Genetic Composition and Virulence of Influenza Virus: Differences in Facets of Virulence in Ferrets between Two Pairs of Recombinants with RNA Segments of the Same Parental Origin

Campbell, D. J.; Sweet, C.; Hay, Alan J.; Douglas, A. R.; Skehel, J.J.; Mason, Thomas J.; Smith, H.

doi:10.1099/0022-1317-58-2-387

Cited by 11 publications

(2 citation statements)

References 24 publications

(17 reference statements)

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“…The virulence of reassortants containing FM-MA segment 4 in combination with one of each of segments 5, 6, 7, or 8 is shown in Table 6. Several of these reassortants were less virulent than reassortants containing segment 4 alone, indicating that reversion had occurred (either by back mutation or by suppression) during their preparation. Q7 and Q13 were revertants, thus, no effect could be shown for segment 5.…”

Section: Resultsmentioning

confidence: 99%

Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4, 5, 7, and 8

Brown

1990

J Virol

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To cause disease, influenza virus must possess several genetically determined abilities that mediate stages in pathogenesis. The virulent mouse-adapted variant A/FM/1/47-MA (FM-MA), derived from the avirulent A/FM/1/47 (FM) strain, had acquired mutations in genes that control virulence. The purpose of this study was to identify those genes that had mutated to result in increased virulence and to obtain viruses that differed in virulence because of differences in individual genome segments. The genes that had mutated to increase virulence were initially identified by genetic analysis of reassortants obtained by crossing FM-MA with the avirulent strain A/HK/1/68 (HK). FM-MA genome segments 4, 5, 7, and 8 were significantly associated with virulence, as determined by using the Wilcoxon ranked sum analysis. The role of FM-MA segments 4, 7, and 8 was confirmed by reintroduction of these genes into the parental strain, which also provided virus strains that differed in virulence because of mutations in individual genome segments. Segments 4, 7, and 8 were responsible for a 103 6-fold increase in virulence that was proportioned 102-2_, 100-7-. and 10°8-fold, respectively. The role of segment 5 could not be confirmed on transfer back into the parental strain because of reversion during preparation of such reassortants. The incidence of reversion was shown to be significantly associated with culturing of FM-MA in chicken embryo cells but was not associated with growth in MDCK cells. The genetic analysis of FM-MA suggests that adaptation to increased virulence is an incremental process that involves the acquisition of mutations in multiple genes, each of which plays an individual role in pathogenesis. The structural and functional properties of segments 4, 7, and 8 that control the virulence of FM-MA can now be determined by using viruses that differ in virulence because of mutations in these individual genome segments.

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Section: Resultsmentioning

confidence: 99%

Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4, 5, 7, and 8

Brown

1990

J Virol

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“…We also studied the in-vivo anti-in¯uenza-virus activity in ferrets, a good model for in¯uenza virus infection in man (Capbell et al 1982;Smith & Sweet 1988). Ferrets are highly susceptible to infection with unadapted in¯uenza virus strains; infection produces a clinical response similar to that observed in in¯uenza-virus-infected humans, with symptoms including a febrile reaction, nasal obstruction and an increase in nasal-wash protein.…”

Section: In-vivo Anti-in¯uenza-virus Activity Using Infected Ferretsðmentioning

confidence: 99%

Development of Anti-influenza Drugs: II. Improvement of Oral and Intranasal Absorption and the Anti-influenza Activity of Stachyflin Derivatives

Yoshimoto

Yagi

Ono

et al. 2000

Journal of Pharmacy and Pharmacology

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The in-vivo anti-influenza-virus activity of Stachyflin derivatives (III and its phosphate ester, III-Phos), a new class of haemagglutinin fusion inhibitor, and the improvement of their absorption after oral or intranasal administration were studied in mice, rats, and ferrets. The absorption of III in PEG 4000 and III-Phos aqueous solution increased about three and four fold in AUC after oral administration to uninfected mice compared with that of 0.5% HPMC (hydroxypropyl-methylcellulose) suspension. Using a mouse influenza virus infection model, significant anti-influenza-virus activity was observed in infected mice treated orally with these compounds dissolved in PEG 4000 or distilled water, respectively, but not in mice treated with 0.5% HPMC. The in-vivo anti-influenza-virus activity in ferrets, a good model for influenza virus infection in man, was also studied. Although the concentration of III in plasma was above the IC50 against the influenza virus strain used for 6h after the oral administration of III in PEG 400 to uninfected ferrets, no in-vivo anti-influenza-virus activity was observed at the same dosage given 4 times daily for 3 days. The intranasal administration of III-Phos, which was expected to have a more notable in-vivo anti-influenza-virus activity, was examined. III-Phos, whose intranasal absorption had been improved by the modification of III with phosphate ester in rats, inhibited viral replication in the nasal cavity and suppressed influenza-virus-induced fever when administered intranasally to infected ferrets. This study demonstrates that intranasally administered compounds with anti-influenza-virus activity must permeate the nasal membranes to produce their anti-influenza-virus effect.

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Attenuated influenza virus vaccines

Potter

1994

Reviews in Medical Virology

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Genetic Composition and Virulence of Influenza Virus: Differences in Facets of Virulence in Ferrets between Two Pairs of Recombinants with RNA Segments of the Same Parental Origin

Cited by 11 publications

References 24 publications

Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4, 5, 7, and 8

Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4, 5, 7, and 8

Development of Anti-influenza Drugs: II. Improvement of Oral and Intranasal Absorption and the Anti-influenza Activity of Stachyflin Derivatives

Attenuated influenza virus vaccines

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