Prevalence, Cell Tropism, and Clinical Impact of Human Parvovirus Persistence in Adenomatous, Cancerous, Inflamed, and Healthy Intestinal Mucosa

Abstract

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.

Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

“…[19][20][21] Similarly, human bocavirus 1 (HBoV1) DNA has been detected in tissues from individuals without acute viral infection, including tonsils, lung and intestinal mucosa. [22][23][24][25] However, reports on B19V and HBoV1 activity in the form of spliced mRNA or replication in tissues have furthermore been very scarce. 23,24 This makes CuV especially intriguing compared to its relatives.…”

Viral DNA in submandibular gland tissue with an inflammatory disorder

“…In this study, B19V was detected in 20% of the salivary gland samples and seemed to be more frequent in the IgG4-negative samples (26%) than in the IgG4-positive samples (15%), however, with no statistical significance. B19V mainly persists in B lymphocytes and endothelial cells but has only been reported to replicate in erythroid progenitor cells [ 23 , 26 , 48 ]. Therefore, although B19V DNA was detected in the analyzed salivary gland samples, the virus is most likely only present as transcriptionally inactive genomes inside the infected cells, as shown before in vascular endothelial cells and lymphoid B cells of the intestinal mucosa [ 48 ].…”

“…B19V mainly persists in B lymphocytes and endothelial cells but has only been reported to replicate in erythroid progenitor cells [ 23 , 26 , 48 ]. Therefore, although B19V DNA was detected in the analyzed salivary gland samples, the virus is most likely only present as transcriptionally inactive genomes inside the infected cells, as shown before in vascular endothelial cells and lymphoid B cells of the intestinal mucosa [ 48 ].…”

“…The gene transcript used for the HHV-6B probe is only expressed during the replication phase in the acute infection, and since HHV-6B persists latent in the salivary gland tissue, the staining signal might not have been strong enough to be visualized in RNAscope. However, the probes should be able to attach to the genomic DNA strand and thus be visible in RNAscope, even though mRNA is not present [ 31 , 48 ].…”

Human Bocavirus in Childhood: A True Respiratory Pathogen or a “Passenger” Virus? A Comprehensive Review

“…A recent study by Xu et al provides new insights into tonsillar HBoV1 persistence; the authors found HBoV1 persistence only in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In these cells, the virus uptake was significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis [ 54 ]. The HBoV immune response is schematized in Figure 1 .…”