In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation

CMV associated tissue-invasive disease is associated with a considerable risk of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recently, the terminase inhibitor letermovir (LMV) has been approved for prophylaxis of CMV infection in HSCT. We hereby report a 60-year-old female experiencing CMV reactivation after HSCT in a CMV seronegative donor-constellation. Due to ongoing elevated CMV viral load and drug-associated myelosuppression, which prevented ganciclovir therapy, treatment was replaced by foscarnet. Due to nephrotoxicity, foscarnet was switched to LMV. The patient developed skin GvHD and prednisolone was started. Subsequently, CMV viremia worsened despite LMV therapy. Genotyping revealed the mutation C325Y of the CMV UL56 terminase being associated with high-level resistance against LMV. Prolonged uncontrolled low-level viremia due to prednisolone treatment may have favored the selection of drug-resistant CMV. Despite the excellent toxicity profile of LMV, physicians should be aware of risk factors for the emergence of resistance

Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi‐taxa and multi‐scale approach

Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turno-ver of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the en-vironmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size.Location: Temperate forests in five regions across Germany.Methods: In the inter-region analysis, the independent and shared effects of the re-gional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined.Results: In the inter-region analysis, over half of the explained variation in community composition (23% of the total explained 35%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less disper-sive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physi-ognomy, but the relative importance of the latter increased with increasing trophic position and body size.Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conserva-tion frameworks targeting biodiversity of multiple groups should cover both envi-ronmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy

Heterogeneity–diversity relationships differ between and within trophic levels in temperate forests

The habitat heterogeneity hypothesis predicts that biodiversity increases with increasing habitat heterogeneity due to greater niche dimensionality. However, recent studies have reported that richness can decrease with high heterogeneity due to stochastic extinctions, creating trade-offs between area and heterogeneity. This suggests that greater complexity in heterogeneity–diversity relationships (HDRs) may exist, with potential for group-specific responses to different facets of heterogeneity that may only be partitioned out by a simultaneous test of HDRs of several species groups and several facets of heterogeneity. Here, we systematically decompose habitat heterogeneity into six major facets on ~500 temperate forest plots across Germany and quantify biodiversity of 12 different species groups, including bats, birds, arthropods, fungi, lichens and plants, representing 2,600 species. Heterogeneity in horizontal and vertical forest structure underpinned most HDRs, followed by plant diversity, deadwood and topographic heterogeneity, but the relative importance varied even within the same trophic level. Among substantial HDRs, 53% increased monotonically, consistent with the classical habitat heterogeneity hypothesis but 21% were hump-shaped, 25% had a monotonically decreasing slope and 1% showed no clear pattern. Overall, we found no evidence of a single generalizable mechanism determining HDR patterns