Temperature-Sensitive Mutants of Influenza A Virus: Transfer of the Two Temperature-Sensitive Lesions in the Udorn/72-ts-1A2 Virus to the A/Hong Kong/123/77 (H1N1) Wild-Type Virus
AUTOR(ES)
Murphy, Brian R.
RESUMO
The influenza A/Udorn/72-ts-1A2 virus possesses temperature-sensitive mutations in the genes coding for the P1 and P3 polymerase proteins. It is being evaluated as a donor of its attenuating temperature-sensitive genes to produce recombinant live vaccine strains of epidemic variants of influenza A virus. Transfer of the P1 and P3 genes to two viruses within the H3N2 subtype of influenza A virus (i.e., the A/Victoria/3/75 and A/Alaska/6/77 viruses) conferred on each variant the following properties: (i) 37°C shutoff temperature for plaque formation, (ii) almost complete restriction of viral replication in the lungs, (iii) a 100-fold restriction of viral replication in the nasal turbinates, and (iv) genetic stability after replication in hamsters. This study was undertaken to determine whether the transfer of the two ts-1A2 temperature-sensitive genes into a virus belonging to the H1N1 subtype (i.e., the A/Hong Kong/123/77 virus) would result in a restriction of replication in vitro and in vivo comparable to that observed with the previously studied H3N2 recombinant viruses in hamsters. This was found to be the case. In addition, infection of hamsters with the A/Hong Kong/77-ts-1A2 virus induced significant resistance to infection with wild-type A/Hong Kong/77 virus. Thus, the two ts-1A2 temperature-sensitive genes attenuated influenza A viruses belonging to two distinct subtypes to a specific and predictable level. An unexpected genetic interaction was observed between several A/Hong Kong/77-ts-1A2 segregants bearing the group 5 (P1) temperature-sensitive lesion. One interpretation of these results is that intracistronic complementation occurred between these segregants.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=551020Documentos Relacionados
- Evaluation of Influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and Cold-Adapted Recombinant Viruses in Seronegative Adult Volunteers
- Molecular cloning of two paralytogenic, temperature-sensitive mutants, ts1 and ts7, and the parental wild-type Moloney murine leukemia virus.
- Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK.
- Cellular localization of the transforming protein of wild-type and temperature-sensitive Fujinami sarcoma virus.
- Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression.