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Microparticles mediate human papillomavirus type 6 or 11 infection of human macrophages

Cellular & Molecular Immunology volume 14, pages 395–397 (2017)Cite this article

Macrophage; Microparticles; HPV infection Although macrophages are very important in antiviral immune responses, various types of viruses such as the human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human cytomegalovirus, and poliovirus are capable of infecting macrophages. However, the underlying mechanisms remain incompletely understood. Recent studies highlight that cells during activation or apoptosis may shed components of the plasma membranes encapsulating cytoplasmic elements into the extracellular space. These released vesicles are known as microparticles (MPs) with 0.1–1 μm sizes.1 MPs can function as vectors to deliver information materials to other cells,2,3,4 implying a possibility of MP-mediated virus infection of macrophages. In fact, MPs are proposed to serve as a ‘Trojan horse’-like mechanism to transfer infectious particles such as the HIV virus to cells.5,6 Here, we provide evidence that human papillomavirus (HPV) may infect macrophages through the MP-mediated pathway.

Next, we wondered the pathway by which HPV entered into macrophages. Since HPV particles are ∼50 nm in diameter, the above genital wart-derived supernatants were filtered with 100 nm size filters to get rid of larger nonviral components. However, the filtered supernatants did not cause the HPV infection of macrophages (Figure 1e), suggesting HPV particles might not infect macrophages directly. Given that cell membrane-derived MPs with 100–1000 nm in size can transfer various materials between cells,2,3 we speculated that infection of keratinocytes by HPV resulted in the release of MPs that encapsulated viral particles, thereby mediating HPV infection of macrophages. To test this, we isolated MPs from the wart supernatants according to previous reports,7,8 and then incubated the MPs with macrophages for 6 hours and then refreshed the medium. Twenty-four hours later, macrophages were harvested for HPV E6 mRNA detection by RT-PCR. As expected, HPV mRNA was detected in the experiment group, but not in the control group in which MPs were isolated from healthy peripheral blood (Figure 1f). Meanwhile, the supernatants were used to isolate the second generation of MPs to further incubate with new macrophages. Again, the third and fourth generations of MPs were prepared for macrophage co-culture with the same protocol. Consistently, all those macrophages were found to express HPV mRNA (Figure 1f). Corroborating these findings, macrophages containing HPV were also confirmed by immunocytochemistry (Figure 1g), and HPV particles in macrophages were observed under an electron microscope (Figure 1h). More convincingly, additional five samples from five genital wart patients we tested. The repeated experiments all obtained the same results (Figure 1f). Taken together, these data suggested that the HPV may infect macrophages through the MP pathway, though how MPs mediated HPV infection of macrophages remains unanswered.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81472000), National Basic Research Program of China (2014CB542103), National Science Fund for Distinguished Young Scholars of China (81225021).

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Author notes

  1. Yuchun Cao and Chunlei Liu: Yuchun Cao and Chunlei Liu contributed equally to this work.

  2. Dr Bo Huang, State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. E-mail: tjhuangbo@hotmail.com

Authors and Affiliations

  1. Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

    Yuchun Cao, Chunlei Liu, Zhichao Gu, Yong Zhang & Yi Duan

  2. State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yi Zhang, Huafeng Zhang, Ke Tang & Bo Huang

  3. Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

    Bo Huang

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology’s website. (http://www.nature.com/cmi).

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Cao, Y., Liu, C., Gu, Z. et al. Microparticles mediate human papillomavirus type 6 or 11 infection of human macrophages. Cell Mol Immunol 14, 395–397 (2017). https://doi.org/10.1038/cmi.2015.30

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