Influenza virus infection of newborn rats: Virulence of recombinant strains prepared from a cold-adapted, attenuated parent

Abstract

Infant rats were infected with one of a series of influenza A viruses. The growth of viruses in the turbinates or lungs, and the ability of virus infection to potentiate a subsequent bacterial infection by Haemophilus influenzae (HIb), were measured. The three virus strains known to be virulent for man grew to relatively high titres of 10(5.2)--10(6.8) EBID50/ml in the turbinates of infant rats at 48 hours post-infection, and virus infection enhanced subsequent systemic infection following intranasal inoculation of rats with HIb. In contrast, influenza virus A/Ann Arobr/6/60--P17 and the three recombinant viruses prepared from this strain, all of which are attenuated for man, replicated to significantly lower titres of 10(2.6)--10(4.1) EBID50/ml in infant rats turbinates, and failed to promote systemic infection by HIb to the samest that the behaviour of influenza viruses in infant rats may be an indication for virus virulence for man, and thus provide a test which could facilitate the development of live, attenuated virus vaccines.

Influenza virus infection of newborn rats: virulence of recombinant strains prepared from influenza virus strain A/Okuda/57

“…Thus, relatively high titres of virus were found in the lungs of infant rats inoculated with strains A/Finland/74 and WRL105, which were the two viruses that gave the highest titres in turbinate extracts; virus was I). Two control viruses were studied in parallel with the above experiments; these were virulent strains A/Victoria/75 and attenuated 4A2; the results obtained with these were similar to those found in previous studies (Mahmud et al, 1979b). Thus, strain A/Victoria/3/75 grew to > lo5 EBIDSO/ml at 24 and 48 h p.i.…”

Relative immunogenicity of the cold-adapted influenza virus A/Ann Arbor/6/60 (A/AA/6/60-ca), recombinants of A/AA/6/60-ca, and parental strains with similar surface antigens

“…This reduction is probably related to the decreased capacity of ca viruses to multiply in the respiratory tract (Fig. 2), which has also been observed with inbred CBA/H mice (12), ferrets (7), hanWters (17), and newborn rats (8).…”

Infant rat model of attenuation for recombinant influenza viruses prepared from cold-adapted attenuated A/Ann Arbor/6/60

“…Thus, a laboratory test which could determine virulence in humans would be a great advantage in vaccine development. Virus infection in infant rats has been extensively investigated in this laboratory as a model for human virulence (10,13,17,28). Some 40 virus strains have been tested in this model, and for 38 strains virulence in rats correlated with the known virulence in humans (10).…”

“…Some 40 virus strains have been tested in this model, and for 38 strains virulence in rats correlated with the known virulence in humans (10). Studies with coldadapted recombinant strains (14) showed complete correlation between attenuation in humans and in rats; however, relatively few of these strains have been tested to date (13). In the present report, 21 recombinant strains prepared from cold-adapted A/Ann Arbor/6/60 and 6 dis-on October 6, 2020 by guest http://iai.asm.org/ Downloaded from tinct wild-type strains of influenza A virus were studied in infant rats.…”