Hypothesis and rebuttal: UV is affecting chickenpox and shingles – 2011

Abstracts of article and rebuttal both on this page
Both PDFs are attached
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Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa.

Virol J. 2011 Apr 23;8:189.
Rice PS.
Department of Medical Microbiology, St George's Hospital, Blackshaw Road, London, SW17 0QT, UK. price@sgul.ac.uk.

BACKGROUND: Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection.

PRESENTATION OF THE HYPOTHESIS: Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs 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 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 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 the 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.

PMID: 21513563
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Is ultra-violet radiation the main force shaping molecular evolution of varicella-zoster virus?

Virol J. 2011 Jul 27;8:370.
Vaughan G, Rodríguez-Castillo A, Cruz-Rivera MY, Ruiz-Tovar K, Ramírez-González JE, Rivera-Osorio P, Fonseca-Coronado S, Carpio-Pedroza JC, Cazares F, Vazquez-Pichardo M, Anaya L, Escobar-Gutiérrez A.
Departamento de Investigaciones Inmunológicas, Instituto de Diagnóstico y Referencia Epidemiológicos, Secretaría de Salud, México City, México.

BACKGROUND: Varicella (chickenpox) exhibits a characteristic epidemiological pattern which is associated with climate. In general, primary infections in tropical regions are comparatively less frequent among children than in temperate regions. This peculiarity regarding varicella-zoster virus (VZV) infection among certain age groups in tropical regions results in increased susceptibility during adulthood in these regions. Moreover, this disease shows a cyclic behavior in which the number of cases increases significantly during winter and spring. This observation further supports the participation of environmental factors in global epidemiology of chickenpox. However, the underlying mechanisms responsible for this distinctive disease behavior are not understood completely. In a recent publication, Philip S. Rice has put forward an interesting hypothesis suggesting that ultra-violet (UV) radiation is the major environmental factor driving the molecular evolution of VZV.

DISCUSSION: While we welcomed the attempt to explain the mechanisms controlling VZV transmission and distribution, we argue that Rice's hypothesis takes lightly the circulation of the so called "temperate VZV genotypes" in tropical regions and, to certain degree, overlooks the predominance of such lineages in certain non-temperate areas. Here, we further discuss and present new information about the overwhelming dominance of temperate VZV genotypes in Mexico regardless of geographical location and climate.

SUMMARY: UV radiation does not satisfactorily explain the distribution of VZV genotypes in different tropical and temperate regions of Mexico. Additionally, the cyclic behavior of varicella does not shown significant differences between regions with different climates in the country. More studies should be conducted to identify the factors directly involved in viral spreading. A better understanding of the modes of transmissions exploited by VZV and their effect on viral fitness is likely to facilitate the implementation of preventive measures for disease control.

PMID: 21794170


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