The modelling of infectious diseases in experimental animals provides useful information on the pathogenesis of the disease. A recent article by Wiles and co-authors discuss the limitations of animal models for investigation into bacterial diseases1. However, we believe that the picture is considerably more complicated for viral pathogens. The fact that many bacteria can multiply without a host cell, whereas viruses always require a host cell for replication, underlines one aspect of the complexity of viral pathogenesis. In addition, although we have experimental models for several viral diseases, in many instances, the pathogenic process in experimental animals is different from that observed in the natural host. For example, the foot and mouth disease virus causes vesicular disease in its natural hosts, including cattle, swine and other ruminants. In mice, however, the virus causes encephalitis, therefore it is difficult to judge the consequence of viral infection as compared with the course of disease in the natural host. Although the generation of transgenic mice can provide some advantages, the involvement and co-operation of other receptors or molecules cannot be addressed with these transgenic models.

As is well established, several factors in the environment, other than host itself, influence the outcome of a viral disease. It is therefore difficult to reproduce all of these factors under controlled laboratory conditions. For example, an influenza virus can jump between species such as chicken, swine, cattle, horse and human, and can do so at any time. While jumping between species, the virus undergoes mutations to adapt to a new host. The domestication of the above animal species in south-east Asian countries has been an important reason for the emergence of novel influenza viruses in this region. In addition, the severity of the virus infection in humans can also depend on the propagation of the virus in other hosts before spreading to humans.

Next, the presence of natural immunity against a virus in endemic regions and the genetic background of the host influences the severity of the disease. Owing to continuous exposure, viruses might not cause severe infection in their natural hosts present in disease endemic areas, when compared to natural hosts present in disease-free regions. As natural immunity varies from host to host, it is difficult to mimic a similar situation in experimental models. Also, the diversity of the genetic lineage of experimental animals is limited when compared to that of natural hosts.

Despite several other limitations, the value of experimental models should not be underestimated. They provide valuable information that assists in the design of suitable therapeutic and control measures against infectious diseases. However, it is also important to be aware of the limitations of the experimental models. Finally, although disease outbreaks can have devastating consequences, they provide a wealth of information that cannot be derived from analysis of experimental models. As such, it is crucial that the information and conclusions derived from experimental models and computer-aided programs be complemented with data gathered from natural infectious diseases outbreaks.