Enteroviruses and Autoimmunity

Based on: https://www.nature.com/articles/s41591-019-0667-0      

Enteroviruses are common throughout the United States. There are a variety of specific viruses that are categorized under this species [1]. Infection typically affects young children and causes fever, runny nose, sneezing, cough, and body aches. Enteroviruses are not usually dangerous and can be fought off by the child’s own immune system [2]. Type 1 diabetes (T1D) and islet autoimmunity are common in the United States as well. T1D is a chronic disease in which the pancreas produces insufficient insulin. Insulin is used by the body to help sugar enter the cells to be used to make energy. The exact cause of T1D is not entirely known. It is an autoimmune disease meaning that the body’s immune system usually attacks itself for unknown reasons [3]. Islet autoimmunity is the early stage of autoimmunity that occurs prior to a diagnosis of T1D [4] . The Vehik et al. paper is studying whether enterovirus can play a role in causing these autoimmunities.

            Vehik et al. wanted to study whether increased amounts of enterovirus infection is correlated with increased T1D or islet autoimmunity. They studied this by collecting fecal matter from 282 children with islet autoimmunity and 112 with T1D, plus age matched controls. The controls were children of roughly the same age who did not have either of these diagnoses. The stool from the controls was used to see what normal levels of virus shed in the fecal matter are. Shedding in terms of viruses is when after a person is infected with a virus the virus is present in bodily secretions (ex. Saliva, blood, stool) where it can be used to infect other people [5]. Then, the virus particles that were excreted in the stool were sequenced to determine the genetic code of the virus. These viruses were then analyzed to determine any correlation between virus particles being shed and disease outcome. Figure 1 shows the different viruses that were identified in the children’s stool. 55.8% of the samples were positive for mammalian viruses with the most prevalent being human adenovirus, parechovirus, Enterovirus A, and Enterovirus B.  In Figure 1C they broke down the percentages of Enteroviruses that were found in the stool and determined that the most prevalent forms of enterovirus were Enterovirus A and coxsackievirus. Coxsackievirus is what causes Hand, Foot, and Mouth disease in children [6]. Figure 1d looks at the likelihood of developing islet autoimmunity based after exposure to certain common human viruses based on the amount of virus positive stool samples. This analysis also showed a positive correlation with Human mastadenovirus F (HAdV-F). WHen HAdV-F was found in the stool, it correlated with lower levels of islet autoimmunity and T1D

Figure 1. Shows association of virus with disease prevalence

           

            This paper looked at global incidences of enterovirus correlation with islet autoimmunity and found results to be somewhat similar worldwide. Next, Vehik et al. did a longitudinal analysis where they looked at the amount of virus that was shed after initial infection to study how long virus could still be identified in stool. They identified virus shedding as prolonged when the virus being shed had 98% or more similarity in the genetic code (RNA). The results show that the same virus was being shed for an average of 6 months in children with islet autoimmunity and 4 months in the matched controls. Therefore, children with prolonged shedding of the same virus had higher odds for developing islet autoimmunity. If the virus with prolonged shedding was coxsackievirus B, then the likelihood of developing islet autoimmunity is even greater. This is seen in Figure 2 which studies the risk of islet autoimmunity based on viral infection frequency. It shows that prolonged shedding increases risk. Meaning, the longer the virus is replicating in the patient and the longer the patient is still producing infectious virus, the higher the likelihood of that patient developing islet autoimmunity is.

 

Figure 2. Shows risk of disease based on viral frequency.

Ultimately, the authors did some genome sequencing to look at mutations in the receptor that the virus binds to on the cell. This showed that certain changes seem to have a higher correlation with islet autoimmunity.This combined with the other results of the paper prove that prolonged shedding of the same virus are associated with higher risk of islet autoimmunity. The type and duration of the viral infection are both key factors in determining a child’s risk. They found a positive correlation with HAdV-F which appears to have a protective factor to prevent islet autoimmunity. HAdV-F binds to the same receptor as coxsackievirus B, indicating a potential for receptor competition which lessons the ability of coxsackievirus B to bind and cause infection. This study is mainly a correlational analysis, and much research is still needed to figure out how these viral infections cause autoimmunity.

Works Cited:

[1] Linden, Lonneke, et al. “Replication and Inhibitors of Enteroviruses and Parechoviruses.” Viruses, vol. 7, no. 8, Aug. 2015, pp. 4529–62. DOI.org (Crossref), doi:10.3390/v7082832.

[2] Non-Polio Enterovirus | About EV-D68 | Enterovirus D68 | CDC. 3 Jan. 2019, https://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html.

[3] “Type 1 Diabetes - Symptoms and Causes.” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011. Accessed 13 Dec. 2019.

[4] “Type 1 Diabetes: Autoimmune Reaction Successfully Halted in Early Stage Islet Autoimmunity.” ScienceDaily, https://www.sciencedaily.com/releases/2018/01/180104120349.htm. Accessed 13 Dec. 2019.

[5] “Viral Shedding.” TheFreeDictionary.Com, https://medical-dictionary.thefreedictionary.com/viral+shedding. Accessed 13 Dec. 2019.

[6]