Why doesn’t everyone get sick with winter vomiting disease?
Collection authors Lennart Svensson, Johan Nordgren & Sumit Sharma ask why everyone doesn’t get sick with winter vomiting disease?
The observation that certain individuals appear to have an inherited factor making them more susceptible or resistant to common infections is not new. Indeed, most of us know individuals who are more frequently ill than others or, the opposite, who are seldom ill. However, not long ago it was assumed that the clinical outcome of an infectious disease was due mainly to virulence factors associated with the microorganism, and little attention was given to host genetics. We are just starting to understand the complex interplay between environmental (microbial and nonmicrobial) and human (genetic and nongenetic) factors that determine immunity to infection or the resulting outcome of an infection. Studies of host genetics effects on susceptibility to infectious diseases have increased rapidly during the last few years. Knowledge of how our genes affect the risk of infection or severe disease provides insight into the pathophysiology of certain virus, immune responses required for protection, and possible targets for vaccine or antiviral treatment.
Inherited factors modulating the outcome of a viral infection or disease could be immunological factors involved in innate or adaptive immunity or could be a viral receptor required by the virus to infect a certain cell. While immunological factors would affect the outcome of an acquired infection, the lack of a receptor would inhibit the virus from infecting the host. A remarkable example of receptor-dependence is the strong Mendelian trait resistance, the most common example for noroviruses is among individuals with a nonsense mutation in chromosome 19.
Mutation in FUT2 on chromosome 19 protects one in five individuals from most common norovirus infections. The earliest volunteer studies in the 1970s used the first isolated norovirus, the Norwalk virus. These early studies hinted that not all individuals were inherently susceptible to norovirus infection. The authors made, at that time, a most provocative hypothesis and suggested host genetic control of susceptibility. In the last decade, challenge and outbreak studies from several countries have confirmed a genetic component to norovirus susceptibility. The presence of histo-blood group antigens (HBGAs) on gut epithelial surfaces are essential for susceptibility to many norovirus genotypes. The synthesis of these HBGAs, specifically of the ABH and Lewis families, requires the use of several fucosyl and glycosyltransferases encoded by the FUT2, FUT3 and ABH genes. Polymorphisms in these genes vary considerably depending on ethnicity, with a homozygous nonsense mutation (individuals called non-secretors) in the FUT2 gene occurring in ~5-50% of different populations worldwide. In the Caucasian population about 20% of individuals are non-secretors and thus strongly protected from the most common strains of norovirus (Fig 1). Overall, observations in various settings and countries have, with a few exceptions, consistently shown strong protection of non-secretors against norovirus G.II.4 infections
Do populations with a higher proportion of secretors have higher rates of norovirus disease? Since distribution of the ABO(H), secretor and Lewis genotypes is strongly dependent on ethnicity, it can be hypothesized that molecular epidemiology differs between regions because of host population genetics. Thus, populations with a higher proportion of secretors would be more susceptible to both secretor-independent and dependent genotypes, including the most common GII.4 virus. In Caucasian, Asian and some African populations, secretors constitute approximately 80% of the population. In contrast, secretor prevalence in Mesoamerican populations can be as high as 95%. While there are some indications that populations with a higher proportion of individuals susceptible to GII.4 have higher rates of disease, more studies are needed to address whether a higher frequency of GII.4 infections, or other secretor dependent genotypes also translates into a higher disease burden.
Are histo blood group antigen polymorphisms at the population level driving the evolution of norovirus? As human HBGAs are associated with increased susceptibility to several pathogens such as HIV, rhinovirus, Haemophilus influenzae, Neisseria meningitidis, and urinary tract infections, it can be speculated that both pathogens and the host are under selection pressure resulting in genetic variation in both the circulating pathogens as well as the human population. This genetic variation may include mutations in the cell and virus receptor mutations. In support of this notion is that genetic and phenotypic diversity of HBGAs have been found to be higher in sub-Saharan African populations compared to many other regions. However, it remains to be shown that secretor-dependent noroviruses are using district cellular receptors in vivo. An interesting study would be to investigate the occurrence of norovirus genotypes in regions with very high proportion of non-secretors.
The Lennart Svensson group at the University of Linköping, Sweden has long investigated the role of host genetic factors involved in viral pathogenesis, and in particular human norovirus infections and disease mechanisms associated with viral gastroenteritis. Our interest in the field arose after scientific reports and our own clinical observations established that certain individuals repeatedly remain resistant to clinical symptoms following norovirus infections.
i haven’t thrown up for 9 years and the last time i really had stomach flu was back in 2010. there been times where my family will be sick but i’m expose to it but those times i did not show any symptoms of the virus. i would wash my hand too to reduce the risk of being sick but would i still get sick even though i been washing my hands.
I only had the flu once in my life and that was the once and only time I have ever received a flu shot.
I have never had the stomach flu.
this in regards to norovirus not the flu
My whole family has the norovirus right now! I am the only one who has yet to get it…I work in a hospital and have had a mandatory flu shot this year already. Fingers are crossed that I don’t get sick! I don’t every remember having the stomach flu though…maybe once when I was a kid/ teen. I’ll update if I do get sick tho! lol