Studies with a Cold-Recombinant A/Victoria/3/7S (H3N2) Virus. I. Biologic, Genetic, and Biochemical Characterization

Abstract

A cold-recombinant virus CR 22, was derived from an attenuated cold-adapted parent strain. A/Ann Arbor/6/60 (H2N2), and a wild-type parent strain, A/Victoria/3/75 (H3N2). Antigenic analysis showed that CR 22 possesses the hemagglutinin and neruaminidase surface antigens derived from the A/Victoria/3/75 (H3N2) parent. From studies of virus-induced polypeptides using polyacrylamide gel electrophoresis, it was deduced that a polymerase protein, P1, is coded and by an RNA segment derived from the wild-type parent; all other genetic elements are derived from the attenuated parent. The attenuated parent and the recombinant CR 22 both possess temperature-sensitive (ts) lesions, evident by restriction of multiplication in fertile chicken eggs or in Madin-Darby canine kidney cell cultures at greater than or equal to 38 C. Genetic analysis of CR 22 by complementation tests using Hong Kong and Wilson Smith neurotropic ts mutants gave evidence for a ts lesion in the genetic elements coding for complementary RNA.

Animal models for influenza virus pathogenesis, transmission, and immunology

“…In 1940, Monroe D. Eaton published a series of experiments (Eaton, 1940) in which he investigated the murine transmission of mouse-adapted influenza viruses, including PR/8 and the “WS” strain, an influenza virus isolated by Wilson Smith in 1933 -- reportedly from his own throat washings while ill with influenza (Evans, 1966) -- and an ancestor of the still commonly used laboratory strain WSN, its neurotropic variant (“Wilson Smith Neurotropic”) (Reeve et al, 1980). …”

Identification of sequence changes in the cold-adapted, live attenuated influenzavaccine strain, A/Ann Arbor/6/60 (H2N2)

“…After taking into consideration the available data, we suggest that the changes in the ca A/Ann Arbor/6/60 virus that are of particular interest for future study are as follows: (1) the alanine to serine change at amino acid 86 in the M2 protein, (2) the leucine to proline change at amino acid 71 5 in the PA protein, (3) the asparagine to serine change at amino acid 265 in PB2, and (4) any or all of the four changes in the PB1 protein. While it is useful to attempt to identify those changes most likely to be involved in the phenotypic properties of the ca virus, conclusions made at this time must be viewed as preliminary for the following reasons: (1) Some contradictions appear in results from genetic complementation or recombination experiments that used different ts mutant sets (Spring et aL, 1977;Reeve et aL, 1980a;Cox et al, 1981). 2Conclusions about the genetic basis of attenuation made with single segment reassortants may not apply for different wild-type parents.…”

Live influenza A/Victoria/75 (H3N2) virus vaccines: reactogenicity, immunogenicity, and protection against wild-type virus challenge

“…Both CR19 and CR22 have genes which specify hemagglutinin, neuraminidase, and polymerase protein 1 from wild-type ANVictoria/75, and the remaining five genes from the cold-adapted donor (9,18). If one combines results with these very similar A/Victoria/75 CR viruses, the incidence of URI among the 23 volunteers was 17% (four) and that of systemic illness was 9o (two).…”

“…Wild-type influenza A/Victoria/3/75 (H3N2) virus was isolated and grown in specific pathogen-free eggs (14). Production and characterization of the A/ Victoria/75-ts-1[E] recombinant clone 81 (14), the A/ Victoria/75-ts-lA2 recombinant clone 76 (17), and the CR19 (8) and CR22 clone 2 (18) recombinants of A/ Victoria/75 with cold-adapted A/Ann Arbor/6/60 (H2N2) have been described. Each of the recombinant virus vaccine candidates possessed A/Victoria/75 (H3N2) surface antigens and was finally grown in specific pathogen-free eggs.…”