Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

Abstract

Respiratory syncytial virus (RSV) is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection.

Keywords: epigenetics; metabolites; microbiome; neonatal immunity; respiratory syncytial virus.

Figure 1

Factors that predispose to the development of severe respiratory syncytial virus (RSV) disease. Factors that can impact the immune response during RSV infection are age; lung development is not complete in preterm infants, and the immune system development will continue until the first years of life, and it will be impacted by the microbiome composition of the mother and infant. The infant microbiome would be shape since the prenatal stage by the mother microbiome, and it will continue modifying by postnatal factors such as environmental microbial exposure, mode of delivery, diet, and antibiotic use. The infant microbiome would have long-acting effects on RSV immune responses. All these components independently or together represent the most common elements that are involved in the development of RSV severe disease.

Figure 2

Epigenetic modification alters gene expression through multiple mechansims. (A) DNA methylation occurs at regions that are rich in cytosine and guanine (CpG islands), leading to the repression of gene transcription. (B) MicroRNAs are short, non-coding RNA molecules encoded in the genome that bind to mRNA, leading to mRNA degradation or translational suppression. These matches can either be fully complementary or may contain mismatched bases, allowing one miRNA to target several mRNA molecules. (C) Histone modifications include methylation and acetylation of lysine and arginine residues on histone tails, as well as phosphorylation of serine and threonine residues. Potential modifications of the tail of histone 3 are shown as an example. These modifications result in changes in chromatin structure that can be either repressive or permissive for transcription factor binding.