Andrés Cara, Damián de

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https://academica-e.unavarra.es/handle/2454/48531

Last Name

Andrés Cara

First Name

Damián de

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Instituto de Agrobiotecnología (IdAB)

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0000-0001-7302-807X

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4002

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Open Access
Detection of PrPSc in lung and mammary gland is favored by the presence of Visna/maedi virus lesions in naturally coinfected sheep
(EDP Sciences, 2010) Salazar, Eider; Monleón, Eva; Bolea, Rosa; Acín, Cristina; Pérez, Marta María; Álvarez, Neila; Leginagoikoa, Iratxe; Juste, Ramón; Minguijón, Esmeralda; Reina Arias, Ramsés; Glaría Ezquer, Idoia; Berriatua, Eduardo; Andrés Cara, Damián de; Badiola, Juan José; Amorena Zabalza, Beatriz; Luján, Lluís; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
There are few reports on the pathogenesis of scrapie (Sc) and Visna/maedi virus (VMV) coinfections. The aim of this work was to study in vivo as well as post mortem both diseases in 91 sheep. Diagnosis of Sc and VMV infections allowed the distribution of animals into five groups according to the presence (+) or absence ( ) of infection by Sc and VMV: Sc /VMV , Sc /VMV+, Sc+/VMV and Sc+/ VMV+. The latter was divided into two subgroups, with and without VMV-induced lymphoid follicle hyperplasia (LFH), respectively. In both the lung and mammary gland, PrPSc deposits were found in the germinal center of hyperplasic lymphoid follicles in the subgroup of Sc+/VMV+ having VMV-induced LFH. This detection was always associated with (and likely preceded by) PrPSc observation in the corresponding lymph nodes. No PrPSc was found in other VMV-associated lesions. Animals suffering from scrapie had a statistically significantly lower mean age than the scrapie free animals at the time of death, with no apparent VMV influence. ARQ/ARQ genotype was the most abundant among the 91 ewes and the most frequent in scrapie-affected sheep. VMV infection does not seem to influence the scrapie risk group distribution among animals from the five groups established in this work. Altogether, these data indicate that certain VMVinduced lesions can favor PrPSc deposits in Sc non-target organs such as the lung and the mammary gland, making this coinfection an interesting field that warrants further research for a better comprehension of the pathogenesis of both diseases.
Open Access
Ovine TRIM5α can restrict visna/maedi virus
(American Society for Microbiology, 2012) Jauregui, Paula; Crespo Otano, Helena; Glaría Ezquer, Idoia; Luján, Lluís; Contreras, A.; Rosati, Sergio; Andrés Cara, Damián de; Amorena Zabalza, Beatriz; Towers, G. J.; Reina Arias, Ramsés; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua; Gobierno de Navarra / Nafarroako Gobernua, IIQ14064.RI1
The restrictive properties of tripartite motif-containing 5 alpha (TRIM5α) from small ruminant species have not been explored. Here, we identify highly similar TRIM5α sequences in sheep and goats. Cells transduced with ovine TRIM5α effectively restricted the lentivirus visna/maedi virus DNA synthesis. Proteasome inhibition in cells transduced with ovine TRIM5α restored restricted viral DNA synthesis, suggesting a conserved mechanism of restriction. Identification of TRIM5α active molecular species may open new prophylactic strategies against lentiviral infections.
Open Access
Small ruminant lentiviruses: genetic variability, tropism and diagnosis
(MDPI, 2013) Ramírez Álvarez, Hugo; Reina Arias, Ramsés; Amorena Zabalza, Beatriz; Andrés Cara, Damián de; Martínez, Humberto A.; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Small ruminant lentiviruses (SRLV) cause a multisystemic chronic disease affecting animal production and welfare. SRLV infections are spread across the world with the exception of Iceland. Success in controlling SRLV spread depends largely on the use of appropriate diagnostic tools, but the existence of a high genetic/antigenic variability among these viruses, the fluctuant levels of antibody against them and the low viral loads found in infected individuals hamper the diagnostic efficacy. SRLV have a marked in vivo tropism towards the monocyte/macrophage lineage and attempts have been made to identify the genome regions involved in tropism, with two main candidates, the LTR and env gene, since LTR contains primer binding sites for viral replication and the env-encoded protein (SU ENV), which mediates the binding of the virus to the host’s cell and has hypervariable regions to escape the humoral immune response. Once inside the host cell, innate immunity may interfere with SRLV replication, but the virus develops counteraction mechanisms to escape, multiply and survive, creating a quasi-species and undergoing compartmentalization events. So far, the mechanisms of organ tropism involved in the development of different disease forms (neurological, arthritic, pulmonary and mammary) are unknown, but different alternatives are proposed. This is an overview of the current state of knowledge on SRLV genetic variability and its implications in tropism as well as in the development of alternative diagnostic assays.
Open Access
Identification of the ovine mannose receptor and its possible role in Visna/Maedi virus infection
(BioMed Central, 2011) Crespo Otano, Helena; Reina Arias, Ramsés; Glaría Ezquer, Idoia; Ramírez Álvarez, Hugo; Andrés, Ximena de; Jauregui, Paula; Luján, Lluís; Martínez Pomares, Luisa; Amorena Zabalza, Beatriz; Andrés Cara, Damián de; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
This study aims to characterize the mannose receptor (MR) gene in sheep and its role in ovine visna/maedi virus (VMV) infection. The deduced amino acid sequence of ovine MR was compatible with a transmembrane protein having a cysteine-rich ricin-type amino-terminal region, a fibronectin type II repeat, eight tandem C-type lectin carbohydrate-recognition domains (CRD), a transmembrane region, and a cytoplasmic carboxy-terminal tail. The ovine and bovine MR sequences were closer to each other compared to human or swine MR. Concanavalin A (ConA) inhibited VMV productive infection, which was restored by mannan totally in ovine skin fibroblasts (OSF) and partially in blood monocyte-derived macrophages (BMDM), suggesting the involvement of mannosylated residues of the VMV ENV protein in the process. ConA impaired also syncytium formation in OSF transfected with an ENV-encoding pN3-plasmid. MR transcripts were found in two common SRLV targets, BMDM and synovial membrane (GSM) cells, but not in OSF. Viral infection of BMDM and especially GSM cells was inhibited by mannan, strongly suggesting that in these cells the MR is an important route of infection involving VMV Env mannosylated residues. Thus, at least three patterns of viral entry into SRLV-target cells can be proposed, involving mainly MR in GSM cells (target in SRLV-induced arthritis), MR in addition to an alternative route in BMDM (target in SRLV infections), and an alternative route excluding MR in OSF (target in cell culture). Different routes of SRLV infection may thus coexist related to the involvement of MR differential expression.
Open Access
Expression analysis of lung miRNAs responding to ovine VM virus infection by RNA-seq
(BioMed Central, 2019) Bilbao Arribas, Martin; Abendaño, Naiara; Varela Martínez, Endika; Reina Arias, Ramsés; Andrés Cara, Damián de; Jugo, Begoña M.; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Background: MicroRNAs (miRNAs) are short endogenous, single-stranded, noncoding small RNA molecules of approximately 22 nucleotides in length. They regulate gene expression posttranscriptionally by silencing mRNA expression, thus orchestrating many physiological processes. The Small Ruminant Lentiviruses (SRLV) group includes the Visna Maedi Virus (VMV) and Caprine Arthritis Encephalitis (CAEV) viruses, which cause a disease in sheep and goats characterized by pneumonia, mastitis, arthritis and encephalitis. Their main target cells are from the monocyte/macrophage lineage. To date, there are no studies on the role of miRNAs in this viral disease. Results: Using RNA-seq technology and bioinformatics analysis, the expression levels of miRNAs during different clinical stages of infection were studied. A total of 212 miRNAs were identified, of which 46 were conserved sequences in other species but found for the first time in sheep, and 12 were completely novel. Differential expression analysis comparing the uninfected and seropositive groups showed changes in several miRNAs; however, no significant differences were detected between seropositive asymptomatic and diseased sheep. The robust increase in the expression level of oar-miR-21 is consistent with its increased expression in other viral diseases. Furthermore, the target prediction of the dysregulated miRNAs revealed that they control genes involved in proliferation-related signalling pathways, such as the PI3K-Akt, AMPK and ErbB pathways. Conclusions: To the best of our knowledge, this is the first study reporting miRNA profiling in sheep in response to SRLV infection. The known functions of oar-miR-21 as a regulator of inflammation and proliferation appear to be a possible cause of the lesions caused in the sheep's lungs. This miRNA could be an indicator for the severity of the lung lesions, or a putative target for therapeutic intervention.
Open Access
Immunization against small ruminant lentiviruses
(MDPI, 2013) Reina Arias, Ramsés; Andrés Cara, Damián de; Amorena Zabalza, Beatriz; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua; Gobierno de Navarra / Nafarroako Gobernua: IIQ14064.RI1
Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV) in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease.
Open Access
Iberian red deer: paraphyletic nature at mtDNA but nuclear markers support its genetic identity
(Wiley, 2016) Carranza, Juan; Salinas, María; Andrés Cara, Damián de; Pérez González, Javier; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Red deer populations in the Iberian glacial refugium were the main source for postglacial recolonization and subspecific radiation in north-western Europe. However, the phylogenetic history of Iberian red deer (Cervus elaphus hispanicus) and its relationships with northern European populations remain uncertain. Here, we study DNA sequences at the mitochondrial control region along with STR markers for over 680 specimens from all the main red deer populations in Spain and other west European areas. Our results from mitochondrial and genomic DNA show contrasting patterns, likely related to the nature of these types of DNA markers and their specific processes of change over time. The results, taken together, bring support to two distinct, cryptic maternal lineages for Iberian red deer that predated the last glacial maximum and that have maintained geographically well differentiated until present. Haplotype relationships show that only one of them contributed to the northern postglacial recolonization. However, allele frequencies of nuclear markers evidenced one main differentiation between Iberian and northern European subspecies although also supported the structure of both matrilines within Iberia. Thus, our findings reveal a paraphyletic nature for Iberian red deer but also its genetic identity and differentiation with respect to northern subspecies. Finally, we suggest that maintaining the singularity of Iberian red deer requires preventing not only restocking practices with red deer specimens belonging to other European populations but also translocations between both Iberian lineages.
Open Access
Nuevos avances para el desarrollo de vacunas frente a lentivirus
(Interempresasmedia, 2020) Reina Arias, Ramsés; Nistal Villán, Estanislao; Pablo Maiso, Lorena de; Echeverría Garín, Irache; Glaría Ezquer, Idoia; Andrés Cara, Damián de; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura
La infección de células ovinas por un virus murino no patogénico es capaz de interferir en la replicación de virus patogénicos como el Maedi Visna. El éxito en la defensa está condicionado por la capacidad inicial de respuesta con la que cuentan casi todas las células de los organismos vivos, participando en la inmunidad innata frente a cualquier infección.
Open Access
Growth performance and clinicopathological analyses in lambs repetitively inoculated with aluminum-hydroxide containing vaccines or aluminum-hydroxide only
(MDPI, 2021) Miguel, Ricardo de; Asín, Javier; Rodríguez Largo, Ana; Echeverría Garín, Irache; Lacasta, Delia; Andrés Cara, Damián de; Reina Arias, Ramsés; Pinczowski, Pedro; Gimeno, Marina; Molín, Jéssica; Fernández, Antonio; Blas, Ignacio de; Pérez, Marta María; Luján, Lluís; Ciencias; Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Aluminum (Al) hydroxide is an effective adjuvant used in sheep vaccines. However, Al-adjuvants have been implicated as potential contributors to a severe wasting syndrome in sheep— the so-called ovine autoimmune-inflammatory syndrome induced by adjuvants (ASIA syndrome). This work aimed to characterize the effects of the repetitive injection of Al-hydroxide containing products in lambs. Four flocks (Flocks 1–4; n = 21 each) kept under different conditions were studied. Three groups of seven lambs (Vaccine, Adjuvant-only, and Control) were established in each flock. Mild differences in average daily gain and fattening index were observed, indicating a reduced growth performance in Vaccine groups, likely related to short-term episodes of pyrexia and decreased daily intake. Clinical and hematological parameters remained within normal limits. Histology showed no significant differences between groups, although there was a tendency to present a higher frequency of hyperchromatic, shrunken neurons in the lumbar spinal cord in the Adjuvant-only group. Although Al-hydroxide was linked to granulomas at the injection site and behavioral changes in sheep, the results of the present experimental work indicate that injected Al-hydroxide is not enough to fully reproduce the wasting presentation of the ASIA syndrome. Other factors such as sex, breed, age, production system, diet or climate conditions could play a role.
Open Access
Multi-platform detection of small ruminant lentivirus antibodies and provirus as biomarkers of production losses
(Frontiers Media, 2020) Echeverría Garín, Irache; Miguel, Ricardo de; Pablo Maiso, Lorena de; Glaría Ezquer, Idoia; Benito, Alfredo A.; Blas, Ignacio de; Andrés Cara, Damián de; Luján, Lluís; Reina Arias, Ramsés; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura
Small ruminant lentiviruses (SRLVs) are endemic in most areas of Europe, causing a chronic infection and a multisystemic disease affecting the udder, carpal joints, lungs, and central nervous system. Due to the lack of treatments and protective vaccination strategies, infection control is focused on the identification of infected animals through serological or molecular techniques. However, antigenic and genetic heterogeneity of SRLVs represent a clear drawback for diagnosis. Infected animals may present lower animal production parameters such as birth weight or milk production and quality, depending on productive systems considered and, likely, to the diagnostic method applied. In this study, four sheep flocks dedicated to dairy or meat production were evaluated using three different ELISA and two PCR strategies to classify animal population according to SRLV infection status. Productive parameters were recorded along one whole lactation or reproductive period and compared between positive and negative animals. SRLV was present in 19% of the total population, being unequally distributed in the different flocks. Less than half of the infected animals were detected by a single diagnostic method, highlighting the importance of combining different diagnostic techniques. Statistical analysis employing animal classification using all the diagnostic methods associated lambing size, lamb weight at birth, and daily weight gain with SRLV infection status in meat flocks. Milk production, somatic cell count, fat, and protein content in the milk were associated with SRLV infection in dairy flocks, to a greater extent in the flock showing higher seroprevalence. A multi-platform SRLV diagnostic strategy was useful for ensuring correct animal classification, thus validating downstream studies investigating production traits.