Host genetic factors affect susceptibility to norovirus infections in Burkina Faso

Abstract

Norovirus (NoV) constitutes the second most common viral pathogen causing pediatric diarrhea after rotavirus. In Africa, diarrhea is a major health problem in children, and yet few studies have been performed regarding NoV. The association of histo-blood group antigens (HBGA) and susceptibility to NoV infection is well established in Caucasian populations with non-secretors being resistant to many common NoV strains. No study regarding HBGA and NoV susceptibility has yet been performed in Africa. We collected 309 stool and 208 saliva samples from diarrheal children in Ouagadougou, Burkina Faso; May 2009 to March 2010. NoV was detected using real-time PCR, and genotyped by sequencing. Saliva samples were ABO, Lewis and secretor phenotyped using in house ELISA assays. NoV was detected in 12% (n = 37) of the samples. The genotype diversity was unusually large; overall the 37 positive samples belonged to 14 genotypes. Only children <2 years of age were NoV positive and the GII.4 NoVs were more frequent in the late dry season (Jan-May). NoV infections were observed less in children with the secretor-negative phenotype or blood group A (OR 0.18; p = 0.012 and OR 0.31; p = 0.054; respectively), with two non-secretors infected with genotypes GII.7 and GII.4 respectively. Lewis-negative (Le(a-b-)) children, representing 32% of the study population, were susceptible to GII, but were not infected with any NoV GI. GII.4 strains preferentially infected children with blood group B whereas secretor-positive children with blood group O were infected with the largest variety of genotypes. This is the first study identifying host genetic factors associated with susceptibility to NoV in an African population, and suggests that while the non-secretor phenotype provides protection; the Lewis b antigen is not necessary for GII infection.

Figure 1. Temporal distribution of norovirus genogroups/genotypes in Ouagadougou, Burkina Faso from end of May 2009 to March 2010; each tick representing 3 weeks.

Rainy season (June-September), cold dry season (December-February).

Figure 2. Phylogenetic analysis of the NS region (nt 1–301, ORF2) of NoV GI strains from Burkina Faso, May 2009–March 2010 with references strains from all known GI genotypes and most similar NoV strains detected in sub-Saharan Africa (panel A).

Phylogenetic analysis of the NS region (nt 1–274) of NoV GII strains from Burkina Faso, May 2009–March 2010 with references strains from all known GII genotypes and most similar identities detected in sub-Saharan Africa (panel B). The Burkina Faso strains are marked with filled circles. Scale bar represents the number of substitutions per site and bootstrap values are shown at branch nodes (values of <50% are not shown).