Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.

Objective: Correct and timely identification of SARS-CoV-2-positive patients is critical in the emergency department (ED) prior to admission to medical wards. Antigen-detecting rapid diagnostic tests (Ag-RDTs) are a rapid alternative to Reverse-transcriptase polymerase chain reaction (RT-PCR) for the diagnosis of COVID-19 but have lower sensitivity. Methods: We evaluated the performance in real-life conditions of a strategy combining Ag-RDT and chest computed tomography (CT) to rule out COVID-19 infection in 1015 patients presenting in the ED between 16 November 2020 and 18 January 2021 in order to allow non-COVID-19 patients to be hospitalized in dedicated units directly. The combined strategy performed in the ED for patients with COVID-19 symptoms was assessed and compared with RT-PCR. Results: Compared with RT-PCR, the negative predictive value was 96.7% for Ag-RDT alone, 98.5% for Ag-RDT/CT combined, and increased to 100% for patients with low viral load. Conclusion: A strategy combining Ag-RDT and chest CT is effective in ruling out COVID-19 in ED patients with high precision.