Reina Arias, Ramsés

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https://academica-e.unavarra.es/handle/2454/49837

Last Name

Reina Arias

First Name

Ramsés

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Instituto de Agrobiotecnología (IdAB)

ORCID

0000-0003-1265-9139

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5614

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Open Access
Replication of small ruminant lentiviruses in aluminum hydroxide-induced granulomas in sheep: a potential new factor for viral dissemination
(American Society for Microbiology, 2021) Echeverría Garín, Irache; Miguel, Ricardo de; Asín, Javier; Rodríguez Largo, Ana; Fernández, Antonio; Pérez, Marta María; Andrés Cara, Damián de; Luján, Lluís; Reina Arias, Ramsés; Ciencias; Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Aluminum (Al)-based salts are widely used adjuvants in ruminants and other species to strengthen the immune response elicited against vaccine antigen(s). However, they can lead to the formation of long-lasting granulomas composed of abundant activated macrophages. Small ruminant lentiviruses (SRLV) are widely distributed macrophage-tropic retroviruses that cause persistent infections in sheep and goats. Infected monocytes/macrophages and dendritic cells establish an inflammatory microenvironment that eventually leads to clinical manifestations. The aim of this work was to study the effect of Al-induced granulomas in the replication and pathogenesis of SRLV. Eleven adult, naturally SRLV-infected sheep showing clinical arthritis were distributed in vaccine (n = 6), adjuvant-only (n = 3), and control (n = 2) groups and inoculated with commercial Al-based vaccines, Al hydroxide adjuvant alone, or phosphate-buffered saline, respectively. In vitro studies demonstrated viral replication in Al-induced granulomas in 5 out of 10 sheep. Immunohistochemistry (IHC) evinced granular, intracytoplasmic SRLV presence in macrophages within granulomas. Viral sequences obtained from granulomas, blood monocytes, and other tissues were highly similar in most animals, suggesting virus circulation among body compartments. However, notable differences between isolated strains in granulomas and other tissues in specific animals were also noted. Interestingly, the B2 subtype was the most commonly found SRLV genotype, reaching a wider body distribution than previously described. Recombination events between genotypes B2 and A3 along the gag region were identified in two sheep. Our results indicate that Al-hydroxide-derived granulomas may represent an ideal compartment for SRLV replication, perhaps altering natural SRLV infection by providing a new, suitable target tissue. IMPORTANCE Granulomas are inflammation-derived structures elicited by foreign bodies or certain infections. Aluminum adjuvants included in vaccines induce granulomas in many species. In sheep, these are persistent and consist of activated macrophages. Small ruminant lentiviruses (SRLV), which are macrophage-tropic lentiviruses, cause a chronic wasting disease affecting animal welfare and production. Here, we studied the occurrence of SRLV in postvaccination granulomas retrieved from naturally infected ewes after vaccination or inoculation with aluminum only. SRLV infection was confirmed in granulomas by identification of viral proteins, genomic fragments, and enzymatic activity. The infecting SRLV strain, previously found exclusively in carpal joints, reached the central nervous system, suggesting that occurrence of SRLV in postvaccination granulomas may broaden tissue tropism. SRLV recombination was detected in inoculated animals, a rare event in sheep lentiviruses. Potentially, virus-host interactions within granulomas may modify viral pathogenesis and lead to more widespread infection.
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
Molecular signature of aluminum hydroxide adjuvant in ovine PBMCs by integrated mRNA and microRNA transcriptome sequencing
(Frontiers Media, 2018) Varela Martínez, Endika; Abendaño, Naiara; Asín, Javier; Sistiaga Poveda, Maialen; Pérez, Marta María; Reina Arias, Ramsés; Andrés Cara, Damián de; Luján, Lluís; Jugo, Begoña M.; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2,473; 2,980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-κB signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.
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
Lack of relationship between Visna/maedi infection and scrapie resistance genetic markers
(Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA), 2014) Salazar, Eider; Berriatua, Eduardo; Pérez, Marta María; Marín, Belén; Acín, Cristina; Martín Burriel, Inmaculada; Reina Arias, Ramsés; Andrés Cara, Damián de; Amorena Zabalza, Beatriz; Badiola, Juan José; Luján, Lluís; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
The relationship between Visna/maedi virus (VMV) antibody status and scrapie genetic resistance of 10,611 Rasa Aragonesa sheep from 17 flocks in Aragón (Spain) was investigated. The fifteen most common PRNP gene haplotypes and genotypes were identified and the genotypes were classified into the corresponding scrapie risk groups (groups 1 to 5). ARQ (93.3%) and ARR (31.8%) were the most common haplotypes and ARQ/ARQ (56%) and ARR/ARQ (25.6%) were the most common genotypes. The frequencies of scrapie risk groups 1, 2, 3, 4 and 5 were 3.3%, 27.3%, 63.5%, 1.2% and 4.8%, respectively. Overall Visna/maedi seroprevalence was 53% and flock seroprevalence ranged between 21-86%. A random effects logistic regression model indicated that sheep VMV serological status (outcome variable) was not associated with any particular scrapie risk group. Instead, VMV seropositivity progressively increased with age, was signif icantly greater in females compared to males and varied between flocks. The absence of a relationship between VMV infection and scrapie genotypes is important for VMV control and specifically for sheep participating in an ELISA-based Visna/maedi control program.