Co-expression of Bovine leukemia virus and Bovine foamy virus-derived miRNAs in naturally infected cattle

Petersen, M. I.; Suarez Archilla, G.; Perez, C. V.; Gonzalez, D. D.; Trono, K. G.; Mongini, C.; Jaworski, J. P.; Carignano, H. A.

doi:10.1101/2025.02.21.639540

bioRxiv · 10.1101/2025.02.21.639540

Co-expression of Bovine leukemia virus and Bovine foamy virus-derived miRNAs in naturally infected cattle

Petersen, M. I.·Suarez Archilla, G.·Perez, C. V.·Gonzalez, D. D.·Trono, K. G.·Mongini, C.·Jaworski, J. P.·Carignano, H. A.

View original source ↗Export metadata ↓

Abstract

Among the viruses that encode miRNAs and infect cattle such as Bovine leukemia virus (BLV), Bovine foamy virus (BFV) and Bovine herpesviruses (BoHV), BLV has gained attention due to the critical role that BLV-miRNAs may play in inducing lymphosarcoma in infected animals. BLV is highly prevalent in the Americas and negatively affects dairy herds, primarily due to restrictions on the commercialization of dairy products from infected animals and a decrease in milk production. Mixed infections involving BLV and BFV appear to be common in cattle. Considering the ability of foamy viruses to cross species barriers, preventing their presence within the food chain is essential. We identified the co-expression of seven BLV-derived miRNAs (blv-miR-B1-3p, blv-miR-B2-5p, blv-miR-B2-3p, blv-miR-B3-5p, blv-miR-B3-3p, blv-miR-B4-3p and blv-miR-B5-5p) and three BFV-derived (bfv-miR-BF1-5p, bfv-miR-BF1-3p, and bfv-miR-BF2-5p) in naturally BLV-infected cows. Besides, seven differentially expressed bovine miRNAs (bta-miR-375, bta-miR-133a, bta-miR-677, bta-miR-1, bta-miR-3613a, bta-miR-9-5p and bta-miR-95) were identified between cows with high BLV proviral load and uninfected counterparts (fold change > |1.5| and q-value < 0.05). A comprehensive functional analysis of protein-protein interaction networks for genes targeted by both viral and host-derived miRNAs highlighted key pathways implicated in tumorigenesis and immune response. Although BLV and BFV derived miRNAs target different genes, their functional convergence may reflect coordinated viral modulation of host cellular processes, raising important concerns regarding their potential influence on disease severity and the increased dissemination of BFV. These findings offer new perspectives for creating diagnostic and treatment approaches to manage viral persistence and tumorigenesis in cattle. ImportanceThe Bovine leukemia virus (BLV) and Bovine foamy virus (BFV) are retroviruses that encode miRNAs and infect cattle. While the role of BFV-derived miRNAs remains unclear, BLV-miRNAs have gained attention for their potential involvement in oncogenesis. Mixed BLV-BFV infections are common and given foamy viruses potential to cross species barriers, it is essential to prevent their presence in the food chain. We reported the co-expression of three BFV-derived miRNAs and seven BLV-derived miRNAs in naturally infected cattle. A functional analysis of the protein-protein interaction graph of genes potentially targeted by both viral and host-derived miRNAs revealed key metabolic pathways associated with tumorigenesis and immune response regulation. The co-expression of BLV and BFV miRNAs suggests a potential functional interactions that may influence disease progression and BFV dissemination. These findings offer opportunities for developing diagnostic and therapeutic strategies to control viral persistence and tumor development in cattle.

Source connections

Published article ↗

Explore related subjects

microbiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Petersen, M. I., Suarez Archilla, G., Perez, C. V., Gonzalez, D. D., Trono, K. G., Mongini, C., Jaworski, J. P., Carignano, H. A.. 2025-02-23. Co-expression of Bovine leukemia virus and Bovine foamy virus-derived miRNAs in naturally infected cattle. https://doi.org/10.1101/2025.02.21.639540

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Extreme temperature exposure has negative demographic consequences for Sulfolobus acidocaldarius

Microorganisms inhabiting geothermal springs and volcanic systems experience fluctuating temperatures that can periodically exceed their upper thermal limits, but the demographic consequences of such exposure remain poorly understood. Here, we investigated demographic responses of the thermophilic archaeon Sulfolobus acidocaldarius to an extreme temperature (94.1{degrees}C) under two regimes: sustained exposure varying in duration, and episodic exposure interspersed with recovery at a permissive temperature (75{degrees}C). Under sustained exposure, populations showed no detectable loss of viability after 15 min but declined thereafter, decreasing by approximately five orders of magnitude after 120 min. Under episodic exposure, populations remained viable across nine exposure-recovery cycles but declined in density with successive cycles. Similar responses were observed for three strains, including a DNA mismatch repair knockout ({Delta}nucS), indicating that mismatch repair deficiency did not affect viability or recovery. Together, these results demonstrate that S. acidocaldarius can withstand brief and repeated exposure to near-boiling temperatures, with mortality determined primarily by cumulative exposure duration rather than a fixed thermal threshold.

microbiology↗

bioRxiv2026

Bacteriophage and Antibiotic Resistance Are Positively Associated across a Phylogenetically Diverse Set of Clinical Pseudomonas aeruginosa Isolates

Co-administration of phages and antibiotics has been proposed as a therapeutic approach against antibiotic-resistant bacteria. The relationship, however, between antibiotic resistance and phage resistance in clinical isolates is unclear. Here, we examine associations between phage and antibiotic resistance profiles across a panel of Pseudomonas aeruginosa clinical isolates from the Centers for Disease Control (CDC) and Food and Drug Administration (FDA) Antimicrobial Resistance Isolate (ARI) Bank comprising 55 clinical strains with full genome sequences and antibiotic susceptibility testing (AST) data for 11 clinically relevant antibiotics. As phages in this study, we use three well-characterized, morphologically distinct phages, OMKO1, Luz19, and PAML31-1. We screen for phage resistance using a growth suppression assay, then conduct statistical analysis against antibiotic MIC (Minimum Inhibitory Concentration) data provided by the CDC to define association patterns across this dataset. We find multiple significant susceptibility correlations between pairs of antibiotics and phages, and a positive overall association between average phage resistance and antibiotic resistance across the 55 strains, even controlling for phylogenetic associations (=0.358, p<0.005). We conclude that phage and antibiotic resistance are positively associated across this clinical isolate collection, suggesting that the two resistance phenotypes are not independent in P. aeruginosa. These findings have implications for the development of phage-antibiotic cocktails.

microbiology↗

bioRxiv2026

The Estuary Effect: Variations in Temperature and Salinity Alter msh Promoter Activity in Vibrio cholerae

Vibrio cholerae, the facultative pathogen underlying cholera, naturally inhabits warm aquatic estuaries. Environmental persistence is enhanced by the ability of V. cholerae to colonize host reservoirs and form multicellular biofilms, causing seasonally endemic outbreaks in many tropical regions. Most toxigenic strains utilize the type IVa mannose-sensitive hemagglutinin (MSHA) pilus for host reservoir colonization and biofilm formation. Temperature and salinity can alter V. cholerae biofilm formation, yet their impact on MSHA production specifically remains largely unknown. Here, we utilized transcriptional reporters of predicted msh promoters (msh-P1/msh-P2/msh-P3) and functional assays, to determine temperature and salinity impacts on msh expression and pilus biogenesis. Under standard laboratory conditions (30{degrees}C, 1% NaCl) only msh-P1/P2 are active and inversely-coordinated with one another. Both msh-P1/P2 activity were elevated by high temperature (37{degrees}C) and low salinity (0.25%/0.5% NaCl), and reduced by low temperature (20{degrees}C/25{degrees}C) and high salinity (2%/3% NaCl). Temperature-mediated alterations in promoter activity were not immediately reflected in changes to cell-surface MSHA levels, whereas high salinity led to decreased MSHA production. Combining high temperature (37{degrees}C) and high salinity (2%/3% NaCl), attenuated the salinity-mediated reduction of msh-P1/P2 activity. Biofilm biomass levels were only substantially heightened at 25{degrees}C and 20{degrees}C, likely a result of no temperature-dependent changes in cell-surface MSHA, and additional temperature-controlled biofilm regulation previously described. We also found msh-P1/P2 promoter activity and MSHA production varies widely across toxigenic O1 and O139 serogroups despite complete sequence homology. These results shed new light on how key signals regulate MSHA pilus production to support V. cholerae persistence in aquatic environments.

microbiology↗