Rescue of a H3N2 Influenza Virus Containing a Deficient Neuraminidase Protein by a Hemagglutinin with a Low Receptor-Binding Affinity

Influenza viruses possess at their surface two glycoproteins, the hemagglutinin and the neuraminidase, of which the antagonistic functions have to be well balanced for the virus to grow efficiently. Ferraris et al. isolated in 2003–2004 viruses lacking both a NA gene and protein (H3NA- viruses) (Ferraris O., 2006, Vaccine, 24(44–46):6656-9). In this study we showed that the hemagglutinins of two of the H3NA- viruses have reduced affinity for SAα2.6Gal receptors, between 49 and 128 times lower than that of the A/Moscow/10/99 (H3N2) virus and no detectable affinity for SAα2.3Gal receptors. We also showed that the low hemagglutinin affinity of the H3NA- viruses compensates for the lack of NA activity and allows the restoration of the growth of an A/Moscow/10/99 virus deficient in neuraminidase. These observations increase our understanding of H3NA- viruses in relation to the balance between the functional activities of the neuraminidase and hemagglutinin

Combinatorial effect of two framework mutations (E119V and I222L) in the neuraminidase active site of H3N2 influenza virus on resistance to oseltamivir

Neuraminidase (NA) inhibitors (NIs) are the first line of defense against influenza virus. Reverse genetics experiments allow the study of resistance mechanisms by anticipating the impacts of mutations to the virus. To look at the possibility of an increased effect on the resistance phenotype of a combination of framework mutations, known to confer resistance to oseltamivir or zanamivir, with limited effect on virus fitness, we constructed 4 viruses by reverse genetics in the A/Moscow/10/99 H3N2 background containing double mutations in their neuraminidase genes: E119D+I222L, E119V+I222L, D198N+I222L, and H274Y+I222L (N2 numbering). Among the viruses produced, the E119D+I222L mutant virus was not able to grow without bacterial NA complementation and the D198N+I222L mutant and H274Y+I222L mutant were not stable after passages in MDCK cells. The E119V+I222L mutant was stable after five passages in MDCK cells. This E119V-and-I222L combination had a combinatorial effect on oseltamivir resistance. The total NA activity of the E119V+I222L mutant was low (5% compared to that of the wild-type virus). This drop in NA activity resulted from a decreased NA quantity in the virion in comparison to that of the wild-type virus (1.4% of that of the wild type). In MDCK-SIAT1 cells, the E119V+I222L mutant virus did not present a replicative advantage over the wild-type virus, even in the presence of oseltamivir. Double mutations combining two framework mutations in the NA gene still have to be monitored, as they could induce a high level of resistance to NIs, without impairing the NA affinity. Our study allows a better understanding of the diversity of the mechanisms of resistance to NIs

Influenza viruses production: Evaluation of a novel avian cell line DuckCelt (R)-T17

SSCI-VIDE+CARE+FDA:CGUInternational audienceAvian cell lin

Antenatal presentation of hereditary lymphedema type I.

Fetal edema can present as limited subcutaneous edema, fluid accumulation in body cavities or hydrops fetalis. Hydrops fetalis is the end stage of a variety of fetal/maternal disorders and nonimmune etiology represents more than 3/4 of cases. Lymphatic dysplasia may account for a subset of patients with nonimmune and "idiopathic" hydrops fetalis, fetal chylous ascites or chylothorax. We present two unrelated patients with antenatal features of hereditary lymphedema syndrome, in whom Milroy disease was diagnosed after birth. At least, 20 genes have been identified to cause primary lymphedema, with sometimes antenatal features. Hereditary lymphedema syndrome should be considered in cases of nonimmune hydrops fetalis/fetal edema after ruling out the more common etiologies

Role of interfering substances in the survival of coronaviruses on surfaces and their impact on the efficiency of hand and surface disinfection

AbstractContaminated environmental surfaces are considered to represent a significant vector for hospital-acquired viral infections. In this study, we have evaluated the impact of interfering substances on SARS-CoV-2 surface stability and virucidal efficiency of hand sanitizers and surface disinfectant. To this end, surface stability of SARS-CoV-2 was measured on stainless steel in different experimental conditions, with or without an artificial mucus/saliva mixture and compared against that of human coronavirus HCoV-229E and feline coronavirus FCoV. The impact of the mucus/saliva mixture on the virucidal efficiency of 3 commercial alcohol hand sanitizers and 1 surface chemical disinfectant against SARS-CoV-2, HCoV-229E and FCoV was then measured. Our results indicate that mucus/saliva mixture did not demonstrate a beneficial effect on the surface survival of tested viruses, with temperature being an important parameter. In addition, we demonstrated that interfering substances may play an important role in the virucidal efficacy of hand sanitizers and disinfectants, highlighting the need for adapted testing protocols that better reflect current “real life” conditions of use.HighlightsContaminated environmental surfaces are a significant vector for viral infections.We studied the impact of interfering substances on SARS-CoV-2 surface stability and virucidal efficiency.Mucus/saliva did not demonstrate a beneficial effect on viral surface stability, with temperature being an important parameter.Interfering substances are important for virucidal surface activity of disinfectants.</jats:sec