- Email: [email protected]
The big picture
COMMENT Horizons 1918 and all that
T-cell choice
T
he 1918 influenza (‘Spanish flu’) was one of the worst outbreaks of infectious disease in living memory, but the cause of this devastating disease has been difficult to track down. Much interest has recently been generated by attempts to sequence viral genes from frozen or preserved tissues of influenza victims who died in the 1918 pandemic. It was hoped that the sequence of the hemagglutinin (HA) gene would be the key to unlock the mysteries of the virus. In particular, the sequence of the HA proteolytic cleavage site has been eagerly anticipated, as highly basic cleavage sites are known to confer virulence properties to avian influenza strains. The recent report from Reid et al.1 details, for the first time, the entire sequence of a 1918 influenza HA. There is no evidence for an avianlike multi-basic cleavage site, so this is unlikely to be the key to influenza pathogenesis in humans. Overall, however, the 1918 gene is the most swine-like of any HA yet sequenced, suggesting that the pandemic strain probably emerged out of the swine population at some point prior to 1918. So what caused such a devastating switch in the virus during the fall of 1918? The hunt for the cause of pandemic influenza will undoubtedly continue until the sequence of the entire virus is known. Even then, we might not know the true cause. In this age of genomics, the answers to our questions might reside outside the gene sequence; the secret could well lie in the complex interplay between multiple virus and host factors and only be discovered by an in-depth study of the molecular biology, pathogenesis and evolution of the virus. 1 Reid, A.H. et al. (1999) Origin and evolution of the 1918 ‘Spanish’ influenza virus hemagglutinin gene, Proc. Natl. Acad. Sci. U. S. A. 96, 1651–1656
Gary Whittaker [email protected]
T
he T-cell immune response to infectious agents has been polarized into two opposing subsets of T cells: Th1 T cells, which produce interferon g and are important against viruses and intracellular bacteria, and Th2 T cells, which produce interleukin 4 and interleukin 10, stimulate the humoral immune response and are important against extracellular pathogens such as helminths. How naive T cells are stimulated to differentiate along either pathway has been the cause of debate since the two subsets were first proposed. Rissoan et al.1 have now provided evidence that the differentiation of naive T cells into two distinct subsets might be due to stimulation by two different types of dendritic cells; myeloid dendritic cells, which stimulate the production of Th1 T cells, and lymphoid dendritic cells, which stimulate the production of Th2 T cells. The article is accompanied by a ‘Perspectives’ review by Kim Bottomley2, which should make easier reading for non-immunologists. 1 Rissoan, M-C. et al. (1999) Reciprocal control of T helper cell and dendritic cell differentiation, Science 283, 1183–1186 2 Bottomley, K. (1999) T cells and dendritic cells get intimate, Science 283, 1124–1125
Barbara Blacklaws [email protected]
The big picture
D
avid Saunder has compiled a Web teaching resource called The Big Picture Book of Viruses (http://www.tulane.edu/ ~dmsander/Big_Virology/ BVHomePage.html). It is a catalogue of virus pictures available on the Web and is intimately linked to the site All the Virology on the WWW (http://www.tulane. edu/~dmsander/garryfavweb. html), which is run from the same lab, and well worth frequent visits. The adjacent image from the ‘book’ shows an animal parapoxvirus (Stewart McNulty at Veteri-
Microbial genomics New DNA sequence viewer and annotation tool Kim Rutherford, working at the Sanger Centre, Hinxton, UK and funded by Beowulf Genomics, has developed Artemis (http://www.sanger.ac. uk/Software/Artemis/index. shtml), a JAVA program that allows the user to visualize sequence features and the results of analyses within the context of a DNA sequence and its sixframe translation. Artemis reads EMBL-format sequences and feature tables and can work on sequences of any size from a few kilobases to entire genomes of >5 Mb. TubercuList Stewart Cole, Ivan Moszer, Maude Klaerr-Blanchar, Louis Jones and coworkers at the Institute Pasteur, Paris, France have constructed the TubercuList Web server (http://www. pasteur.fr/Bio/TubercuList/) around a database dedicated to the analysis of the genomes of the tubercle bacilli. The design of the server is based on the Colibri (http://www.pasteur. fr/Bio/Colibri/) and SubtiList (http://www.pasteur.fr/Bio/ SubtiList/) databases previously created at the Institute Pasteur, which are dedicated to the Escherichia coli and Bacillus subtilis genome sequences, respectively. Mark Pallen [email protected]
nary Sciences, Queen’s University, Belfast, UK). Caroline Ash [email protected]
0966-842X/99/$ - see front matter © 1999 Elsevier Science. All rights reserved. TRENDS
IN
MICROBIOLOGY
189
VOL. 7 NO. 5 MAY 1999
T-cell choice
T
he 1918 influenza (‘Spanish flu’) was one of the worst outbreaks of infectious disease in living memory, but the cause of this devastating disease has been difficult to track down. Much interest has recently been generated by attempts to sequence viral genes from frozen or preserved tissues of influenza victims who died in the 1918 pandemic. It was hoped that the sequence of the hemagglutinin (HA) gene would be the key to unlock the mysteries of the virus. In particular, the sequence of the HA proteolytic cleavage site has been eagerly anticipated, as highly basic cleavage sites are known to confer virulence properties to avian influenza strains. The recent report from Reid et al.1 details, for the first time, the entire sequence of a 1918 influenza HA. There is no evidence for an avianlike multi-basic cleavage site, so this is unlikely to be the key to influenza pathogenesis in humans. Overall, however, the 1918 gene is the most swine-like of any HA yet sequenced, suggesting that the pandemic strain probably emerged out of the swine population at some point prior to 1918. So what caused such a devastating switch in the virus during the fall of 1918? The hunt for the cause of pandemic influenza will undoubtedly continue until the sequence of the entire virus is known. Even then, we might not know the true cause. In this age of genomics, the answers to our questions might reside outside the gene sequence; the secret could well lie in the complex interplay between multiple virus and host factors and only be discovered by an in-depth study of the molecular biology, pathogenesis and evolution of the virus. 1 Reid, A.H. et al. (1999) Origin and evolution of the 1918 ‘Spanish’ influenza virus hemagglutinin gene, Proc. Natl. Acad. Sci. U. S. A. 96, 1651–1656
Gary Whittaker [email protected]
T
he T-cell immune response to infectious agents has been polarized into two opposing subsets of T cells: Th1 T cells, which produce interferon g and are important against viruses and intracellular bacteria, and Th2 T cells, which produce interleukin 4 and interleukin 10, stimulate the humoral immune response and are important against extracellular pathogens such as helminths. How naive T cells are stimulated to differentiate along either pathway has been the cause of debate since the two subsets were first proposed. Rissoan et al.1 have now provided evidence that the differentiation of naive T cells into two distinct subsets might be due to stimulation by two different types of dendritic cells; myeloid dendritic cells, which stimulate the production of Th1 T cells, and lymphoid dendritic cells, which stimulate the production of Th2 T cells. The article is accompanied by a ‘Perspectives’ review by Kim Bottomley2, which should make easier reading for non-immunologists. 1 Rissoan, M-C. et al. (1999) Reciprocal control of T helper cell and dendritic cell differentiation, Science 283, 1183–1186 2 Bottomley, K. (1999) T cells and dendritic cells get intimate, Science 283, 1124–1125
Barbara Blacklaws [email protected]
The big picture
D
avid Saunder has compiled a Web teaching resource called The Big Picture Book of Viruses (http://www.tulane.edu/ ~dmsander/Big_Virology/ BVHomePage.html). It is a catalogue of virus pictures available on the Web and is intimately linked to the site All the Virology on the WWW (http://www.tulane. edu/~dmsander/garryfavweb. html), which is run from the same lab, and well worth frequent visits. The adjacent image from the ‘book’ shows an animal parapoxvirus (Stewart McNulty at Veteri-
Microbial genomics New DNA sequence viewer and annotation tool Kim Rutherford, working at the Sanger Centre, Hinxton, UK and funded by Beowulf Genomics, has developed Artemis (http://www.sanger.ac. uk/Software/Artemis/index. shtml), a JAVA program that allows the user to visualize sequence features and the results of analyses within the context of a DNA sequence and its sixframe translation. Artemis reads EMBL-format sequences and feature tables and can work on sequences of any size from a few kilobases to entire genomes of >5 Mb. TubercuList Stewart Cole, Ivan Moszer, Maude Klaerr-Blanchar, Louis Jones and coworkers at the Institute Pasteur, Paris, France have constructed the TubercuList Web server (http://www. pasteur.fr/Bio/TubercuList/) around a database dedicated to the analysis of the genomes of the tubercle bacilli. The design of the server is based on the Colibri (http://www.pasteur. fr/Bio/Colibri/) and SubtiList (http://www.pasteur.fr/Bio/ SubtiList/) databases previously created at the Institute Pasteur, which are dedicated to the Escherichia coli and Bacillus subtilis genome sequences, respectively. Mark Pallen [email protected]
nary Sciences, Queen’s University, Belfast, UK). Caroline Ash [email protected]
0966-842X/99/$ - see front matter © 1999 Elsevier Science. All rights reserved. TRENDS
IN
MICROBIOLOGY
189
VOL. 7 NO. 5 MAY 1999