Characterization of host cell binding variants of influenza virus by monoclonal antibodies

Nohinek, B.; Gerhard, Walter; Schulze, Irene T.

doi:10.1016/0042-6822(85)90407-6

Cited by 16 publications

(15 citation statements)

References 14 publications

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“…Preparation and assay of viruses. The viruses used in this study are all variants of the WSN strain of influenza A (H1N1) virus which we have previously characterized (5,8,19,20). Their properties are summarized in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Single amino acid substitutions in the hemagglutinin can alter the host range and receptor binding properties of H1 strains of influenza A virus

Aytay

Schulze

1991

J Virol

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We have previously characterized an influenza A (HlNl) virus which has host-dependent growth and receptor binding properties and have shown that a mutation which removes an oligosaccharide from the tip of the hemagglutinin (HA) by changing Asn-129 to Asp permits this virus to grow to high titer in MDBK cells. (C. M. Deom, A. J. Caton, and I. T. Schulze, Proc. Natl. Acad. Sci. USA 83:3771-3775, 1986). We have now isolated monoclonal antibodies specific for the mutant HA and have used escape mutants to identify alterations in HA sequence which reduce virus yields from MDBK cells without reducing those from chicken embryo fibroblasts. Two types of escape mutants which grow equally well in chicken embryo fibroblasts were obtained. Those with the parent phenotype contain Asn at residue 129 and are glycosylated at that site. Those with the mutant phenotype are unchanged at residue 129 but have a Gly to Glu substitution at residue 158, which is close to residue 129 on the HAl subunit. Binding assays with neoglycoproteins containing N-acetylneuraminic acid in either a2,3 or at2,6 linkage to galactose showed that the MDBK-synthesized oligosaccharides at Asn-129 reduce binding to both of these receptors, leaving the HA's preference for a2,6 linkages unchanged. Glu at residue 158 greatly reduces binding to both receptors without reducing virus yields from MDBK cells. We conclude that changes in the receptor binding properties of the HA can result either from direct alteration of the HA protein by host cell glycosylation or from mutations in the HA gene and that these changes generate heterogeneity that can contribute to the survival of influenza A virus populations in nature.

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Section: Methodsmentioning

confidence: 99%

Single amino acid substitutions in the hemagglutinin can alter the host range and receptor binding properties of H1 strains of influenza A virus

Aytay

Schulze

1991

J Virol

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“…MDBK cells and primary CEF were grown as described (1). Stocks of the parent and mutant strains of influenza A/WSN (HlNl) virus, grown in CEF, were prepared as described (2).…”

Section: Methodsmentioning

confidence: 99%

“…This mutation also makes the mutant virus more resistant than the parental virus to neutralization by certain monoclonal antibodies (2). These observations were made by comparing the biological properties of a spontaneous mutant of the WSN strain of influenza virus with those of the parental virus.…”

Section: Introductionmentioning

confidence: 99%

Host cell-mediated selection of a mutant influenza A virus that has lost a complex oligosaccharide from the tip of the hemagglutinin.

Deom¹,

Caton²,

Schulze³

1986

Proc. Natl. Acad. Sci. U.S.A.

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We have now compared the hemagglutinin (HA) subunits, HA1 and HA2, of the parent and mutant viruses by NaDodSO4/PAGE and have found that when the viruses are grown in either host cell the HA1 subunit of the mutant is smaller than that of the parent virus. The nonglycosylated HAs, made in the presence of tunicamycin, have the same apparent molecular weight, indicating that the HA1 subunit of the mutant virus contains less carbohydrate than that of the parent. This reduction in carbohydrate content was observed with 11 independently derived mutants that had been selected by growth in MDBK cells. The nucleotide sequence of the HA gene of the parent and mutant viruses indicates that there are five potential glycosylation sites on the parent HA1 subunit and four on the mutant and that the mutation responsible for this difference is a single base change that eliminates the glycosylation site at amino acid 125 of the parent HA1 subunit. Treatment of the parent and mutant HAs from both cell sources with endo-f3-N-acetylglucosaminidases F and H showed that the HA1 of the parent virus has four complex and one high-mannose oligosaccharides, whereas that of the mutant virus has three complex and one highmannose oligosaccharides. Thus, all of the potential sites on both HA1 subunits are glycosylated. We conclude that the oligosaccharide attached to amino acid 125 of the parent HA by MDBK cells can reduce the affinity of the virus for cellular receptors and that the mutant virus has a higher affminty than the parent because the mutant HA is not glycosylated at that site. Since amino acid 125 of the parent HA is glycosylated by both CEF and MDBK cells, we further conclude that the host-determined structure of the oligosaccharide at that site affects the affinity ofthe parent virus for cellular receptors and, thereby, determines whether the mutant virus will have a growth advantage.

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“…Several peculiarities encourage rapid speciation of parasites. Adaptation is mutual, the host also developing adaptive changes (Ahmed et al 1981;Nohinek, Gerhard & Schulze, 1985), and many parasites have developed a very high rate of reproduction that favours variation. Lacking almost every function except programming ability, viruses are amongst the most specialized of parasites.…”

Section: Modes Of Parasitism By Influenza a Virusesmentioning

confidence: 99%

“…Chronic infection describes persistence with regular (even if scanty) production of infectious virions (Medvedeva, Aron & Golubev, 1984a (Ahmed et al 1981). Indeed, the host cell may select variants of influenza A virus and may be exerting as much evolutionary selective pressure as antibody (Schild et al 1983); Nohinek, Gerhard & Schulze, 1985;Patterson & Oxford, 1986).…”

Section: Modes Of Parasitism By Influenza a Virusesmentioning

confidence: 99%

A new concept of the epidemic process of influenza A virus

Hope-Simpson

Golubev

1987

Epidemiol. Infect.

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SUMMARYInfluenza A virus was discovered in 1933, and since then four major variants have caused all the epidemies of human influenza A. Each had an era of solo world prevalence until 1977 as follows: H0N1 (old style) strains until 1946. H1N1 (old style) strains until 1957, H2N2 strains until 1968. then H3N2 strains, which were joined in 1977 by a renewed prevalence of H1N1 (old style) strains.Serological studies show that H2N2 strains probably had had a previous era of world prevalence during the last quarter of the nineteenth century, and had then been replaced by H3N2 strains from about 1900 to 1918. From about 1907 the H3N2 strains had been joined, as now. by H1N1 (old style) strains until both had been replaced in 1918 by a fifth major variant closely related to swine influenza virus A/Hswine1N1 (old style), which had then had an era of solo world prevalence in mankind until about 1929. when it had been replaced by the H0N1 strains that were first isolated in 1933.Eras of prevalence of a major variant have usually been initiated by a severe pandemic followed at intervals of a year or two by successive epidemics in each of which the nature of the virus is usually a little changed (antigenic drift), but not enough to permit frequent recurrent infections during the same era. Changes of major variant (antigenic shift) are large enough to permit reinfection. At both major and minor changes the strains of the previous variant tend to disappear and to be replaced within a single season, worldwide in the case of a major variant, or in the area of prevalence of a previous minor variant.Pandemics, epidemics and antigenic variations all occur seasonally, and influenza and its viruses virtually disappear from the population of any locality between epidemics, an interval of many consecutive months. A global view, however, shows influenza continually present in the world population, progressing each year south and then north, thus crossing the equator twice yearly around the equinoxes, the tropical monsoon periods. Influenza arrives in the temperate latitudes in the colder months, about 6 months separating its arrival in the two hemispheres.None of this behaviour is explained by the current concept that the virus is surviving like measles virus by direct spread from the sick providing endless chains of human influenza A. A number of other aspects of the human host influenza A virus relationship encountered in household outbreaks are among the list of 20 difficulties that are inexplicable by the current concept of direct spread.Alternative concepts have usually been designed to counter particular difficulties and are incompatible with other features of influenzal behaviour in mankind. The new concept detailed in the appendix provides simple explanations for most if not all of the difficulties. It proposes that influenza A virus cannot normally be transmitted during the illness because it too rapidly becomes non-infectious in a mode of persistence or latency in the human host. Many months or a year or two later it is reactivated by a seasonally mediated stimulus which, like all seasonal phenomena, is ultimately dependent on variations in solar radiation caused by the tilt of the plane of earth's rotation in relation to that of its circumsolar orbit. The carriers, who are always widely seeded throughout the world population, become briefly infectious and their non-immune companions, if infected, comprise the whole of the next epidemic. The reactivated virus particles must encounter the immunity they have engendered in the carrier, thus allowing minor mutants an advantage over virions identical with the parent virus, and so favouring antigenic drift and automatic disappearance of predecessor and prompt seasonal replacement. Antigenic shift and recycling of major variants may also be explained by virus latency in the human host.

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Characterization of host cell binding variants of influenza virus by monoclonal antibodies

Cited by 16 publications

References 14 publications

Single amino acid substitutions in the hemagglutinin can alter the host range and receptor binding properties of H1 strains of influenza A virus

Single amino acid substitutions in the hemagglutinin can alter the host range and receptor binding properties of H1 strains of influenza A virus

Host cell-mediated selection of a mutant influenza A virus that has lost a complex oligosaccharide from the tip of the hemagglutinin.

A new concept of the epidemic process of influenza A virus

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