Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

Nancy M Cladel,Pengfei Jiang,Jingwei J Li,Xuwen Peng,Timothy K Cooper,Vladimir Majerciak,Karla K Balogh,Thomas J Meyer,Sarah A Brendle,Lynn R Budgeon,Debra A Shearer,Regina Munden,Maggie Cam,Raghavan Vallur,Neil D Christensen,Zhi-Ming Zheng,Jiafen Hu

doi:10.1080/22221751.2019.1637072

Abstract

ABSTRACT Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

Highlights

This study grew out of an observation made in 2005 (Bodaghi et al, 2005a) that a subset of children with human immunodeficiency virus (HIV) had detectable levels of human papillomavirus (HPV) in their peripheral blood mononuclear cells (PBMCs)
Local papillomavirus infection: An infection initiated by the direct application of virus or viral
Stomach tissues are not known to be permissive for papillomavirus infection, the literature suggests that HPVs may be associated with a subset of gastric cancers. These results indicate that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection and subsequent cancers. 66 67 68 69 70

Summary

Introduction

This study grew out of an observation made in 2005 (Bodaghi et al, 2005a) that a subset of children with HIV had detectable levels of human papillomavirus (HPV) in their peripheral blood mononuclear cells (PBMCs). Some of these children were hemophiliacs who had contracted HIV through contaminated blood. HPV was detected in three out of the 19 seemingly healthy blood donors. A later study in 2009 demonstrated that HPV DNA is present in about 8.3% of healthy donor PBMCs in Australia (Chen et al, 2009). HPV has been detected in many malignant tissues, including the head and neck (Taberna et al, 2017), esophagus (Agalliu et al, 2018), lung (Shikova et al, 2017), colorectum (Bodaghi et al, 2005b) (Baandrup et al, 2014), prostate (Glenn et al, 2017; Tachezy et al, 2012), breast (ElAmrani et al, 2018; Malhone et al, 2018)

Results

Discussion

Conclusion