Resident viruses and their interactions with the immune system

Abstract

The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human 'virobiota' and its associated genes (the 'virome'), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota-immune system interactions for human health.

Figure 1. Anatomical locations of resident viruses in humans.

The human body is populated by resident viruses that include both prokaryotic and eukaryotic viruses. These viruses are associated with various tissues, including the oral cavity, nasopharynx, gastrointestinal and respiratory tracts, and the skin surface. Studies that identified viruses in various host tissues are referenced.

Figure 2. Pathogenic viral infection results in the expansion of the enteric virobiota.

Pathogenic immunodeficiency viruses including SIV and possibly HIV can influence the expansion of resident viral populations in the intestinal tract. Expansion is likely promoted by immune suppression imposed upon the host by the pathogenic virus. Immune suppression results in a global host immune deficiency, allowing select enteric viruses to overpopulate the intestinal tract. Expansion of resident viruses is associated with damage to intestinal epithelial cells. This subsequently allows translocation of enteric viruses, commensal bacteria and bacterial antigens across the epithelial surface, resulting in inflammation and systemic infection. These findings highlight the role of the immune system in controlling intestinal virus populations.

Figure 3. Model for bacteriophage recognition by antiviral innate immune sensors.

DNA and RNA phages could be sensed by components of the mammalian innate immune system if cells directly phagocytize phage particles or if phages are delivered to the intracellular environment by phage-producing bacteria. After degradation of the phage particle, phagocytized phage nucleic acids could be sensed by endosomal Toll-like receptors such as TLR7 or TLR9. If intracellular phages are uncoated in the cytoplasm, the released nucleic acids could be sensed by the sensors cGAMP synthase (DNA) or RIG-I (RNA), which signal through stimulator of interferon genes (STING) and mitochondrial antiviral-signaling protein (MAVS), respectively. These viral nucleic acid sensors activate the transcription factors NF-κB, IRF3 and IRF7 to promote the transcription of antiviral effectors such as IFN-β and proinflammatory cytokines.