Human respiratory viral pathogen

The parainfluenza viruses, of which there are four human serotypes, are second only to RSV as a cause of lower respiratory tract illness. There is both a great need for and interest in developing a chemotherapeutic agent for treatment of these two viral, respiratory tract pathogens. The family Picornaviridae contains the genus Rhinovlrus. which is composed of over a hundred distinct serotypes. The rhino-viruses are recognized as the most important causative agents of the... 

The cotton rat (Sigmodon hispidus) is a well-established model for a number of human pathogens, especially viral respiratory pathogens (14,15). The model detailed in this chapter is an adaptation of a model of S. aureus nasal colonization originally described in mice (16) but now adapted to cotton rats. The cotton rat s nasal histology is comparable to that of humans (17) and pretreatment of cotton rats with antibiotics like streptomycin is not required as it is in mice (16) to establish nasal colonization by S. aureus. We have successfully used the cotton rat S. aureus nasal colonization model to demonstrate the efficacy of lysostaphin as a therapy for S. aureus nasal colonization (18) as well as to study the roles of wall teichoic acid (19) and IsdA and IsdH (20) of S. aureus in nasal colonization. 

Assessment of the immimogenic consequences of gene delivery should also be possible in the chosen species this is particularly important for the evaluation of viral vectors. There has been much discussion on the value of using a permissive host to assess potential human risk from these vectors. The natural route of exposure - i.e. respiratory for adenoviruses - traditionally used to assess permissivity, seems unnecessary to assess the safety of gene therapy products, particularly with the core study approach discussed above. Systemically-administered replication-competent adenovirus will infect (i.e. gain entry into the cell) and be pathogenic in numerous tissues (Duncan et al., 1978). Gene expression and viral replication depend on the species, route of exposure, and individual tissue susceptibility (Torres et al., 1996 Bett et al., 1962). Thus i.v. administration of viral vectors to mammalian test species should permit the evaluation of potential toxicity of widely-distributed vectors. 

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