scholarly journals Author response: Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture

2016 ◽  
Author(s):  
Katherine S Xue ◽  
Kathryn A Hooper ◽  
Anja R Ollodart ◽  
Adam S Dingens ◽  
Jesse D Bloom
2002 ◽  
Vol 46 (4) ◽  
pp. 1014-1021 ◽  
Author(s):  
Warren M. Kati ◽  
Debra Montgomery ◽  
Robert Carrick ◽  
Larisa Gubareva ◽  
Clarence Maring ◽  
...  

ABSTRACT A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (Ki ) values between 0.024 and 0.31 nM. These values were comparable to or lower than the Ki values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections.


2016 ◽  
Author(s):  
Siming Ma ◽  
Akhil Upneja ◽  
Andrzej Galecki ◽  
Yi-Miau Tsai ◽  
Charles F Burant ◽  
...  

2018 ◽  
Vol 115 (35) ◽  
pp. E8276-E8285 ◽  
Author(s):  
Juhye M. Lee ◽  
John Huddleston ◽  
Michael B. Doud ◽  
Kathryn A. Hooper ◽  
Nicholas C. Wu ◽  
...  

Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.


2020 ◽  
Author(s):  
Shahana Begum ◽  
Mohammed Nooruzzaman ◽  
Azmary Hasnat ◽  
Mst. Murshida Parvin ◽  
Rokshana Parvin ◽  
...  

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Katherine S Xue ◽  
Kathryn A Hooper ◽  
Anja R Ollodart ◽  
Adam S Dingens ◽  
Jesse D Bloom

RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.


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