Potentially it may have implications for VZV vaccine since if it was made from a tropical genotype which reactivated much less frequently, it might be possible, in years to come, to significantly reduce the disease burden from zoster
Potentially it may have implications for VZV vaccine since if it was made from a tropical genotype which reactivated much less frequently, it might be possible, in years to come, to significantly reduce the disease burden from zoster. List of abbreviations UVR: Ultra-violet radiation; VZV: Varicella-zoster virus Competing interests The authors declare that they have no competing interests. Authors’ contributions Solely responsible for developing, researching and writing the hypothesis.. during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being RGH-5526 the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity. Testing the Hypothesis The hypothesis is usually testable by exposing different virus genotypes to ultra-violet radiation and quantifying virus survival by plaque forming units or quantitative mRNA RT-PCR. Implications of the hypothesis The ancestral varicella-zoster virus, most probably a tropical genotype, co-migrated with man as he left Africa approximately 200,000 years ago. For this virus to have lost the selective advantage of resistance to ultra-violet radiation, the hypothesis would predict that this temperate, ultra-violet sensitive virus should have acquired another selective advantage as an evolutionary trade-off. One obvious advantage could be an increased reactivation rate as zoster to set up more rounds of chickenpox transmission. If this were so, the mechanism responsible for resistance to ultra-violet radiation might also be involved in reactivation and latency. This could then provide the first insight into a genetic correlate of the survival strategy of this virus. Background Chickenpox epidemiology is unique among human herpes viruses. In the tropics primary contamination is often delayed into later childhood whereas in temperate zones most contamination occurs before leaving school. Indeed, in some tropical countries 30-50% of adults are susceptible, compared with only 5-10% from temperate areas [1]. Conventionally, transmission has been considered to occur by shedding of virus from the upper respiratory tract 1-2 days before the rash [2,3]. The papers which claim to show such virus transmission however, also conclude that this titres of virus in vesicular fluid are considerably greater than those present in the pharynx and that vesicular virus makes the greatest contribution to spread [4-6]. Indeed, the few papers cited as providing epidemiological evidence for airborne spread are either mis-quoted [7], based on case reports [8,9] or do not reflect the normal transmission environment[10]. In this regard chickenpox appears similar to smallpox, which also had a distinct GREM1 winter-spring seasonal peak in incidence and was spread RGH-5526 partly RGH-5526 by the vesicular eruption [11]. Why such a common, global contamination should be less common in children from the tropics when infections are generally more common remains unknown. Although previously suggested factors such as heat, humidity, viral interference, population density or contamination with cross-protecting viruses, have been suggested as possible causes of the epidemiological differences, a unified, coherent explanation has eluded discovery [1,12]. The climatic factor which I propose to show is responsible for the geographical differences in transmission is usually ultra-violet radiation (UVR). Furthermore, as varicella-zoster virus (VZV) exists only in man, I propose that UVR has been involved in the co-evolution of virus as man migrated out of Africa. The evolution of varying degrees of resistance to UVR among the different genotypes [13] may also have implications for virus reactivation as zoster. Presentation of the hypothesis A search for sero-epidemiological studies of varicella-zoster virus (VZV) using the terms “varicella”, “chickenpox” and “seroepidemiology” produced a total of 25 papers. From these publications other relevant references were also located giving a total of 42 articles, reviewed in [14]. Whilst the studies were of different formats, linear regression curves of age-stratified antibody prevalence plotted against latitude showed a reasonably good fit (r2 0.5) was demonstrated across all age groups of children 5 years (Determine ?(Figure1).1). The same antibody prevalence data when plotted against temperature, rainfall, population density and sunshine, using data drawn from the World Meteorological Organisation (http://www.wmo.int) and the United Nations (http://www.fao.org/WAICENT/FAOINFO/SUSTDEV/EIdirect/CLIMATE/EIsp0002.htm), showed no consistent correlation (Figures ?(Figures2,2, ?,3,3, ?,44 and ?and55). Open in a separate window Physique 1 Latitude and prevalence of.