RESUMO
Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Susceptibility to disease has been associated with histo-blood group antigens and secretor status; nonsecretors are almost completely resistant to disease. We report a foodborne outbreak of GI.3 NoV gastroenteritis that affected 33/83 (40%) persons. Symptomatic disease was as likely to develop in nonsecretors as in secretors (odds ratio [OR] 1.41, 95% confidence interval [CI] 0.46-4.36 vs. OR 0.71, 95% CI 0.23-2.18, p = 0.57). Moreover, no statistical difference in susceptibility was found between persons of different Lewis or ABO phenotypes. The capsid gene of the outbreak strain shares high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize nonsecretor saliva, as well as synthetic Lewis a. This norovirus outbreak affected persons regardless of secretor status or Lewis or ABO phenotypes.
Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Gastroenterite/epidemiologia , Norovirus , Sistema ABO de Grupos Sanguíneos , Adulto , Sequência de Bases , Infecções por Caliciviridae/sangue , Infecções por Caliciviridae/virologia , Gastroenterite/sangue , Gastroenterite/virologia , Predisposição Genética para Doença , Humanos , Antígenos do Grupo Sanguíneo de Lewis , Dados de Sequência Molecular , Norovirus/genética , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Saliva/virologia , Homologia de Sequência de Aminoácidos , Suécia/epidemiologia , Eliminação de Partículas Virais/genéticaRESUMO
In November 2004, 116 individuals in an elderly nursing home in El Grao de Castellón, Spain were symptomatically infected with genogroup II.4 (GII.4) norovirus. The global attack rate was 54.2%. Genotyping of 34 symptomatic individuals regarding the FUT2 gene revealed that one patient was, surprisingly, a non-secretor, hence indicating secretor-independent infection. Lewis genotyping revealed that Lewis-positive and negative individuals were susceptible to symptomatic norovirus infection indicating that Lewis status did not predict susceptibility. Saliva based ELISA assays were used to determine binding of the outbreak virus to saliva samples. Saliva from a secretor-negative individual bound the authentic outbreak GII.4 Valencia/2004/Es virus, but did not in contrast to secretor-positive saliva bind VLP of other strains including the GII.4 Dijon strain. Amino acid comparison of antigenic A and B sites located on the external loops of the P2 domain revealed distinct differences between the Valencia/2004/Es and Dijon strains. All three aa in each antigenic site as well as 10/11 recently identified evolutionary hot spots, were unique in the Valencia/2004/Es strain compared to the Dijon strain. To the best of our knowledge, this is the first example of symptomatic GII.4 norovirus infection of a Le(a+b-) individual homozygous for the G428A nonsense mutation in FUT2. Taken together, our study provides new insights into the host genetic susceptibility to norovirus infections and evolution of the globally dominating GII.4 viruses.
Assuntos
Infecções por Caliciviridae/genética , Códon sem Sentido/genética , Fucosiltransferases/genética , Sistema ABO de Grupos Sanguíneos/genética , Surtos de Doenças , Ensaio de Imunoadsorção Enzimática , Genótipo , Humanos , Antígenos do Grupo Sanguíneo de Lewis/genética , Norovirus/classificação , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saliva/virologia , Espanha , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.