Spectrum of adult Parvovirus B19 infection according to the underlying predisposing condition and proposals for clinical practice.

The virological diagnosis of Parvovirus B19 (PvB19) infection is currently based on sero-diagnosis, molecular methods or both, yet without clear recommendations. We retrospectively identified patients with polymerase chain reaction-positive PvB19 and/or positive serological assay between 2007 and 2013. Eighty-two adults with at least one diagnostic criterion of recent PvB19 infection (IgM antibodies, viral DNA in blood and/or in marrow) were included and classified into three homogeneous groups: 30 patients had no underlying predisposing condition, 25 a hereditary haemolytic anaemia, 27 an underlying immunodeficiency. The classical PvB19-related manifestations were less frequent in immunocompromised than in immunocompetent patients (arthromyalgia: 5 vs. 14; erythema: 4 vs. 17, respectively). Only 41·4% of patients with no underlying disease were anaemic. Bicytopenia and pancytopenia were observed mainly in immunocompromised patients. Classical pure red cell aplasia was observed in only 9 of the 27 marrow smears performed. Specific IgM were found in 93% of immunocompetent patients, whereas only 58% had detectable viral DNA in blood. IgM and DNA were present alone or together in all patients with hereditary haemolytic anaemia. In immunocompromised patients, the diagnosis was confirmed by marrow analysis in 91% of cases. We make some proposals based on this large series of PvB19-infected patients.

Higher-order interfiber interactions in the self-assembly of benzene-1,3,5-tricarboxamide-based peptides in water.

Mimicking the complexity of biological systems with synthetic supramolecular materials requires a deep understanding of the relationship between the structure of the molecule and its self-assembly pattern. Herein, we report a series of water-soluble benzene-1,3,5-tricarboxamide-based di- and tripeptide derivatives modified with small non-bulky terminal amine salt to induce self-assembly into twisted one-dimensional higher-order nanofibers. The morphology of nanofibers strongly depends on the nature, order, and quantity of amino acids in the short peptide fragments and vary from simple cylindrical to complex helical. From observations of several fiber-splitting events, we detected interfiber interactions that always occur in a pairwise manner, which implies that the C3 symmetry of benzene-1,3,5-tricarboxamide-based molecules in higher-order fibers becomes gradually distorted, thus facilitating hydrophobic contact interactions between fibrils. The proposed mechanism of self-assembly through hydrophobic contact allowed the successful design of a compound with pH-responsive morphology, and may find use in the future development of complex hierarchical architectures with controlled functionality.

Characterization of the dynamics of human cytomegalovirus resistance to antiviral drugs by ultra-deep sequencing.

Prophylactic or preemptive treatment strategies are required to prevent human cytomegalovirus (CMV) infections in transplant recipients. However, treatment failure occurs when CMV resistant-associated variants (RAVs) are selected. Although the diversity of CMV is lower than that of RNA viruses, CMV appears to show some genetic instability, with possible minor emerging resistance that may be undetectable by Sanger sequencing. We aimed to examine CMV-resistance mutations over time by ultra-deep sequencing (UDS) and Sanger sequencing in a kidney transplant recipient experiencing CMV infection. This patient showed a transient response to three different antiviral drugs (valganciclovir, foscarnet, and maribavir) and four episodes of CMV resistance over two years. The full-length UL97 (2.3kpb) and partial UL54 (2.4kpb) CMV genes were studied by UDS and Sanger sequencing and linkage mutations calculated to determine RAVs. We detected four major and five minor resistance mutations. Minor resistant variants (2-20%) were detected by UDS, whereas major resistance substitutions (>20%) were identified by both UDS and Sanger method. We detected cross-resistance to three drugs, despite high CMV loads, suggesting that the fitness of the viral mutants was not impaired. In conclusion, CMV showed complex dynamic of resistance under antiviral drug pressure, as described for highly variable viruses. The emergence of successive RAVs constitutes a clinically challenging complication and contributes to the difficulty of therapeutic management of patients.