Spontaneous virus reactivation in cattle chronically infected with bovine leukemia virus

Background: The absence of virus expression during the chronic stage of bovine leukemia virus (BLV) infection and its reactivation upon ex vivo culture has become a long-lived Dogma. During the chronic stage of BLV infection the immune response limits viral replication and the mitotic division of latently infected cells, carrying BLV provirus, allows viral expansion and disease progression towards a lymphoproliferative disorder. Several stressor factors have been associated with animal production and handling. As natural mediator of stress, glucocorticoids are strong immunosuppressive agents; moreover, they can bind long-terminal repeat region of retroviruses and induce viral expression. In the present study, we present a case report describing the spontaneous reactivation of BLV infection in naturally infected cattle. Case presentation: In order to investigate if virus reactivation occurred in vivo during the course of BLV infection, we followed up for 328 days one Holstein cow (> 3 years) chronically infected with BLV which presented high-proviral loads. This animal was neither lactating nor pregnant. Furthermore, we investigated if a stressor stimulus, in this case the administration of a synthetic glucocorticoid (dexamethasone), could impact the course of BLV infection in three additional cattle. For the first time, we observed a high level of BLV transcripts in a total of four cattle chronically infected with BLV. The detection of viral transcripts corresponding to pol gene strongly suggests virus reactivation in these animals. Interestingly, this simultaneous virus reactivation was unrelated to dexamethasone treatment. Conclusions: We reported for the first time spontaneous and high level of BLV transcriptional activation in cattle chronically infected with BLV. Although virus reactivation was unrelated to dexamethasone treatment, other stressor stimuli might have influenced this outcome. Future studies will be necessary to understand these observations, since the spontaneous virus reactivation presented here might have implications on BLV pathogenesis and transmission.Instituto de VirologíaFil: Jaworski, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Carignano, Hugo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentin

Towards inclusive funding practices for early career researchers

Securing research funding is a challenge faced by most scientists in academic institutions worldwide. Funding success rates for all career stages are low, but the burden falls most heavily on early career researchers (ECRs). These are young investigators in training and new principal investigators who have a shorter track record. ECRs are dependent on funding to establish their academic careers. The low number of career development awards and the lack of sustained research funding result in the loss of ECR talent in academia. Several steps in the current funding process, from grant conditions to review, play significant roles in the distribution of funds. Furthermore, there is an imbalance where certain research disciplines and labs of influential researchers receive more funding. As a group of ECRs with global representation, we examined funding practices, barriers, and facilitators to the current funding systems. We also identified alternatives to the most common funding distribution practices, such as diversifying risk or awarding grants on a partly random basis. Here, we detail recommendations for funding agencies and grant reviewers to improve ECR funding prospects worldwide and promote a fairer and more inclusive funding landscape for ECRs.Instituto de VirologíaFil: de Winde, Charlotte M. University College London. MRC Laboratory for Molecular Cell Biology; Reino UnidoFil: de Winde, Charlotte M. Amsterdam University Medical Center. Department of Molecular Cell Biology & Immunology; Países BajosFil: Sarabipour, Sarvenaz. Johns Hopkins University. Department of Biomedical Engineering. Institute for Computational Medicine; Estados UnidosFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Davla, Sejal. City University of New York. Advanced Science Research Center; Estados UnidosFil: Eccles, David. Malaghan Institute of Medical Research; Nueva ZelandaFil: Hainer, Sarah J. University of Pittsburgh. Department of Biological Sciences; Estados UnidosFil: Haidar, Mansour. Hasselt University; BélgicaFil: Ilangovan, Vinodh. Aarhus University; DinamarcaFil: Jadavji, Nafisa M. Midwestern University. Department of Biomedical Sciences; Estados UnidosFil: Jadavji, Nafisa M. Carleton University. Department of Neuroscience; CanadáFil: Kritsiligkou, Paraskevi. German Cancer Research Center; AlemaniaFil: Lee, Tai-Ying. University of Oxford; Reino UnidoFil: Ólafsdóttir, H. Freyja. Radboud University. Donders Institute for Brain, Cognition and Behaviour; Países Bajo

BLV: Lessons on vaccine development

Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.Fil: Abdala, Alejandro Ariel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Brossel, Hélène. Université de Liège; BélgicaFil: Calvinho, Luis Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Carignano, Hugo Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Franco, Lautaro Nahuel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Gazon, Hélène. Université de Liège; BélgicaFil: Gillissen, Christelle. Université de Liège; BélgicaFil: Hamaidia, Malik. Université de Liège; BélgicaFil: Hoyos, Clotilde. Université de Liège; BélgicaFil: Jacques, Jean Rock. Université de Liège; BélgicaFil: Joris, Thomas. Université de Liège; BélgicaFil: Laval, Florent. Université de Liège; BélgicaFil: Petersen Cruceño, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Porquet, Florent. Université de Liège; BélgicaFil: Porta, Natalia Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Ruiz, Vanesa. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Safari, Roghaiyeh. Université de Liège; BélgicaFil: Suárez Archilla, Guillermo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Willems, Luc. Université de Liège; Bélgic

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazonia Sustentavel, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.Keywords: Social–ecological systems, Tropical forests, Land use, Interdisciplinary research, Sustainability, Trade-off

Bovine leukemia virus encoded blv-miR-b4-3p microRNA is associated with reduced expression of anti-oncogenic gene in vivo

Bovine leukemia virus (BLV) is a retrovirus that causes malignant B-cell lymphoma in up to ten-percent of infected cattle. To date, the mechanisms of BLV linked to malignant transformation remain elusive. Although BLV-encoded miRNAs have been associated with the regulation of different genes involved in oncogenic pathways, this association has not been evaluated in cattle naturally infected with BLV. The objective of this study was to determine the relative expression of BLV-encoded miRNA blv-miR-b4-3p, the host analogous miRNA bo-miR-29a and a couple of potential target mRNAs (HBP-1 and PXDN, with anti-tumorigenic function in B-cells), in cattle naturally infected with BLV compared to uninfected animals (control group). We observed that PXDN was significantly downregulated in BLV-infected cattle (P = 0.03). Considering the similar expression of endogenous bo-miR-29a in both animal groups, the downregulation of PXDN in BLV-naturally infected cattle could be linked to blv-miR-b4-3p expression in these animals. Knowing that PXDN is involved in anti-tumoral pathways in B-cells, the results presented here suggest that blv-miR-b4-3p might be involved in BLV tumorigenesis during natural infection with BLV in cattle.Instituto de VirologíaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Petersen, Marcos Iván. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Mongini, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonzalez, Diego D..Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Gonzalez, Diego D. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jaworski, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Jaworski, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Bovine leukemia virus becomes established in dairy herds before the first lactation

peer reviewedaudience: researcher, professional, studentIn this work, we studied seven groups of pregnant heifers from a consortium of dairy farms heavily infected with bovine leukemia virus (BLV). ELISA testing showed that the seroprevalence ranges of BLV in heifers between 36.1 and 66.5 %. No significant differences in proviral load were found when comparing heifers with adult cattle. Before their first delivery, more than 9.8 % of heifers show a high proviral load. Because BLV infection can occur during the first two years of life, the rationale of any strategy should be to take action as early as possible after birth

Weighted single-step genome-wide association analyses for milk traits in Holstein and Holstein x Jersey crossbred dairy cattle

The purpose of this study was to identify genomic regions explaining a major proportion of the genetic variance in milk production and milk fat and protein content on a commercial herd of Holstein and Holstein x Jersey crossbred cattle bred in an extensive grazing system. We analyzed 305-day cumulative milk production records from 18876 cows at first lactation, of which 16907 and 16735 had milk fat and protein content records during the same period. After data quality control, genotypes from 998 animals on 40417 SNPs included in the Illumina Bovine SNP50 v2 BeadChip were available. Weighted single-step genome-wide association studies were conducted for milk yield (MY), fat content (FC) and protein content (PC). Windows of 10 adjacent single nucleotide polymorphisms explaining more than 0.31% of the genetic variance were considered relevant. Protein-coding genes located within those windows were retrieved, their functional relevance was assessed, the main functional categories and biological processes represented by them were identified, and an overrepresentation test was performed. Relevant windows for MY, FC and PC were 52, 57 and 56, and harbored 304, 293 and 269 proteincoding genes, respectively. The proteins encoded by those genes were mainly involved in cellular, metabolic and biological regulation processes. Cellular response to cytokine stimulus, GTPase activity and GTP binding, and heterotrimeric G-protein were the main overrepresented biological process, molecular functions, and protein class, respectively. Among the candidate genes found, some previously reported genes associated with milk traits, such as CDH2, DGAT1, GRINA, LIPA, PGR, RPGRIP1L, VPS28, MAF1, and FTO were identified. However, novel candidate genes related to transcriptional regulation and transporter activity were also found. These results contribute to a better understanding of the loci influencing milk traits in the main dairy cattle breeds in Argentina.Instituto de GenéticaFil: Raschia, Maria Agustina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Nani, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Amadio, Ariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maizon, Daniel Omar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; ArgentinaFil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentin

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle

In dairy cattle infected with bovine leukemia virus (BLV), the proviral load (PVL) level is directly related to the viral transmission from infected animals to their healthy herdmates. Two contrasting phenotypic groups can be identified when assessing PVL in peripheral blood of infected cows. A large number of reports point to bovine genetic variants (single nucleotide polymorphisms) as one of the key determinants underlying PVL level. However, biological mechanisms driving BLV PVL profiles and infection progression in cattle have not yet been elucidated. In this study, we evaluated whether a set of candidate genes affecting BLV PVL level according to whole genome association studies are differentially expressed in peripheral blood mononuclear cells derived from phenotypically contrasting groups of BLV-infected cows. During a 10-mo-long sampling scheme, 129 Holstein cows were phenotyped measuring anti-BLV antibody levels, PVL quantification, and white blood cell subpopulation counts. Finally, the expression of 8 genes (BOLA-DRB3, PRRC2A, ABT1, TNF, BAG6, BOLA-A, LY6G5B, and IER3) located within the bovine major histocompatibility complex region harboring whole genome association SNP hits was evaluated in 2 phenotypic groups: high PVL (n = 7) and low PVL (n = 8). The log2 initial fluorescence value (N0) transformed mean expression values for the ABT1 transcription factor were statistically different in high- and low-PVL groups, showing a higher expression of the ABT1 gene in low-PVL cows. The PRRC2A and IER3 genes had a significant positive (correlation coefficient = 0.61) and negative (correlation coefficient = −0.45) correlation with the lymphocyte counts, respectively. Additionally, the relationships between gene expression values and lymphocyte counts were modeled using linear regressions. Lymphocyte levels in infected cows were better explained (coefficient of determination = 0.56) when fitted a multiple linear regression model using both PRRC2A and IER3 expression values as independent variables. The present study showed evidence of differential gene expression between contrasting BLV infection phenotypes. These genes have not been previously related to BLV pathobiology. This valuable information represents a step forward in understanding the BLV biology and the immune response of naturally infected cows under a commercial milk production system. Efforts to elucidate biological mechanisms leading to BLV infection progression in cows are valuable for BLV control programs. Further studies integrating genotypic data, global transcriptome analysis, and BLV progression phenotypes are needed to better understand the BLV–host interaction.Instituto de VirologíaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Petersen, Marcos Iván. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Suarez Archilla, Guillermo. INTA. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Caffaro, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Alvarez, Irene. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Miretti, Marcos Mateo. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Instituto de Biología Subtropical. Grupo de Investigación en Genética Aplicada; ArgentinaFil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Trono, Karina Gabriela. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentin

Bovine leukemia virus p24 antibodies reflect blood proviral load

Abstract Background Bovine leukemia virus (BLV) is worldwide distributed and highly endemic in Argentina. Among the strategies to prevent BLV dissemination, a control plan based on the selective segregation of animals according to their proviral load (PVL) is promising for our dairy productive system. The objective of this work was to study the relationship between the blood PVL and the antibody level, in order to identify whether the individual humoral response, i.e. the anti-p24 or anti-whole-BLV particle, could be used as a marker of the blood level of infection and thus help to recruit animals that may pose a lower risk of dissemination under natural conditions. Results The prevalence of p24 antibodies on the 15 farms studied was over 66%. The prevalence of p24 and whole-BLV antibodies and PVL quantification were analyzed in all the samples (n = 196) taken from herds T1 and 51. ROC analysis showed a higher AUC for p24 antibodies than whole-BLV antibodies (Zreactivity: 3.55, P titer: 2.88, P T1 = 0.7, P 51 = 0.71, P  Conclusions We found that the humoral response reflected the level of in vivo infection, and may therefore have useful epidemiological applications. Whereas the quantitative evaluation of blood proviral load using real-time PCR is expensive and technically demanding, the measurement of antibodies in blood by ELISA is relatively straightforward and could therefore constitute a cost-effective tool in a BLV control intervention strategy, especially in highly infected herds such as Argentinean dairy ones.</p

Bovine leukemia virus p24 antibodies reflect blood proviral load

BACKGROUND: Bovine leukemia virus (BLV) is worldwide distributed and highly endemic in Argentina. Among the strategies to prevent BLV dissemination, a control plan based on the selective segregation of animals according to their proviral load (PVL) is promising for our dairy productive system. The objective of this work was to study the relationship between the blood PVL and the antibody level, in order to identify whether the individual humoral response, i.e. the anti-p24 or anti-whole-BLV particle, could be used as a marker of the blood level of infection and thus help to recruit animals that may pose a lower risk of dissemination under natural conditions. RESULTS: The prevalence of p24 antibodies on the 15 farms studied was over 66%. The prevalence of p24 and whole-BLV antibodies and PVL quantification were analyzed in all the samples (n = 196) taken from herds T1 and 51. ROC analysis showed a higher AUC for p24 antibodies than whole-BLV antibodies (Z(reactivity): 3.55, P < 0.001; Z(titer): 2.88, P < 0.01), and as consequence a better performance to predict the proviral load status in herd 51. No significant differences were found between the performance of p24 and whole-BLV antibodies in herd T1. A significant positive correlation was observed between PVL values and p24 antibody reactivity in both farms (r (T1) = 0.7, P < 0.001, r (51) = 0.71, P < 0.0001). The analysis was extended to the whole number of weak p24 antibody reactors (n = 311) of the other 13 farms. The mean of high PVL reactors within weak p24 reactors was 17.38% (SD = 8.92). In 5/15 farms, the number of weak p24 reactors with high PVL was lower than 10%. CONCLUSIONS: We found that the humoral response reflected the level of in vivo infection, and may therefore have useful epidemiological applications. Whereas the quantitative evaluation of blood proviral load using real-time PCR is expensive and technically demanding, the measurement of antibodies in blood by ELISA is relatively straightforward and could therefore constitute a cost-effective tool in a BLV control intervention strategy, especially in highly infected herds such as Argentinean dairy ones