ABSTRACT
Varicella-Zoster virus (VZV) is a human herpes virus that reactivates from a latent state in human trigeminal and dorsal root ganglia to cause herpes zoster (shingles) which is a painful vesicular dermatomal skin eruption. The major complication of herpes zoster is post-herpetic neuralgia (PHN) which is a serious condition occurring especially in individuals over 50 years. PHN is extremely painful, may be permanent, and is frequently very refractory to all treatment. The ability to identify those patients with herpes zoster who are likely to develop PHN would be highly beneficial as it would allow pre-emptive anti-viral therapy. We have assessed the potential of using long oligonucleotide VZV microarrays to determine whether MeWo cells infected with VZV isolates obtained from 13 patients with zoster who had subsequently developed PHN showed significant transcriptomal differences from MeWo cells infected with viruses isolated from ten zoster patients who had not developed PHN. We found that viral gene expression from sample to sample within a group (PHN patients or non-PHN patients) varied as much, or more, than the viral gene expression between those groups. Quantitative real-time polymerase chain reaction studies carried out on 11 open reading frames on four representative viral infected MeWo cell lines (two from each group) confirmed the transcriptomal heterogeneity between the two groups. Growth curve analyses of ten representative infected cell lines (five from each group) showed that PHN and non-PHN-associated viruses replicated equally efficiently. Taken together, these findings suggest that viral microarray-based transcriptomal measurements are unlikely to prove of clinical utility in predicting the incidence of PHN.
Subject(s)
Gene Expression Profiling , Herpes Zoster/virology , Herpesvirus 3, Human/genetics , Herpesvirus 3, Human/pathogenicity , Neuralgia, Postherpetic/virology , Adult , Aged , Aged, 80 and over , Cell Line , Female , Herpesvirus 3, Human/isolation & purification , Humans , Male , Microarray Analysis , Middle Aged , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
We used a rat model of Varicella-Zoster virus (VZV) ganglionic infection, which mirrors some of the features of VZV latency in humans, to determine the temporal pattern of expression of a VZV immediate-early gene (63) and a VZV late gene (40) at 0, 24 and 48 h after death of the animal. The immediate-early VZV gene 63 is known to be abundantly expressed during human ganglionic latency, while the late VZV gene 40 is not expressed during human latency. Using both RNA in situ hybridisation (ISH) and nested RT-PCR, it was found that at all time points in both thoracic and lumbar ganglia, the number of ganglia positive for VZV gene 63 was higher than for gene 40. The expression of gene 40 did not increase with time postmortem (pm) These results provide indirect support for the hypothesis that patterns of expression of VZV genes detected in human tissue at even 48 h pm reflect the pattern of expression during human ganglionic latency.
