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Journal of Virology Nov 2023The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases...
The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases immunosuppression and pathogenicity, extends the tumor spectrum, and accelerates viral evolution, causing substantial economic losses to the poultry industry. However, the mechanism of synergistic replication between ALV-J and REV is still incompletely elusive. We observed that microRNA-155 targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, interacting with the U3 region of ALV-J and REV, enabling synergistic replication. This work gives us new targets to modulate ALV-J and REV's synergistic replication, guiding future research on the mechanism.
Topics: Animals; Reticuloendotheliosis virus; Avian Leukosis; Avian Leukosis Virus; Chickens; Poultry Diseases; MicroRNAs; Virus Replication
PubMed: 37909729
DOI: 10.1128/jvi.00937-23 -
Avian Diseases Jun 2022Lymphoproliferative disease virus (LPDV) is an exogenous that sporadically causes fatal lymphoid neoplasia in affected turkeys. Previous studies of wild turkeys () in...
Lymphoproliferative disease virus (LPDV) is an exogenous that sporadically causes fatal lymphoid neoplasia in affected turkeys. Previous studies of wild turkeys () in the United States have demonstrated geographically widespread LPDV infection and frequent coinfection with avian poxvirus (APV) and reticuloendotheliosis virus (REV). This study was conducted to better understand health risks to Mississippi wild turkeys, including the relative importance of LPDV, APV, and REV in contributing to mortality. Thirteen wild turkeys, which died naturally or were euthanized due to illness, were submitted to Mississippi State University's Poultry Research and Diagnostic Laboratory for postmortem examinations. Birds originated from nine counties across the state over the past 5 yr. Carcasses were submitted as fresh (nonfrozen) or frozen. At autopsy, 9 of 13 turkeys had severe, proliferative cutaneous lesions on the head and neck, with diphtheritic or proliferative oral and esophageal lesions. Samples were collected for molecular diagnostic testing (LPDV and REV PCR), histopathology, and bacterial culture and isolation. External and internal parasites were preserved in formalin for identification. APV (cutaneous and/or diphtheritic forms) was diagnosed in 9 of 13 birds by identification of pathognomonic histologic lesions (including intracytoplasmic inclusion bodies). Interestingly, all birds with APV were also REV PCR positive. Furthermore, eight turkeys were positive for LPDV, and LPDV was commonly associated with coinfections with APV and REV.
Topics: Animals; Turkeys; Mississippi; Alpharetrovirus; Poxviridae; Poultry Diseases
PubMed: 35838749
DOI: 10.1637/aviandiseases-D-22-00007 -
Viruses Dec 2014Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However,... (Review)
Review
Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally discovered as cancer-causing agents, have a more random and potentially safer integration pattern compared to gammaretro- and lentiviruses. In this review, we provide a short overview of the history of alpharetroviruses and explain how they can be converted into state-of-the-art gene delivery tools with improved safety features. We discuss development of alpharetroviral vectors in compliance with regulatory requirements for clinical translation, and provide an outlook on possible future gene therapy applications. Taken together, this review is a broad overview of alpharetroviral vectors spanning the bridge from their parental virus discovery to their potential applicability in clinical settings.
Topics: Alpharetrovirus; Animals; Genetic Therapy; Genetic Vectors; Humans; Neoplasms; Virus Integration
PubMed: 25490763
DOI: 10.3390/v6124811 -
Avian Pathology : Journal of the W.V.P.A Apr 2022The laying hen has been used as a model for ovarian adenocarcinoma (OAC) in women. Previous work has shown an association between expression of endogenous retroviral...
The laying hen has been used as a model for ovarian adenocarcinoma (OAC) in women. Previous work has shown an association between expression of endogenous retroviral proteins and elevated envelope mRNA and occurrence of OAC in humans, but causality has not been demonstrated. The objective of this study was to determine whether there is a similar association between retrovirus presence and OAC in a commercial laying hen flock at the University of Illinois Poultry Research facility with a history of a high OAC prevalence in older hens. Laying hens of three age strata were randomly selected for a cross-sectional study. Blood samples were collected, and serum was tested for antigens of endogenous or exogenous avian leukosis virus (ALV) by ELISA. Birds were humanely euthanized, and spleens, ovaries, and any tissues with gross lesions were sampled. Ovaries and gross lesions were examined histologically and spleens were used for RT-PCR to detect endogenous ALV via ALV-E env mRNA expression. Overall, hens with OAC were 5.2 times more likely to be ALV positive than hens without OAC (95% C.I. 2.06-13.14). Controlled for age, OAC positive hens were 3.6 times more likely to be positive for ALV via antigen-capture ELISA (95% C.I. 1.08-11.96). Endogenous ALV-E in hens may be analogous to human endogenous retroviruses, which have also been associated with OAC in women. Further studies to establish causation are warranted to better understand the potential for laying hens to serve as a laboratory model for viral-induced ovarian tumours in humans. RESEARCH HIGHLIGHTSOAC in hens was associated with age, seropositivity for ALV, and endogenous ALV mRNA expression.Older hens with OAC were more likely to be ALV seropositive by ELISA and ALV-E mRNA-positive.Associations between OAC, age, and endogenous retrovirus expression have been reported in humans.These findings support the use of hens as models for OAC in humans.
Topics: Adenocarcinoma; Animals; Avian Leukosis; Avian Leukosis Virus; Chickens; Cross-Sectional Studies; Female; Poultry Diseases
PubMed: 34807789
DOI: 10.1080/03079457.2021.2007849 -
Journal of Virology Aug 2023Avian leukemia virus subgroup J (ALV-J) causes various diseases associated with tumor formation and decreased fertility and induced immunosuppressive disease, resulting...
Avian leukemia virus subgroup J (ALV-J) causes various diseases associated with tumor formation and decreased fertility and induced immunosuppressive disease, resulting in significant economic losses in the poultry industry globally. Virus usually exploits the host cellular machinery for their replication. Although there are increasing evidences for the cellular proteins involving viral replication, the interaction between ALV-J and host proteins leading to the pivotal steps of viral life cycle are still unclear. Here, we reported that ribonucleoside-diphosphate reductase subunit M2 (RRM2) plays a critical role during ALV-J infection by interacting with capsid protein P27 and activating Wnt/β-catenin signaling. We found that the expression of RRM2 is effectively increased during ALV-J infection, and that RRM2 facilitates ALV-J replication by interacting with viral capsid protein P27. Furthermore, ALV-J P27 activated Wnt/β-catenin signaling by promoting β-catenin entry into the nucleus, and RRM2 activated Wnt/β-catenin signaling by enhancing its phosphorylation at Ser18 during ALV-J infection. These data suggest that the upregulation of RRM2 expression by ALV-J infection favors viral replication in host cells via activating Wnt/β-catenin signaling. IMPORTANCE Our results revealed a novel mechanism by which RRM2 facilitates ALV-J growth. That is, the upregulation of RRM2 expression by ALV-J infection favors viral replication by interacting with capsid protein P27 and activating Wnt/β-catenin pathway in host cells. Furthermore, the phosphorylation of serine at position 18 of RRM2 was verified to be the important factor regulating the activation of Wnt/β-catenin signaling. This study provides insights for further studies of the molecular mechanism of ALV-J infection.
Topics: Animals; Avian Leukosis; Avian Leukosis Virus; beta Catenin; Capsid Proteins; Chickens; Wnt Signaling Pathway; Ribonucleoside Diphosphate Reductase
PubMed: 37582207
DOI: 10.1128/jvi.00267-23 -
Poultry Science Oct 2018In the current study, we sought to determine whether or not the endogenous retroviral ev21 influences feathering type of chickens, and if one mutation locus in the...
In the current study, we sought to determine whether or not the endogenous retroviral ev21 influences feathering type of chickens, and if one mutation locus in the unoccupied repeat (UR) region can be used to predict the corresponding feathering type and genotype. The distribution of ev21 as well as the mutation locus in UR and occupied site (OR) regions was detected in HY-line gray progenitor (HYGP) 4 lines, HY-line brown (HYB) and Taihang chickens (TH). Furthermore, a detection method for the genotype resulting in late feathering (LF) phenotype was developed by double PCR using C line of HYGP, C line of Dawu progenitor, commercial line of HY-line gray (HYG) males, LF males of TH and Bashang long-tail chickens (BS). Results indicated that a product of 7590 bp from the long fragment amplification was observed to be a partial segment of ev21, and was linked with the LF phenotype in HYGP but not in HYB and TH chickens. A total of 2 of 35 males and 10 of 29 females of TH LF chickens were found to be ev21 negative. HaeIII RFLP mutations of 1450 bp of UR, 1440 bp of OR, and 538 bp in the UR and OR common region were analyzed, and genotypic features at the locus correlated with the feathering type phenotype in HYGP, but exhibited no significant effects in HYB and TH chickens. The cut-off of relative intensity of 857 and 1305 bp from the double PCR for distinction between homozygous and heterozygous LF males was 1.37. In conclusion, ev21 and the HaeIII RFLP patterns within the locus in UR cannot be used for prediction of feathering type phenotypes in Chinese heritage chickens. However, the partial duplication of PRLR and SPEF2 were able to predict the LF phenotype. Therefore, the double PCR detecting products of 857 and 1305 bp described herein could be used for the accurate identification of genotypes influencing feathering type.
Topics: Animals; Avian Leukosis Virus; Avian Proteins; Chickens; Feathers; Female; Gene Duplication; Genes, Viral; Genotype; Male; Phenotype; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Viral Proteins
PubMed: 29924355
DOI: 10.3382/ps/pey231 -
Veterinary Microbiology Sep 2023While the presence of host cell proteins in virions and their role in viral life cycles have been demonstrated in various viruses, such characteristics have remained...
While the presence of host cell proteins in virions and their role in viral life cycles have been demonstrated in various viruses, such characteristics have remained largely unknown in avian leukosis virus (ALV). To investigate whether this is the case in ALV, we purified high-integrity and high-purity virions from the avian leukosis virus subgroup J (ALV-J) and subjected them to proteome analysis using nano LC-MS/MS. This analysis identified 53 cellular proteins that are incorporated into mature ALV-J virions, and we verified the reliability of the packaged cellular proteins through subtilisin digestion and immunoblot analysis. Functional annotation revealed the potential functions of these proteins in the viral life cycle and tumorigenesis. Overall, our findings have important implications for understanding the interaction between ALV-J and its host, and provide new insights into the cellular requirements that define ALV-J infection.
Topics: Animals; Chickens; Avian Leukosis Virus; Tandem Mass Spectrometry; Proteomics; Reproducibility of Results; Avian Leukosis
PubMed: 37536160
DOI: 10.1016/j.vetmic.2023.109821 -
Mediators of Inflammation 2021The aim of this study was to better understand the sequence characteristics and immune responses in avian leukosis virus subgroup J (ALV-J) infected yellow chicken...
The aim of this study was to better understand the sequence characteristics and immune responses in avian leukosis virus subgroup J (ALV-J) infected yellow chicken flocks in South China. We isolated four strains of ALV-J virus from these flocks, which were then identified by several methods, including subtype-specific polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay (IFA). All four viruses were sequenced for their complete genomes and named GD19GZ01, GD19GZ02, GD19GZ03, and GD19GZ04. In comparison with the reference sequence, the homology analysis showed that the and genes were relatively conserved, whereas contained much variation. Both GD19GZ01 and GD19GZ02 almost entirely lacked the rTM region and E element, while the latter was retained in GD19GZ03 and GD19GZ04. Moreover, the virus replication levels in GD19GZ03 and GD19GZ04were much higher than those in GD19GZ01 and GD19GZ02. And three virus recombination events in GD19GZ01 and GD19GZ02 were revealed by the results of PDR5 and SimPlot software analysis. Additionally, we found that some interferon-stimulating genes (, , , , and ) and inflammatory mediators (, , , , , and ) were significantly upregulated in the immune system organs of clinical chickens. Taken together, these findings clarify and reveal the sequence characteristics and trends in the variation of ALV-J infection in yellow chicken flocks of South China.
Topics: Animals; Avian Leukosis Virus; Chickens; China; Enzyme-Linked Immunosorbent Assay; Interleukin-10; Interleukin-4; Interleukin-6; Phylogeny
PubMed: 33628117
DOI: 10.1155/2021/6665871 -
Viruses May 2019The initial step of retrovirus entry-the interaction between the virus envelope glycoprotein trimer and a cellular receptor-is complex, involving multiple, noncontiguous... (Review)
Review
The initial step of retrovirus entry-the interaction between the virus envelope glycoprotein trimer and a cellular receptor-is complex, involving multiple, noncontiguous determinants in both proteins that specify receptor choice, binding affinity and the ability to trigger conformational changes in the viral glycoproteins. Despite the complexity of this interaction, retroviruses have the ability to evolve the structure of their envelope glycoproteins to use a different cellular protein as receptors. The highly homologous subgroup A to E Avian Sarcoma and Leukosis Virus (ASLV) glycoproteins belong to the group of class 1 viral fusion proteins with a two-step triggering mechanism that allows experimental access to intermediate structures during the fusion process. We and others have taken advantage of replication-competent ASLVs and exploited genetic selection strategies to force the ASLVs to naturally evolve and acquire envelope glycoprotein mutations to escape the pressure on virus entry and still yield a functional replicating virus. This approach allows for the simultaneous selection of multiple mutations in multiple functional domains of the envelope glycoprotein that may be required to yield a functional virus. Here, we review the ASLV family and experimental system and the reverse engineering approaches used to understand the evolution of ASLV receptor usage.
Topics: Animals; Avian Leukosis Virus; Avian Sarcoma Viruses; Chickens; Evolution, Molecular; Mutation; Receptors, Virus; Reverse Genetics; Sarcoma, Avian; Viral Envelope Proteins; Virus Internalization; Virus Replication
PubMed: 31151254
DOI: 10.3390/v11060497 -
Frontiers in Immunology 2022Avian Leukosis Virus Subgroup J (ALV-J) is a tumorigenic virus with high morbidity and rapid transmission. N6-methyladenosine (mA) is a common epigenetic modification...
Avian Leukosis Virus Subgroup J (ALV-J) is a tumorigenic virus with high morbidity and rapid transmission. N6-methyladenosine (mA) is a common epigenetic modification that may be closely related to the pathogenicity of ALV-J. Currently, there are no reports on whether mA modification is related to ALV-J induced tumor formation. In this study, we used methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to examine the differences in mA methylation and gene expression in normal livers and ALV-J-induced tumor livers systematically, with functional enrichment and co-expression analysis. The results identified 6,541 mA methylated peaks, mainly enriched in CDS, and more than 83% of the transcripts contained 1-2 mA peaks. For RNA-seq, 1,896 and 1,757 differentially expressed mRNAs and lncRNAs were identified, respectively. Gene enrichment analysis indicated that they may be involved in biological processes and pathways such as immunology-related and apoptosis. Moreover, we identified 17 lncRNAs, commonly existing in differently expressed methylome and transcriptome. Through co-expression analysis, 126 differentially expressed lncRNAs, and 18 potentially mA-related methyltransferases were finally identified and connected, suggesting that mA modifications might affect gene expression of lncRNAs and play a role in ALV-J induced tumor formation. This study provides the first comprehensive description of the mA expression profile in tumor livers induced by ALV-J infection in chickens, which provides a basis for studying the role of mA modification in ALV-J induced tumorigenesis. This study provides clues for studying the epigenetic etiology and pathogenesis of ALV-J.
Topics: Animals; Avian Leukosis; Avian Leukosis Virus; Carcinogenesis; Chickens; Liver; Methylation; RNA, Long Noncoding; Transcriptome
PubMed: 35529873
DOI: 10.3389/fimmu.2022.868892