scholarly journals Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New South Wales, Australia

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 476 ◽  
Author(s):  
Francesca Di Giallonardo ◽  
Jen Kok ◽  
Marian Fernandez ◽  
Ian Carter ◽  
Jemma Geoghegan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
New South ◽  
New South Wales ◽  
Host Population ◽  
Human Respiratory Syncytial Virus ◽  
Nucleotide Substitutions ◽  
South Wales ◽  
A Genome ◽  
Syncytial Virus ◽  
Tract Infections

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is a major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of the genetic diversity of RSV in Australia, nor the factors that shape this diversity. We have conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010–2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6–8 × 10−4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year and only limited evidence for multi-year persistence.

scholarly journals Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New South Wales, Australia

2018 ◽  
Author(s):  
Francesca Di Giallonardo ◽  
Jen Kok ◽  
Marian Fernandez ◽  
Ian Carter ◽  
Jemma L. Geoghegan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
New South ◽  
New South Wales ◽  
Host Population ◽  
Human Respiratory Syncytial Virus ◽  
Nucleotide Substitutions ◽  
South Wales ◽  
A Genome ◽  
Syncytial Virus ◽  
Tract Infections

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.

scholarly journals Respiratory Syncytial Virus-Attributable Deaths in a Major Pediatric Hospital in New South Wales, Australia, 1998–2018

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Gemma L. Saravanos ◽  
Peter Hsu ◽  
David Isaacs ◽  
Kristine Macartney ◽  
Nicholas J. Wood ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
New South ◽  
New South Wales ◽  
Pediatric Hospital ◽  
South Wales ◽  
Syncytial Virus

scholarly journals Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

2021 ◽  
Vol 9 (6) ◽  
pp. 1293
Author(s):  
Gaspar A. Pacheco ◽  
Nicolás M. S. Gálvez ◽  
Jorge A. Soto ◽  
Catalina A. Andrade ◽  
Alexis M. Kalergis
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogens ◽  
Parainfluenza Viruses ◽  
Starting Point ◽  
The Social ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

scholarly journals Genetic Variability and Molecular Evolution of the Human Respiratory Syncytial Virus Subgroup B Attachment G Protein

2005 ◽  
Vol 79 (14) ◽  
pp. 9157-9167 ◽  
Author(s):  
Kalina T. Zlateva ◽  
Philippe Lemey ◽  
Elien Moës ◽  
Anne-Mieke Vandamme ◽  
Marc Van Ranst
Keyword(s):  
Respiratory Syncytial Virus ◽  
Genetic Variability ◽  
G Protein ◽  
Antigenic Variation ◽  
Human Respiratory Syncytial Virus ◽  
Recent Common Ancestor ◽  
Nucleotide Substitutions ◽  
Host Immune Responses ◽  
Most Recent Common Ancestor ◽  
Syncytial Virus

ABSTRACT Human respiratory syncytial virus (HRSV) is the most important cause of acute respiratory disease in infants. Two major subgroups (A and B) have been identified based on antigenic differences in the attachment G protein. Antigenic variation between and within the subgroups may contribute to reinfections with these viruses by evading the host immune responses. To investigate the circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed the G protein genetic variability of subgroup B sequences isolated over a 45-year period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to 2004). Our study revealed that the HRSV-B evolutionary rate (1.95 × 10−3 nucleotide substitutions/site/year) is similar to that previously estimated for HRSV-A (1.83 × 10−3 nucleotide substitutions/site/year). However, natural HRSV-B isolates appear to accommodate more drastic changes in their attachment G proteins. The most recent common ancestor of the currently circulating subgroup B strains was estimated to date back to around the year 1949. The divergence between the two major subgroups was calculated to have occurred approximately 350 years ago. Furthermore, we have identified 12 positively selected sites in the G protein ectodomain, suggesting that immune-driven selective pressure operates in certain codon positions. HRSV-A and -B strains have similar phylodynamic patterns: both subgroups are characterized by global spatiotemporal strain dynamics, where the high infectiousness of HRSV permits the rapid geographic spread of novel strain variants.

scholarly journals Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and genetic stability without loss of attenuation

2021 ◽  
Vol 17 (12) ◽  
pp. e1010191
Author(s):  
Jessica W. Chen ◽  
Lijuan Yang ◽  
Celia Santos ◽  
Sergio A. Hassan ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Temperature Sensitivity ◽  
Genetic Stability ◽  
Large Scale ◽  
Selective Pressure ◽  
Human Respiratory Syncytial Virus ◽  
Nucleotide Substitutions ◽  
Functional Efficiency ◽  
Codon Pair ◽  
Syncytial Virus

Recoding viral genomes by introducing numerous synonymous nucleotide substitutions that create suboptimal codon pairs provides new live-attenuated vaccine candidates. Because recoding typically involves a large number of nucleotide substitutions, the risk of de-attenuation is presumed to be low. However, this has not been thoroughly studied. We previously generated human respiratory syncytial virus (RSV) in which the NS1, NS2, N, P, M and SH ORFs were codon-pair deoptimized (CPD) by 695 synonymous nucleotide changes (Min A virus). Min A exhibited a global reduction in transcription and protein synthesis, was restricted for replication in vitro and in vivo, and exhibited moderate temperature sensitivity. Here, we show that under selective pressure by serial passage at progressively increasing temperatures, Min A regained replication fitness and lost its temperature sensitivity. Whole-genome deep sequencing identified numerous missense mutations in several genes, in particular ones accumulating between codons 25 and 34 of the phosphoprotein (P), a polymerase cofactor and chaperone. When re-introduced into Min A, these P mutations restored viral transcription to wt level, resulting in increased protein expression and RNA replication. Molecular dynamic simulations suggested that these P mutations increased the flexibility of the N-terminal domain of P, which might facilitate its interaction with the nucleoprotein N, and increase the functional efficiency of the RSV transcription/replication complex. Finally, we evaluated the effect of the P mutations on Min A replication and immunogenicity in hamsters. Mutation P[F28V] paradoxically reduced Min A replication but not its immunogenicity. The further addition of one missense mutation each in M and L generated a version of Min A with increased genetic stability. Thus, this study provides further insight into the adaptability of large-scale recoded RNA viruses under selective pressure and identified an improved CPD RSV vaccine candidate.

scholarly journals TMEM16A/ANO1 calcium-activated chloride channel as a novel target for the treatment of human respiratory syncytial virus infection

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 64-72
Author(s):  
Hayley Pearson ◽  
Eleanor J A A Todd ◽  
Mareike Ahrends ◽  
Samantha E Hover ◽  
Adrian Whitehouse ◽  
...  
Keyword(s):  
Life Cycle ◽  
Respiratory Syncytial Virus ◽  
Human Lung ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogen ◽  
Human Lung Epithelial Cell ◽  
Syncytial Virus ◽  
Tract Infections

IntroductionHuman respiratory syncytial virus (HRSV) is a common cause of respiratory tract infections (RTIs) globally and is one of the most fatal infectious diseases for infants in developing countries. Of those infected, 25%–40% aged ≤1 year develop severe lower RTIs leading to pneumonia and bronchiolitis, with ~10% requiring hospitalisation. Evidence also suggests that HRSV infection early in life is a major cause of adult asthma. There is no HRSV vaccine, and the only clinically approved treatment is immunoprophylaxis that is expensive and only moderately effective. New anti-HRSV therapeutic strategies are therefore urgently required.MethodsIt is now established that viruses require cellular ion channel functionality to infect cells. Here, we infected human lung epithelial cell lines and ex vivo human lung slices with HRSV in the presence of a defined panel of chloride (Cl−) channel modulators to investigate their role during the HRSV life-cycle.ResultsWe demonstrate the requirement for TMEM16A, a calcium-activated Cl− channel, for HRSV infection. Time-of-addition assays revealed that the TMEM16A blockers inhibit HRSV at a postentry stage of the virus life-cycle, showing activity as a postexposure prophylaxis. Another important negative-sense RNA respiratory pathogen influenza virus was also inhibited by the TMEM16A-specific inhibitor T16Ainh-A01.DiscussionThese findings reveal TMEM16A as an exciting target for future host-directed antiviral therapeutics.

Sign in / Sign up

Export Citation Format

Share Document