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Human Ads (adenoviruses) have been extensively utilized for the development of vectors for gene transfer, as they infect many cell types and do not integrate their genome into host-cell chromosomes. In addition, they have been widely studied as cytolytic viruses, termed oncolytic adenoviruses in cancer therapy. Ads are non-enveloped viruses with a linear double-stranded DNA genome of 30-38 kb which encodes 30-40 genes. At least 52 human Ad serotypes have been identified and classified into seven species, A-G. The Ad capsid has icosahedral symmetry and is composed of 252 capsomers, of which 240 are located on the facets of the capsid and consist of a trimeric hexon protein and the remaining 12 capsomers, the pentons, are at the vertices and comprise the penton base and projecting fibre protein. The entry of Ads into human cells is a two-step process. In the first step, the fibre protein mediates a primary interaction with the cell, effectively tethering the virus particle to the cell surface via a cellular attachment protein. The penton base then interacts with cell-surface integrins, leading to virus internalization. This interaction of the fibre protein with a number of cell-surface molecules appears to be important in determining the tropism of adenoviruses. Ads from all species, except species B and certain serotypes of species D, utilize CAR (coxsackie and adenovirus receptor) as their primary cellular-attachment protein, whereas most species B Ads use CD46, a complement regulatory protein. Such species-specific differences, as well as adaptations or modifications of Ads required for applications in gene therapy, form the major focus of the present review.

A 38-residue fragment is isolated from carboxymethylated plasminogen. have the same sequence as the amino-terminal end of the light chain of plasmin. The sequence 1-28 is therefore the sequence of the carboxyl-terminal end of the heavy chain and contains the specific sequence at which urokinase (EC 3.4.99.26) and other plasminogen-activating serine proteases split. Two of the five carboxymethyl-cysteine residues in the isolated fragment are situated close to the cleavage site and the fragment is not itself a substrate for plasminogen-activators. Residues 1-11 show extensive sequence homology with residues 137-147 and 242-252 in rot rombin, which are located in corresponding regions of the two internally homologous 83-residue structures in the non-thrombin part of the molecule, indicating that such structures may be a common feature of the non-protease part of the larger serine protease zymogens. The determination of the complete primary structure of prothrombin (1, 2) has led to the realization that the activation catalyzed by Factor Xa (prothrombinase, EC 3.4.21.6) involves the cleavage of only two peptide bonds, namely Arg274-Thr and Arg23-Ile. Prothrombin also contains a single thrombin-sensitive bond (Argl'6-Ser). The two FactorXa-sensitive bonds are preceded by the identical tetrapeptide sequences -Ile271-Glu-Gly-Arg-and Ile320-Glu-Gly-Arg, whereas the corresponding residues at the thrombin-sensitive site are different, namely -Vall'3-I1e-Pro-Arg. These findings indicated that a specific oligopeptide sequence immediately preceding the bond to be cleaved is required to define a particular protein as being a substrate for one of those highly specific trypsin-like serine proteases, such as Factors Xa, IXa, XIa, XIIa of the blood coagulation system, urokinase (EC 3.4.99.26) and others of the fibrinolytic system, kallikrein, and the proteolytic components of the complement system, which are involved in the activation and control of many extracellularly regulated processes. To test this possibility with respect to Factor Xa specificity we recently synthesized the compound Tos-LIle-LGlu-Gly-LArgp-nitroanilide and found it to be a good substrate for Factor Xa, but not for thrombin (EC 3.4.21.5), plasmin (EC 3.4.21.7), urokinase or streptokinase-plasminogen complex (T. E. Petersen, L. Sottrup-Jensen, and S. Magnusson, in preparation). The rate of Factor-Xa-catalyzed cleavage of this synthetic compound could not by itself explain the rapid rate of activation of prothrombin. One possible explanation for this is that the two -Ile-Glu-Gly-Arg-sequences may be

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