Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS

Diagn Pathol. 2022 Jan 14;17(1):9. doi: 10.1186/s13000-022-01193-9.

Abstract

Background: Cytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases.

Methods: Using nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively.

Results: A total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p < 0.001), and cecum (p < 0.001), there were notably less positive epithelial cells than mesenchymal cells. The expression levels of PDGFRα and Nrp2 in the mesenchymal cells were higher than the epithelial cells in cardia, cecum, colon, sigmoid, and rectum, especially in the areas with ulcers. However, Nrp2 in the epithelial cells was higher than that in the duodenum. Moreover, the positive CMV DNA in peripheral blood was related to the CMV-positive cell count, as well as the ulceration in GI tract (p = 0.035 and 0.036, respectively).

Conclusions: The colon has been identified as the GI site with the highest susceptibility to CMV infection. There are different CMV-infected cells in the different sites of the GI that relate to the expression level of PDGFRα and Nrp2. CMV DNA positive in the blood is related to the positive CMV cell count, as well as ulceration in the GI tract.

Keywords: CMV; Cell tropism; Clinicopathological features; Digestive tract; HIV/AIDS; Nrp2; PDGFRα.

MeSH terms

  • AIDS-Related Opportunistic Infections / diagnosis*
  • AIDS-Related Opportunistic Infections / metabolism
  • AIDS-Related Opportunistic Infections / pathology
  • AIDS-Related Opportunistic Infections / virology
  • Adult
  • Biomarkers / metabolism
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Female
  • Gastrointestinal Diseases / diagnosis*
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / virology
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Gastrointestinal Tract / virology*
  • Humans
  • Male
  • Middle Aged
  • Viral Tropism*

Substances

  • Biomarkers