Do Vpu and Vpr of human immunodeficiency virus type 1 and NB of influenza B virus have ion channel activities in the viral life cycles?
Do Vpu and Vpr of human immunodeficiency virus type 1 and NB of influenza B virus have ion channel activities in the viral life cycles?
复制标题
1型人类免疫缺陷病毒的Vpu和Vpr以及乙型流感病毒的NB在病毒生命周期中是否具有离子通道活性？
DOI：
10.1006/viro.1997.8451
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Pinto,LH
中科院分区：
文献类型：
--
作者：
Lamb,RA;Pinto,LH
In 1996, three viral proteins, NB of influenza B virus prior to molecular cloning of the cDNA and the expression of the ion channel in heterologous systems. Thus, and Vpu and Vpr of human immunodeficiency virus type 1 (HIV-1), were reported in the literature as having an the characteristics of the channel properties could be anticipated. However, for candidate viral protein ion ion channel activity (Ewart et al., 1996; Piller et al., 1996; Schubert et al., 1996b; Sunstrom et al., 1996). Thus, in- channel activity, prior knowledge of their electrophysiological properties is rarely known. cluding the well-characterized influenza A virus M2 protein, there are now four viral proteins that are reported When a candidate viral ion channel protein is exto act as ion channels. However, demonstrating that a pressed in tissue culture cells or in oocytes of X. laevis viral protein has an ion channel activity that is relevant and a new cell surface conductance is recorded, it is to the life cycle of a virus or in causing viral pathogenesis usually assumed that this current results directly from is not a simple problem. expression of the viral protein. Although this may be a Ion channels are generally accepted to be integral correct conclusion, the caveat must be added that exmembrane proteins that contain an aqueous accessible pression of several small integral membrane proteins of proteinaceous core (the channel pore) that can allow a both viral and cellular origin, at least in the oocyte sysmassive flux of ions (107–108 ions per second) across a tem, is capable of regulating a channel (s) endogenous membrane. In contrast, some water-soluble peptides can to the host cell (Attali et al., 1993; Shimbo et al., 1995; promote the local breakdown of the membrane bilayer Tzounopoulos et al., 1995). Thus, unless a specific creating a lipidic pore with a surface formed completely blocker of the candidate channel is available, it may be or partially by polar lipid headgroups. The biophysical difficult to distinguish whether the current observed is characteristics of these lipidic pores are not as well de- intrinsic to the expressed viral protein. One approach fined as those of ion channels and are usually dependent toward overcoming this dilemma is to make mutations on the lipid composition of the membrane (Chernomordik in the presumptive channel pore region, seek changes et al., 1994). in properties of the channel (eg, altered ionic selectivity, Ion channel activity is detected by measuring changes gating, or inactivity), and correlate these observations in cell surface currents, either of whole cells or of single with the effect of incorporating the same mutations into macromolecular complexes (single channel recordings). the virus genome. One of the simpler methods to analyze ion channel pro- To demonstrate that an ion channel activity is a bona teins is to express the proteins either in tissue culture fide property of the purified channel protein, attempts are cells or in oocytes of Xenopus laevis. This method re- often made to reconstitute the ion channel in planar lipid quires that the candidate protein is expressed at the bilayers. Thus, this technique can be used to confirm surface of cells in order to measure ion channel currents. properties of the ion channel activity measured by other For the ion channels of many specialized cells the nature means. If there is a concordance among the data, then of the surface currents had been measured in organs it can be safely concluded that the ion channel activity is intrinsic to the purified protein. However, in the absence of supporting data interpretation of results ob-
