Abstract
The single gene reassortant virus that derives its PB2 gene from the avian influenza A/Mallard/NY/78 virus and remaining genes from the human influenza A/Los Angeles/2/87 virus exhibits a host range restriction (hr) phenotype characterized by efficient replication in avian tissue and failure to produce plaques in mammalian Madin-Darby canine kidney cells. The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. The nucleotide sequences of the PB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Interestingly, the amino acid at position 627 in every avian influenza A virus PB2 protein analyzed to date is glutamic acid, and in every human influenza A virus PB2 protein, it is lysine. Thus, the amino acid at residue 627 of PB2 is an important determinant of host range of influenza A viruses.
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- Almond J. W. A single gene determines the host range of influenza virus. Nature. 1977 Dec 15;270(5638):617–618. doi: 10.1038/270617a0. [DOI] [PubMed] [Google Scholar]
- Clements M. L., Snyder M. H., Buckler-White A. J., Tierney E. L., London W. T., Murphy B. R. Evaluation of avian-human reassortant influenza A/Washington/897/80 x A/Pintail/119/79 virus in monkeys and adult volunteers. J Clin Microbiol. 1986 Jul;24(1):47–51. doi: 10.1128/jcm.24.1.47-51.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clements M. L., Subbarao E. K., Fries L. F., Karron R. A., London W. T., Murphy B. R. Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers. J Clin Microbiol. 1992 Mar;30(3):655–662. doi: 10.1128/jcm.30.3.655-662.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coelingh K. J., Winter C. C., Murphy B. R., Rice J. M., Kimball P. C., Olmsted R. A., Collins P. L. Conserved epitopes on the hemagglutinin-neuraminidase proteins of human and bovine parainfluenza type 3 viruses: nucleotide sequence analysis of variants selected with monoclonal antibodies. J Virol. 1986 Oct;60(1):90–96. doi: 10.1128/jvi.60.1.90-96.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorman O. T., Donis R. O., Kawaoka Y., Webster R. G. Evolution of influenza A virus PB2 genes: implications for evolution of the ribonucleoprotein complex and origin of human influenza A virus. J Virol. 1990 Oct;64(10):4893–4902. doi: 10.1128/jvi.64.10.4893-4902.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawaoka Y., Krauss S., Webster R. G. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol. 1989 Nov;63(11):4603–4608. doi: 10.1128/jvi.63.11.4603-4608.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luytjes W., Krystal M., Enami M., Parvin J. D., Palese P. Amplification, expression, and packaging of foreign gene by influenza virus. Cell. 1989 Dec 22;59(6):1107–1113. doi: 10.1016/0092-8674(89)90766-6. [DOI] [PubMed] [Google Scholar]
- Murphy B. R., Hinshaw V. S., Sly D. L., London W. T., Hosier N. T., Wood F. T., Webster R. G., Chanock R. M. Virulence of avian influenza A viruses for squirrel monkeys. Infect Immun. 1982 Sep;37(3):1119–1126. doi: 10.1128/iai.37.3.1119-1126.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scholtissek C., Murphy B. R. Host range mutants of an influenza A virus. Arch Virol. 1978;58(4):323–333. doi: 10.1007/BF01317824. [DOI] [PubMed] [Google Scholar]
- Scholtissek C., Rohde W., Von Hoyningen V., Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology. 1978 Jun 1;87(1):13–20. doi: 10.1016/0042-6822(78)90153-8. [DOI] [PubMed] [Google Scholar]
- Snyder M. H., Buckler-White A. J., London W. T., Tierney E. L., Murphy B. R. The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys. J Virol. 1987 Sep;61(9):2857–2863. doi: 10.1128/jvi.61.9.2857-2863.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tian S. F., Buckler-White A. J., London W. T., Reck L. J., Chanock R. M., Murphy B. R. Nucleoprotein and membrane protein genes are associated with restriction of replication of influenza A/Mallard/NY/78 virus and its reassortants in squirrel monkey respiratory tract. J Virol. 1985 Mar;53(3):771–775. doi: 10.1128/jvi.53.3.771-775.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Treanor J., Kawaoka Y., Miller R., Webster R. G., Murphy B. Nucleotide sequence of the avian influenza A/Mallard/NY/6750/78 virus polymerase genes. Virus Res. 1989 Nov;14(3):257–269. doi: 10.1016/0168-1702(89)90006-3. [DOI] [PubMed] [Google Scholar]