Science：血凝素是人类流感传播的关键

生物谷

生物谷报道：最近，研究人员发现，流感血凝素看起来在流感病毒在人类中高效地传播上起重要的作用。研究结果发表在最新一期的《science》杂志上。

血凝素是流感病毒表面的一个用来与宿主细胞结合的蛋白质，能高效地传播是造成大流行性流感病毒需要具有的关键性质。了解流感的传播将帮助研究人员阻止流感扩大的挑战，人们目前尤其担心的是禽流感在鸡中的流行以及禽流感扩散到人类的可能性。Terrence M. Tumpey和同事研究了他们2005年重建的1918流感病毒表面的血凝素蛋白质。1918年的流感病毒导致一次流感大流行，估计在1918年到1920年间造成了至少5000万人的死亡，而且该病毒有一些与禽流感病毒类似的基因序列。研究人员改变了1918病毒血凝素的两个氨基酸，将其哺乳动物构型改为禽构型，然后接种给雪貂。雪貂为流感病毒的人类传染性起好的预报作用。接种1918“禽”血凝素病毒导致雪貂患重症，但是健康的雪貂与有病的雪貂近距离的接触没有使它们患病。这些发现提出，一个流感病毒要能高效低传播，其血凝素必须偏爱与人类上呼吸道中的宿主细胞结合，而不是喜欢与鸟的宿主细胞结合。

Fig. 1. Replication in the upper respiratory tract and transmissibility of H1N1 viruses.

Three ferrets were inoculated with 106 PFU of SC18 (A), Tx/91 (B), or Dk/Alb (C) virus and housed in individual cages. Naïve ferrets were placed in cages adjoined to those of the inoculated ferrets, and viral shedding in the upper respiratory tract was assessed on alternating days for inoculated (left) and contact (right) ferrets. Results from individual ferrets are represented. Solid and dotted bars of same shade represent a separate ferret pair housed in adjoined cages. The limit of virus detection was 101.2 EID50/ml.

原文出处：A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission

Terrence M. Tumpey, Taronna R. Maines, Neal Van Hoeven, Laurel Glaser, Alicia Solórzano, Claudia Pappas, Nancy J. Cox, David E. Swayne, Peter Palese, Jacqueline M. Katz, and Adolfo García-Sastre
Science 2 February 2007: 655-659.
One or two changes in the amino acids of a surface protein on the 1918 influenza virus alter the sialic acid linkages sufficiently to greatly reduce transmissibility.
Abstract »| Full Text »| PDF »| Supporting Online Material »|

作者简介：

Adolfo García-Sastre, Ph.D.
Associate Professor, Microbiology

Mailing Address
One Gustave L. Levy Place
Box 1124
New York, NY 10029

Training and Education
PhD University of Salamanca, Spain

Current Research Virology

Our laboratory has developed several techniques which allow the genetic manipulation of negative strand RNA virus genomes. We are currently using this methodology in two major research areas.

1. Generation of negative strand RNA virus vectors: RNA viruses are effective inducers of humoral and cellular immune responses. Therefore, attenuated RNA viruses may be used to express protective antigens of other pathogens for which no safe attenuated strains are available. We are involved in the construction of recombinant influenza and Newcastle disease viruses expressing a variety of B-cell and T-cell epitopes from different pathogens. These recombinant viruses are being used to elicit immune responses against their expressed antigens. Specifically, we are interested in the generation of influenza virus vectors expressing selected antigens from HIV-1, malaria parasites, and tumor cells as a means to induce protective or therapeutic immune responses against these pathogenic agents.

2. Studies on the replication cycle of RNA viruses: The functions of cis- and trans-acting elements in the replication cycle of influenza virus and the interactions of such viral components among themselves and with host components are being investigated. For this purpose, we are introducing specific mutations into the genome of the virus, and the phenotypic characteristics of the generated virus mutants are being analyzed. These studies are also focused on the generation of attenuated influenza viruses with potential use as live vaccines against influenza. In addition, we are investigating the ability of different RNA viruses, including influenza, respiratory syncytial, dengue and SARS viruses, to inhibit the induction of innate antiviral immune responses in their hosts.

Selected Publications
Laboratory Links

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