Controversy on Virus Designation: Alkhumra Sive Alkhurma Hemorrhagic Fever Flavivirus

Intervirology has decided to publish the ensuing letter by Madani et al. [1] and a response by Alzahrani et al. [2] concerning a prior publication [3] . As the letter by Madani et al. was obviously not accepted by EID, Intervirology feels that it is fair and appropriate to provide the authors the opportunity to discuss what they see as substantial errors in the work of Alzahrani et al. [3] . Taxonomy is apparently a matter that raises emotions. Disagreements between researchers on designation of a new virus have occurred in the past, one only has to remember the issue on HTLV-III versus LAV between renowned groups of researches that was eventually cleared

Human Rhinoviruses in Adult Patients in a Tertiary Care Hospital in Germany: Molecular Epidemiology and Clinical Significance

Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in adult patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and the partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of adult RV infections. In total, the respiratory specimens of 284 adult patients (18–90 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed a remarkably high intra- and interseasonal diversity of RV genotypes. RV species were detected in the following ratios: 60.9% RV-A 173, 12.7% RV-B, and 26.4% RV-C. No correlations between RV species and underlying comorbidities such as asthma (p = 0.167), COPD (p = 0.312) or immunosuppression (p = 0.824) were found. However, 21.1% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p = 0.024), LRTI (p < 0.001), and pneumonia (p = 0.01). Taken together, this study shows a pronounced genetic diversity of RV in adults and underlines the important role of co-infections. No correlation of specific RV species with a particular clinical presentation could be deduced

Human Rhinoviruses in Pediatric Patients in a Tertiary Care Hospital in Germany: Molecular Epidemiology and Clinical Significance

Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of pediatric RV infections. In total, the respiratory specimens of 776 patients (<18 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed remarkably high intra- and interseasonal diversity for RV genotypes. RV species were detected in the following frequencies: 49.1% RV-A, 5.9% RV-B, and 43.6% RV-C. RV-C was found to be more frequently associated with asthma (p = 0.04) and bronchiolitis (p < 0.001), while RV-A was more frequently associated with fever (p = 0.001) and pneumonia (p = 0.002). Additionally, 35.3% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p < 0.001), need for ventilation (p < 0.001), and pneumonia (p < 0.001). Taken together, this study shows pronounced RV genetic diversity in pediatric patients and indicates differences in RV-associated pathologies, as well as an important role for co-infections

Dual Promoters Improve the Rescue of Recombinant Measles Virus in Human Cells

Reverse genetics is a technology that allows the production of a virus from its complementary DNA (cDNA). It is a powerful tool for analyzing viral genes, the development of novel vaccines, and gene delivery vectors. The standard reverse genetics protocols are laborious, time-consuming, and inefficient for negative-strand RNA viruses. A new reverse genetics platform was established, which increases the recovery efficiency of the measles virus (MV) in human 293-3-46 cells. The novel features compared with the standard system involving 293-3-46 cells comprise (a) dual promoters containing the RNA polymerase II promoter (CMV) and the bacteriophage T7 promoter placed in uni-direction on the same plasmid to enhance RNA transcription; (b) three G nucleotides added just after the T7 promoter to increase the T7 RNA polymerase activity; and (c) two ribozymes, the hairpin hammerhead ribozyme (HHRz), and the hepatitis delta virus ribozyme (HDVrz), were used to cleavage the exact termini of the antigenome RNA. Full-length antigenome cDNA of MV of the wild type IC323 strain or the vaccine AIK-C strain was inserted into the plasmid backbone. Both virus strains were easily rescued from their respective cloned cDNA. The rescue efficiency increased up to 80% compared with the use of the standard T7 rescue system. We assume that this system might be helpful in the rescue of other human mononegavirales

Photodynamic inactivation of SARS-CoV-2 infectivity and antiviral treatment effects in vitro

Despite available vaccines, antibodies and antiviral agents, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic still continues to cause severe disease and death. Current treatment options are limited, and emerging new mutations are a challenge. Thus, novel treatments and measures for prevention of viral infections are urgently required. Photodynamic inactivation (PDI) is a potential treatment for infections by a broad variety of critical pathogens, including viruses. We explored the infectiousness of clinical SARS-CoV-2 isolates in Vero cell cultures after PDI-treatment, using the photosensitizer Tetrahydroporphyrin-tetratosylate (THPTS) and near-infrared light. Replication of viral RNA (qPCR), viral cytopathic effects (microscopy) and mitochondrial activity were assessed. PDI of virus suspension with 1 µM THPTS before infection resulted in a reduction of detectable viral RNA by 3 log levels at day 3 and 6 after infection to similar levels as in previously heat-inactivated virions (<99.9%; p < 0.05). Mitochondrial activity, which was significantly reduced by viral infection, was markedly increased by PDI to levels similar to uninfected cell cultures. When applying THPTS-based PDI after infection, a single treatment had a virus load-reducing effect only at a higher concentration (3 µM) and reduced cell viability in terms of PDI-induced toxicity. Repeated PDI with 0.3 µM THPTS every 4 h for 3 d after infection reduced the viral load by more than 99.9% (p < 0.05), while cell viability was maintained. Our data demonstrate that THPTS-based antiviral PDI might constitute a promising approach for inactivation of SARS-CoV-2. Further testing will demonstrate if THPTS is also suitable to reduce the viral load in vivo

Highly Elevated Serum Hepcidin in Patients with Acute Myeloid Leukemia prior to and after Allogeneic Hematopoietic Cell Transplantation: Does This Protect from Excessive Parenchymal Iron Loading?

Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre- and post-HCT was present in all patients. Median hepcidin pre- and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P<.0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P<.0005), pre- and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P=.001) and hepcidin (P=.001). No correlation of pre- or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre- and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT

Highly Elevated Serum Hepcidin in Patients with Acute Myeloid Leukemia prior to and after Allogeneic Hematopoietic Cell Transplantation: Does This Protect from Excessive Parenchymal Iron Loading?

Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre-and post-HCT was present in all patients. Median hepcidin pre-and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P &lt; .0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P &lt; .0005), pre-and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P = .001) and hepcidin (P = .001). No correlation of pre-or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre-and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT

Controversy on Virus Designation: Alkhumra Sive Alkhurma Hemorrhagic Fever Flavivirus

Intervirology has decided to publish the ensuing letter by Madani et al. [1] and a response by Alzahrani et al. [2] concerning a prior publication [3] . As the letter by Madani et al. was obviously not accepted by EID, Intervirology feels that it is fair and appropriate to provide the authors the opportunity to discuss what they see as substantial errors in the work of Alzahrani et al. [3] . Taxonomy is apparently a matter that raises emotions. Disagreements between researchers on designation of a new virus have occurred in the past, one only has to remember the issue on HTLV-III versus LAV between renowned groups of researches that was eventually cleared

Controversy on Virus Designation: Alkhumra Sive Alkhurma Hemorrhagic Fever Flavivirus

Intervirology has decided to publish the ensuing letter by Madani et al. [1] and a response by Alzahrani et al. [2] concerning a prior publication [3] . As the letter by Madani et al. was obviously not accepted by EID, Intervirology feels that it is fair and appropriate to provide the authors the opportunity to discuss what they see as substantial errors in the work of Alzahrani et al. [3] . Taxonomy is apparently a matter that raises emotions. Disagreements between researchers on designation of a new virus have occurred in the past, one only has to remember the issue on HTLV-III versus LAV between renowned groups of researches that was eventually cleared