The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take

Figures

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  Figure 1. A simplified rough estimation of Lewis status in different geographical settings (~7.5%, 20%, and 33% in Europe/North America, Central America/Asia, and Sub-Saharan Africa, respectively). The proportion of Lewis-negatives vary widely between populations [12,15,16,23,26,27,28]. Lewis-negative individuals are susceptible to P[6] rotavirus infections, and the relative proportion of P[6] rotavirus infections in a population correspond reasonably well to the proportion of Lewis-negatives in that population. Rotavirus P[6] infections are virtually nonexistent in Europe and North America, but common in Sub-Saharan Africa.

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  Figure 2. A simplified rough estimation of secretor and Lewis status in different geographical settings (~20% non-secretors and ~7.5% Lewis-negative in Europe and North America and 20% non-secretors and ~33% Lewis-negative in Sub-Saharan Africa) [12,15,16,22,23,26,27,28]. Studies have suggested that non-secretors have a lower vaccine response but would also be protected against circulating wildtype strains of the same genotypes which predominantly infect secretors. However, the Lewis negative proportion of non-secretors, could potentially be susceptible to P[6] strains even after vaccination.

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  Figure 3. Human intestinal enteroids (HIEs) infected with a clinical human rotavirus isolate of genotype G3P[8]. Monolayers of differentiated HIEs from jejunum of secretor-positive (HIE 004) and secretor-negative (HIE 002) individuals. Immunofluorescence staining was performed at 24 h post infection. Rotavirus infected secretor-positive (A, 20× B, 10×) and to a lesser extent secretor-negative (C, 10×) monolayers. (D, ~100×) secretor-positive HIE stained for α1,2 fucose and rotavirus. Monolayer of secretor-positive (E, 20×) and secretor-negative (F, 20×) showing overlay of bright-field and α1,2 fucose UEA-I FITC staining. Red = rotavirus, Alexa594; Green = α1,2 fucose, FITC; and Blue = nuclear staining, DAPI.