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Emerg Microbes Infect. 2019;8(1):1108-1121. doi: 10.1080/22221751.2019.1637072.

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

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a The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine , Hershey , PA , USA.
b Department of Pathology, Pennsylvania State University College of Medicine , Hershey , PA , USA.
c Tumor Virus RNA Biology Section, RNA Biology Laboratory, National Cancer Institute, NIH , Frederick , MD , USA.
d Department of Immunology and Microbiology, School of Basic Medical Sciences, Wenzhou Medical University , Wenzhou , People's Republic of China.
e Department of Comparative Medicine, Pennsylvania State University College of Medicine , Hershey , PA , USA.
f Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, NIH , Frederick , MD , USA.
g CCR Collaborative Bioinformatics Resource (CCBR), Center for Cancer Research, NCI, NIH , Bethesda , MD , USA.
h Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research , Frederick , MD , USA.
i Department of Microbiology and Immunology, Pennsylvania State University College of Medicine , Hershey , PA , USA.


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.


CRPV/rabbit model; MmuPV1/mouse model; Papillomavirus; animal models; blood transfusion; viral infection

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