Biochemical evidence that "new" influenza virus strains in nature may arise by recombination (reassortment).

Desselberger, Ulrich; Nakajima, Kazuki; Alfino, Paul; Pedersen, Finn Skou; Haseltine, William A.; Hannoun, C.; Palese, Peter

doi:10.1073/pnas.75.7.3341

Cited by 78 publications

(51 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, a few spots were present in more than one segment. Similar observations have been made previously (9). However, sufficient characteristic oligonucleotides were present in viral RNA segments and DI RNAs for specific identification.…”

supporting

confidence: 89%

Sequence relationships among defective interfering influenza viral RNAs.

Davis¹,

Nayak²

1979

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

View full text Add to dashboard Cite

Each clone of ts-52 and ts+ WSN influenza virus, when serially passaged at high multiplicity, gives rise to defective interfering (DI) virus with a unique set of new RNA species. The new RNAs (DI RNA) from several DI viruses were examined by the technique of RNase T1 oligonucleotide two-dimensional electrophoresis. It was found that each DI RNA arises from a specific segment of standard viral RNA. All DI RNA studied arose from the viral polymerase genes (P1, P2, and P3). DI RNAs originating from the same polymerase gene were interrelated. Certain of these DI RNAs appeared to contain completely overlapping nucleotide sequences. Others contained both overlapping and nonoverlapping nucleotide sequences. The latter DI RNAs may be formed from the progenitor viral RNA segment by a mechanism other than a common initiation (or termination) point and a simple deletion from one end.

show abstract

supporting

confidence: 89%

Sequence relationships among defective interfering influenza viral RNAs.

Davis¹,

Nayak²

1979

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

View full text Add to dashboard Cite

show abstract

“…The data represent mean values; the error bars denote standard deviations. gene segments (32,33). This host adaptability can be a result of a series of specific viral mutations found in the various influenza gene segments.…”

Section: Discussionmentioning

confidence: 99%

“…Temperature-dependent ApG primer-initiated RNA synthesis profiles of avian Glu-627 and human E627K PB2 influenza A virus RNA polymerase complex proteins purified from baculovirus expression system. A, ApG primer was extended by Glu-627 and E627K Pol proteins purified from insect cells at five different physiologically relevant temperatures (30,32,34,37, and 42°C) as described under "Experimental Procedures." The 30-nt reaction products are radioactively labeled by the incorporation of [␣-…”

Section: Effect Of the Human E627k Pb2 Mutation On Temperaturedependementioning

confidence: 99%

Biochemical Impact of the Host Adaptation-associated PB2 E627K Mutation on the Temperature-dependent RNA Synthesis Kinetics of Influenza A Virus Polymerase Complex

Aggarwal

Dewhurst

Takimoto

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Most avian influenza A viruses, which preferentially replicate at the high temperatures found in the digestive tract of birds, have a glutamic acid at residue 627 of the viral RNA polymerase PB2 subunit (Glu-627), whereas the human viruses, which optimally replicate at the low temperatures observed in the human respiratory tract, have a lysine (Lys-627). The mechanism of action for this mutation is still not understood, although interaction with host factors has been proposed to play a major role. In this study, we explored an alternative, yet related, hypothesis that this PB2 mutation may alter the temperature-dependent enzymatic polymerase activity of the viral polymerase. First, the avian polymerase protein, which was purified from baculovirus expression system, indeed remained significantly active at higher temperatures (i.e. 37 and 42°C), whereas the human E627K mutant drastically lost activity at these high temperatures. Second, our steady-state kinetics data revealed that the human E627K mutant polymerase is catalytically more active than the avian Glu-627 polymerase at 34°C. Importantly, the E627K mutation elevates apparent K cat at low temperatures with little effect on K m , suggesting that the E627K mutation alters the biochemical steps involved in enzyme catalysis rather than the interaction with the incoming NTP. Third, this temperature-dependent kinetic impact of the human E627K mutation was also observed with different RNA templates, with different primers and also in the presence of nucleoprotein. In conclusion, our study suggests that the amino acid sequence variations at residue 627 of PB2 subunit can directly alter the enzyme kinetics of influenza polymerase.

show abstract

“…Influenza A viruses are sometimes transmitted from one sort of host to another, and hybridism by genetic reassortment between variants occurs readily in the natural setting (Webster, Hinshaw & Bean, 1977;Desselberger et al 1978;Yamane et al 1978;Bean, Cox & Kendal, 1980). Nevertheless, one should not underestimate the degree to which some variants of influenza A virus have become specifically adapted to particular host species (e.g.…”

Section: Modes Of Parasitism By Influenza a Virusesmentioning

confidence: 99%

“…Reassortment requires that a single host individual shall be infected simultaneously with virions of two or more different major serotypes. Reassortment of influenza A virus genes occurs readily in nature, especially in birds, in which several strains of influenza A virus commonly co-infect single birds (Webster & Campbell, 1974); Scholtissek, Koennicke & Rott, 1978;Desselberger et al 1978;Gardner & Shortridge, 1979;Hinshaw et al 1980).…”

Section: Protracted Infection and DI Particlesmentioning

confidence: 99%

A new concept of the epidemic process of influenza A virus

Hope-Simpson

Golubev

1987

Epidemiol. Infect.

View full text Add to dashboard Cite

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.

show abstract

Biochemical evidence that "new" influenza virus strains in nature may arise by recombination (reassortment).

Cited by 78 publications

References 15 publications

Sequence relationships among defective interfering influenza viral RNAs.

Sequence relationships among defective interfering influenza viral RNAs.

Biochemical Impact of the Host Adaptation-associated PB2 E627K Mutation on the Temperature-dependent RNA Synthesis Kinetics of Influenza A Virus Polymerase Complex

A new concept of the epidemic process of influenza A virus

Contact Info

Product

Resources

About