The mechanisms of nerve injury caused by viral infection in the occurrence of gastrointestinal motility disorder-related diseases

Abstract

Gastrointestinal motility refers to the peristalsis and contractility of gastrointestinal muscles, including the force and frequency of gastrointestinal muscle contraction. Gastrointestinal motility maintains the normal digestive function of the human body and is a critical component of the physiological function of the digestive tract. At present, gastrointestinal motility disorder-related diseases are gradually affecting human production and life. In recent years, it has been consistently reported that the enteric nervous system has a coordinating and controlling role in gastrointestinal motility. Motility disorders are closely related to functional or anatomical changes in the gastrointestinal nervous system. At the same time, some viral infections, such as herpes simplex virus and varicella-zoster virus infections, can cause damage to the gastrointestinal nervous system. Therefore, this paper describes the mechanisms of viral infection in the gastrointestinal nervous system and the associated clinical manifestations. Studies have indicated that the means by which viruses can cause the infection of the enteric nervous system are various, including retrograde transport, hematogenous transmission and centrifugal transmission from the central nervous system. When viruses infect the enteric nervous system, they can cause clinical symptoms, such as abdominal pain, abdominal distension, early satiation, belching, diarrhea, and constipation, by recruiting macrophages, lymphocytes and neutrophils and regulating intestinal microbes. The findings of several case‒control studies suggest that viruses are the cause of some gastrointestinal motility disorders. It is concluded that one of the causes of gastrointestinal motility disorders is viral infection of the enteric nervous system. In such disorders, the relationships between viruses and nerves remain to be studied more deeply. Further studies are necessary to evaluate whether prophylactic antiviral therapy is feasible in gastrointestinal motility disorders.

Keywords: Enteric nervous system; Gastrointestinal motility; Viral infection.

Fig. 1

Literature search flow chart

Fig. 2

Mechanisms by which various viruses infect and spread to the ENS

Fig. 3

Some specific mechanisms of viral infection. A. VZV infects unmyelinated sensory nerve endings and is transported in a retrograde manner. B. RTX prevents HSV-1 entry into the ENS by disrupting peripheral TRPV1 nociceptors. C. HIV Tat promotes the LPS-TLR4-MyD88-NF-κB pathway through TLR4, thereby promoting the release of inflammatory factors

Fig. 4

Gastrointestinal responses following viral infection of the ENS. After entering the GI tract, different viruses pass through the intestinal mucosa through their own means. HSV-1 is directly taken up and transported by intestinal epithelial cells and then enters the ENS axon terminals. Alternatively, it crosses intestinal epithelial cells by disrupting tight junctions between cells. SARS-CoV-2 is transported through the ACE2 receptor, and TMPRSS2 can enable the virus to bind to the receptor more efficiently. Following viral infection, a range of responses occur. CCL2 released by the ENS recruits macrophages through the CCL2/CCR2 pathway. The recruitment of various inflammatory cells leads to the release of inflammatory factors. There are also changes in gut microbiota and the expression of sodium channel isoforms