Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox. Part 3
In Australia widespread preventative measures are taken limit exposure to UVR in schools by having large, shaded playground areas.
In urban Brazil, man-made biomass burning and in rural areas, the forest canopy and high humidity act together to reduce UVR.
In the Congo, the first ever demonstration of transmission of temperate virus, occurred in only one family all living in the same house, the implication being that temperate virus is rapidly inactivated by UVR after leaving the confines of the family home.
Finally, the detection of temperate virus genotypes from cases of chickenpox in Mexico City may be explained because it is one of the most heavily polluted cities in the world which reduces UVR, allowing temperate genotypes to survive.
Proving the hypothesis
The hypothesis is biologically plausible because UVR is virucidal against many viruses, yet the effect of UVR on survival of VZV in vitro has never been tested. However, the effect of UVR on virus transmission in vivo was demonstrated over 60 years ago when artificial UVR was used successfully to reduce virus transmission in US schools to limit spread of chickenpox. Epidemiological evidence to support the hypothesis could be provided by correlating the transmission of different virus genotypes with ambient UV radiation. Genotyping VZV in cases of chickenpox could determine if there are seasonal differences in genotype transmission in temperate areas. The hypothesis would predict that tropical virus genotypes should predominate during summer in temperate countries since they would have the selective advantage of increased resistance to UVR.
If different genotypes of VZV possess different tolerances to UVR this could be demonstrated in vitro by exposing virus to UVR and quantifying the surviving virus by either plaque forming units or quantitative mRNA RT-PCR. Finally, it may also be possible to make hybrid viruses by exchanging those regions of the VZV genome which are significantly different between genotypes and determine for the first time the molecular markers that underlie transmission or reactivation of VZV.
Implications of the hypothesis
The principal difficulty with the hypothesis is explaining how an ancestral tropical virus genotype, inherently more resistant to UVR, migrated with man out of Africa 200,000 years ago only to lose the selective advantage of resistance to UVR, form a temperate virus genotype lineage and as result become less transmissible. The solution to this paradox could be that loss of the selective advantage of resistance to UVR and reduced transmissibility was offset by an increased propensity to reactivate as zoster. This could indicate that the areas of the VZV genome which confer resistance to UVR are the same as are involved in latency and reactivation.
I suspect this to be the case because as the transmission environment is so harsh in the tropics, random mutation and natural selection should have brought about a tropical virus genotype which reactivates much more frequently to counter-act the lower transmissibility of chickenpox. The fact that the data on zoster epidemiology from tropical countries (in the pre-AIDS era) are virtually absent suggests that the tropical genotype reactivates only in severely immune suppressed individuals. 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.