstructural Protein ◽  
Immunofluorescence Assay ◽  
Economic Losses ◽  
Clinical Samples ◽  
Immunogenic Peptide ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Inactivated Vaccines ◽  
Fowl Adenovirus Serotype 4

Fowl adenovirus serotype 4 (FAdV4), the causative agent of hepatitis-hydropericardium syndrome (HPS), has caused major economic losses to the poultry industry worldwide. Although inactivated vaccines have been deployed widely against FAdV4, a DIVA (differentiating infected from vaccinated animals) test specific for FAdV4 has not been available. We synthesized an immunogenic peptide, corresponding to regions 66–88 aa of the 22K nonstructural protein of FAdV4, and used the peptide as coating antigen to develop an indirect ELISA for a DIVA test specific to FAdV4. Specificity analysis showed that the ELISA only reacted with sera against FAdV4, and not with sera against other pathogens tested. Moreover, the ELISA could effectively differentiate FAdV4–infected chickens from vaccinated chickens. In a test of sera from experimentally infected chickens, the ELISA had 95% and 85% concordance with an indirect immunofluorescence assay (indirect IFA) and a commercial ELISA, respectively, and the concordance was 80.5% between the ELISA and the indirect IFA in detecting clinical infection samples. Our peptide-based ELISA provides an efficient DIVA test for FAdV4 in clinical samples.

scholarly journals A novel fiber-2-edited live attenuated vaccine candidate against the highly pathogenic serotype 4 fowl adenovirus

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Quan Xie ◽  
Shiya Cao ◽  
Wei Zhang ◽  
Weikang Wang ◽  
Luyuan Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Insertion Site ◽  
Clinical Signs ◽  
Economic Losses ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Fowl Adenovirus

AbstractRecently, the outbreaks of hydropericardium-hepatitis syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry globally. Although several inactivated or subunit vaccines have been developed against FAdV-4, live-attenuated vaccines for FAdV-4 are rarely reported. In this study, a recombinant virus FA4-EGFP expressing EGFP-Fiber-2 fusion protein was generated by the CRISPR/Cas9 technique. Although FA4-EGFP shows slightly lower replication ability than the wild type (WT) FAdV-4, FA4-EGFP was significantly attenuated in vivo compared with the WT FAdV-4. Chickens infected with FA4-EGFP did not show any clinical signs, and all survived to 14 day post-infection (dpi), whereas those infected with FAdV-4 showed severe clinical signs with HHS and all died at 4 dpi. Besides, the inoculation of FA4-EGFP in chickens provided efficient protection against lethal challenge with FAdV-4. Compared with an inactivated vaccine, FA4-EGFP induced neutralizing antibodies with higher titers earlier. All these data not only provide a live-attenuated vaccine candidate against the highly pathogenic FAdV-4 but also give a potential insertion site for developing FAdV-4-based vaccine vectors for delivering foreign antigens.

scholarly journals Systematic Review on Mentalization as Key Factor in Psychotherapy

2021 ◽  
Vol 18 (17) ◽  
pp. 9161
Author(s):  
Jonas Lüdemann ◽  
Sven Rabung ◽  
Sylke Andreas
Keyword(s):  
Systematic Review ◽  
Psychotherapy Research ◽  
Exact Role ◽  
Key Factor ◽  
Electronic Database Search ◽  
Study Designs ◽  
The Impact ◽  
Present Systematic Review ◽  
Final Synthesis

Background: Mentalization processes seem to be of high relevance for social learning and seem important in all psychotherapies. The exact role of mentalization processes in psychotherapy is still unknown. The aim of the present systematic review is to investigate whether mentalization is related to the therapeutic outcome and, if so, whether it has a moderating, mediative, or predictive function. Method: A systematic review with an electronic database search was conducted. A total of 2567 records were identified, and 10 studies were included in the final synthesis. Results: Psychotherapy research is still in an initial phase of examining and understanding the impact of mentalization on psychotherapy outcome. The small number of studies and the executed study designs and statistical analyses indicate the possible role that mentalization has in psychotherapy. Conclusion: Generally, strongly elaborated study designs are needed to identify the role of mentalization in psychotherapy. Mentalization seems to be differently represented in differential treatment approaches. Nevertheless, it should be noted that the patient’s mentalizing capacity seems to be relevant to the psychotherapy process. Psychotherapies should be adapted to this.

scholarly journals NC2 complex is a key factor for the activation of catalase-3 transcription by regulating H2A.Z deposition

2020 ◽  
Vol 48 (15) ◽  
pp. 8332-8348
Author(s):  
Guofei Cui ◽  
Qing Dong ◽  
Jiabin Duan ◽  
Chengcheng Zhang ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Negative Regulator ◽  
Exact Role ◽  
Histone Fold ◽  
Chromatin Remodeling Complex ◽  
Key Factor ◽  
Repression Domain

Abstract Negative cofactor 2 (NC2), including two subunits NC2α and NC2β, is a conserved positive/negative regulator of class II gene transcription in eukaryotes. It is known that NC2 functions by regulating the assembly of the transcription preinitiation complex. However, the exact role of NC2 in transcriptional regulation is still unclear. Here, we reveal that, in Neurospora crassa, NC2 activates catalase-3 (cat-3) gene transcription in the form of heterodimer mediated by histone fold (HF) domains of two subunits. Deletion of HF domain in either of two subunits disrupts the NC2α–NC2β interaction and the binding of intact NC2 heterodimer to cat-3 locus. Loss of NC2 dramatically increases histone variant H2A.Z deposition at cat-3 locus. Further studies show that NC2 recruits chromatin remodeling complex INO80C to remove H2A.Z from the nucleosomes around cat-3 locus, resulting in transcriptional activation of cat-3. Besides HF domains of two subunits, interestingly, C-terminal repression domain of NC2β is required not only for NC2 binding to cat-3 locus, but also for the recruitment of INO80C to cat-3 locus and removal of H2A.Z from the nucleosomes. Collectively, our findings reveal a novel mechanism of NC2 in transcription activation through recruiting INO80C to remove H2A.Z from special H2A.Z-containing nucleosomes.

Sign in / Sign up

Export Citation Format

Share Document