A role for arrays in clinical virology: fact or fiction?

Abstract

Microarrays of DNA probes have at least three roles in clinical virology. These are: firstly, in diagnosis, to recognise the causative agent of an illness; secondly, for molecular typing for (i) patient management, (ii) epidemiological reasons (e.g. investigating routes of transmission), (iii) purposes related to vaccine use; and thirdly, in research, to investigate the interactions between the virus and the host cell. Microarrays intended for syndromic diagnostic purposes require genome specific probes to capture the unknown target viral sequences and thereby reveal the presence of that virus in a test sample. Microarrays intended for typing and patient management, e.g. monitoring antiviral drug resistant mutations require a set of probes representing the important sequence variants of one or more viral genes. Microarrays intended for research into virus-host interactions require probes representative of each individual gene or mRNA of either the virus or the host genome. Diagnostic microarrays are dependent for their utility and versatility on generic, multiplex or random polymerase chain reactions that will amplify any of several (unknown) viral target sequences from a patient sample. In this review, the existing and potential applications of microarrays in virology, and the problems that need to be overcome for future success, are discussed.

Fig. 1

An illustration of the processes involved in making and using an array. At the top is depicted the route from the virus of interest to the spotted arrays (herpesvirus and enterovirus particles are shown). At the bottom, DNA or RNA is extracted from samples, amplified and labelled with either Cy3-dCTP (green) or Cy5-dCTP (red). When applied to the array bearing the immobilised probes, the target binds to complementary sequences. An example of an array result is shown on the right: the green spots represent hybridisation of the probe only with target sequences labelled with Cy3-dCTP; the red spots represent hybridisation of the probe only with target sequences labelled with Cy5-dCTP; the yellow spots represent hybridisation with both target sequences.