• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Apr 1993; 67(4): 1761–1764.
PMCID: PMC240216

A single amino acid in the PB2 gene of influenza A virus is a determinant of host range.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (848K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Almond JW. A single gene determines the host range of influenza virus. Nature. 1977 Dec 15;270(5638):617–618. [PubMed]
  • Clements ML, Snyder MH, Buckler-White AJ, Tierney EL, London WT, Murphy BR. 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. [PMC free article] [PubMed]
  • Clements ML, Subbarao EK, Fries LF, Karron RA, London WT, Murphy BR. 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. [PMC free article] [PubMed]
  • Coelingh KJ, Winter CC, Murphy BR, Rice JM, Kimball PC, Olmsted RA, Collins PL. 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. [PMC free article] [PubMed]
  • Gorman OT, Donis RO, Kawaoka Y, Webster RG. 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. [PMC free article] [PubMed]
  • Kawaoka Y, Krauss S, Webster RG. 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. [PMC free article] [PubMed]
  • Luytjes W, Krystal M, Enami M, Parvin JD, Palese P. Amplification, expression, and packaging of foreign gene by influenza virus. Cell. 1989 Dec 22;59(6):1107–1113. [PubMed]
  • Murphy BR, Hinshaw VS, Sly DL, London WT, Hosier NT, Wood FT, Webster RG, Chanock RM. Virulence of avian influenza A viruses for squirrel monkeys. Infect Immun. 1982 Sep;37(3):1119–1126. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Scholtissek C, Murphy BR. Host range mutants of an influenza A virus. Arch Virol. 1978;58(4):323–333. [PubMed]
  • 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. [PubMed]
  • Snyder MH, Buckler-White AJ, London WT, Tierney EL, Murphy BR. 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. [PMC free article] [PubMed]
  • Tian SF, Buckler-White AJ, London WT, Reck LJ, Chanock RM, Murphy BR. 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. [PMC free article] [PubMed]
  • Treanor J, Kawaoka Y, Miller R, Webster RG, Murphy B. Nucleotide sequence of the avian influenza A/Mallard/NY/6750/78 virus polymerase genes. Virus Res. 1989 Nov;14(3):257–269. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...