ABSTRACT
There is increasing evidence of gastrointestinal (GI) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. Publicly available and in-house single-cell RNA-sequencing datasets from the GI tract were queried. Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2. Therefore, the lower GI tract represents the most likely site of SARS-CoV-2 entry leading to GI infection.
Subject(s)
Betacoronavirus/metabolism , Enterocytes/metabolism , Lower Gastrointestinal Tract/metabolism , Peptidyl-Dipeptidase A/genetics , Serine Endopeptidases/genetics , Angiotensin-Converting Enzyme 2 , Base Sequence , COVID-19 , Cells, Cultured , Coronavirus Infections/pathology , Enterocytes/virology , Gastrointestinal Diseases/virology , Humans , Lower Gastrointestinal Tract/virology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , SARS-CoV-2 , Sequence Analysis , Serine Endopeptidases/metabolism , Virus InternalizationABSTRACT
The composition of gastrointestinal tract viromes has been associated with multiple diseases. Our understanding of virus communities in the GI tract is still very limited due to challenges in sampling from different GI sites. Here we defined the GI viromes of 15 rhesus macaques with chronic diarrhea. Luminal content samples from terminal ileum, proximal and distal colon were collected at necropsy while samples from the rectum were collected antemortem using a fecal loop. The composition of and ecological parameters associated with the terminal ileum virome were distinct from the colon and rectum samples; these differences were driven by bacteriophages rather than eukaryotic viruses. The six contigs that were most discriminative of the viromes were distantly related to bacteriophages from three different families. Our analysis provides support for using fecal loop sampling of the rectum as a proxy of the colonic virome in humans.
Subject(s)
Bacteriophages/physiology , Biodiversity , Diarrhea/veterinary , Lower Gastrointestinal Tract/virology , Macaca mulatta , Primate Diseases/virology , Animals , Bacteriophages/classification , Bacteriophages/genetics , Chronic Disease , Colon/pathology , Colon/virology , Contig Mapping , Diarrhea/virology , Feces/virology , Ileum/pathology , Ileum/virology , Lower Gastrointestinal Tract/pathology , Metagenome , Rectum/virologyABSTRACT
Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barré syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.
Subject(s)
Zika Virus Infection/immunology , Zika Virus Infection/virology , Animals , Cerebrospinal Fluid/virology , Inflammation/immunology , Lower Gastrointestinal Tract/virology , Lymph Nodes/virology , Macaca mulatta , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Many studies in the literature have shown that Epstein-Barr virus (EBV) is associated with several human lymphoid and epithelial malignancies. However, the prevalence of EBV in non-Hodgkin lymphoma (NHL) of the lower gastrointestinal (GI) tract has not been fully elucidated. AIM: The aim of this study was to determine the presence and distribution of EBV in formalin-fixed paraffin-embedded tissue samples obtained from 18 Malaysian patients diagnosed with NHL of the lower GI tract. METHODS: The GI tract lymphoma tissue samples analyzed for the presence of EBV were divided into the following groups: NHL of the small intestine (seven cases); NHL of the ileocecum (ten cases); and NHL of the rectum (one case). The presence of EBV-encoded RNA (EBER) in all of the above tissue samples was tested for using conventional in situ hybridization technology. RESULTS: Two of 18 cases (11.1%) of NHL of the lower GI tract demonstrated positive signals for EBV/EBER. In the first positive case, EBV/EBER signals were located in lymphoma cells in the serosa layer of the small intestine. In the second EBV/EBER-positive case, EBV/EBER signals were detected in diffuse B-cell lymphoma of the ileocecum. CONCLUSION: These findings demonstrate a rare association between EBV and lower GI tract lymphomas in this group of Malaysian patients.