Effect of bovine viral diarrhea virus on subsequent infectivity of bovine gammaherpesvirus 4 in endometrial cells in primary culture: An in vitro model of viral co-infection.

Bovine viral diarrhea virus (BVDV) and bovine gammaherpesvirus 4 (BoHV-4) infect the uterus of cattle, being responsible for huge economic losses. Most of the pathogenesis of BoHV-4 in the bovine reproductive tract has been elucidated by conducting tests on primary cultures. Thus, it is important to have optimal in vitro conditions, avoiding the presence of other pathogens that can alter the results. BVDV is one of the most frequent viral contaminants of cell cultures. Considering that non-cytopathic (NCP) BVDV biotype can generate persistently infected (PI) cattle, which are the major source for virus transmission in susceptible herds, it is important to check products derived from cattle that are intended to be used in research laboratories. The aim of this work was to evaluate how the natural infection of bovine endometrial cells (BEC) with a NCP BVDV strain (BEC + BVDV) affects BoHV-4 replication. We have demonstrated a delay in BoHV-4 gene expression and a decrease in viral load in the extracellular environment in BEC + BDVD cells compared to BEC (BVDV-free) cells. These results confirm that replication of BoHV-4 in BEC primary cultures is affected by previous infection with BVDV. This finding highlights the importance of ruling out BVDV infection in bovine primary cell cultures to avoid biological interference or misinterpretation of results at the time of performing in vitro studies with BoHV-4.

Gene expression and in vitro replication of bovine gammaherpesvirus type 4.

In vitro cell cultures are widely used models for dissecting cellular and molecular mechanisms that lead to certain physiological conditions and diseases. The pathogenesis of BoHV-4 in the bovine reproductive tract has been studied by conducting tests on primary cultures. However, many questions remain to be answered about the role of BoHV-4 in endometrial cells. The aim of this study was to compare the replication and gene expression of BoHV-4 in cell lines and bovine reproductive tract primary cells as an in vitro model for the study of this virus. We demonstrated that BoHV-4 strains differ in their in vitro growth kinetics and gene expression but have the same cell type preference. Our results demonstrate that BoHV-4 replicates preferentially in bovine endometrial cells (BEC). However, its replication capacity extends to various cell types, since all cells that were tested were permissive to BoHV-4 infection. The highest virus titers were obtained in BEC cells. Nevertheless, virus replication efficiency could not be fully predicted from the mRNA expression profiles. This implies that there are multiple cell-type-dependent factors and strain properties that determine the level of BoHV-4 replication. The results of this study provide relevant information about the in vitro behavior of two field isolates of BoHV-4 in different cell cultures. These findings may be useful for the design of future in vitro experiments to obtain reliable results not only about the pathogenic role of BoHV-4 in the bovine female reproductive tract but also in the development of efficient antiviral strategies.

Acute Kidney Injury After Cardiac Transplantation: Foe or Common Innocent Bystander?

BACKGROUND: Heart transplantation (HT) is regarded as the treatment of choice for end-stage heart failure (ESHF) patients. Severe acute kidney injury (AKI) after HT is a frequent clinical problem with devastating consequences for HT recipients. METHODS: Data from 112 ESHF patients undergoing HT in 2010-2015 were retrospectively reviewed. The primary end point was the development of AKI stage III, and secondary outcomes were in-hospital and 1-year mortality according to Kidney Disease Improving Global Outcomes criteria. RESULTS: In total, 81 patients (72.3%) developed AKI, of which 33 (29.4%) developed AKI stage I, 18 (16%) stage II, and 30 (26.7%) stage III; within this group, 27 recipients (24%) required renal replacement therapy (RRT). Overall hospital mortality was 14%. However, when stratifying by AKI stage, hospital mortality increased from 0% to 46% comparing recipients without AKI and those with AKI stage III, respectively (P = .001). In the same way, 1-year mortality increased from 6% to 53% for recipients without AKI compared with those who developed AKI stage III (log-rank test for trend: P = .001). Recipients that required RRT had a 1-year mortality of 59.2% compared with 5.8% in those without RRT requirement. CONCLUSIONS: The findings indicate that AKI stage III is common after HT and adversely affects early and late mortality. Clinical variables together with perioperative hemodynamic assessment could add more powerful prognostic information to predict severe AKI before HT and therefore evaluate potential heart-kidney recipients.