scholarly journals Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Iebe Rossey ◽  
Morgan S. A. Gilman ◽  
Stephanie C. Kabeche ◽  
Koen Sedeyn ◽  
Daniel Wrapp ◽  
...  

Abstract Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.

1970 ◽  
Vol 68 (4) ◽  
pp. 581-588 ◽  
Author(s):  
R. Scott ◽  
P. S. Gardner

SUMMARYNasopharyngeal secretions were taken during the acute phase of illness from 30 children admitted to hospital with lower respiratory tract infections. The presence of neutralizing activity in secretions taken at the onset of illness was demonstrated in 11 out of 15 patients (73%) with bronchiolitis caused by R.S. virus, as compared with 4 out of 9 patients (44%) with R.S. virus infections other than bronchiolitis, and 1 out of 6 without R.S. virus infection. Second secretions were taken 7 days later from 10 of the children with R.S. virus infection. Eight of these paired secretions showed an increase of neutralizing activity against R.S. virus. It is suggested that the neutralizing activity, found in secretions taken at the onset of illness, may be a result of previous infection with R.S. virus.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Iebe Rossey ◽  
Morgan S. A. Gilman ◽  
Stephanie C. Kabeche ◽  
Koen Sedeyn ◽  
Daniel Wrapp ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rafik Dey ◽  
Melanie A. Folkins ◽  
Nicholas J. Ashbolt

AbstractHuman respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and immunocompromised adults worldwide. Here we report that amoebae-release respirable-sized vesicles containing high concentrations of infectious RSV that persisted for the duration of the experiment. Given the ubiquity of amoebae in moist environments, our results suggest that extracellular amoebal-vesicles could contribute to the environmental persistence of respiratory viruses, including potential resistance to disinfection processes and thereby offering novel pathways for viral dissemination and transmission.


2019 ◽  
Vol 113 (8) ◽  
pp. 446-452
Author(s):  
Damilola M Oladele ◽  
Dimeji P Oladele ◽  
Rasheedat M Ibraheem ◽  
Mohammed B Abdulkadir ◽  
Rasaki Adewole Raheem ◽  
...  

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Juan Carlos Muñoz-Escalante ◽  
Andreu Comas-García ◽  
Sofía Bernal-Silva ◽  
Carla Daniela Robles-Espinoza ◽  
Guillermo Gómez-Leal ◽  
...  

AbstractRespiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.


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