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Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors

Nature Microbiology volume 7, pages 1980–1986 (2022)Cite this article

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Abstract

Close contact through sexual activity has been associated with the spread of monkeypox virus (MPXV) in the ongoing, global 2022 epidemic. However, it remains unclear whether MPXV replicates in the testes or is transmitted via semen to produce an active infection. We carried out a retrospective analysis of MPXV-infected crab-eating macaque archival tissue samples from acute and convalescent phases of infection of clade I or clade II MPXV using immunostaining and RNA in situ hybridization. We detected MPXV in interstitial cells and seminiferous tubules of testes as well as epididymal lumina, which are the sites of sperm production and maturation. We also detected inflammation and necrosis during the acute phase of the disease by histological analysis. Finally, we found that MPXV was cleared from most organs during convalescence, including healed skin lesions, but could be detected for up to 37 d post-exposure in the testes of convalescent macaques. Our findings highlight the potential for sexual transmission of MPXV in humans.

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Fig. 1: Monkeypox virus infection in the testes of macaques with acute infection.
Fig. 2: A monkeypox virus-specific RNA in situ hybridization method.
Fig. 3: Monkeypox virus in the seminiferous tubules of testes and epididymal lumina.
Fig. 4: Persistence of Monkeypox virus in the testes of crab-eating macaque survivors.

Data availability

All animals and tissue staining information in the present study are listed in Supplementary Tables 1 and 2.

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Acknowledgements

We thank J. Writer (United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA) for critically editing the manuscript and J. Huggins (USAMRIID) for his contribution to the original animal studies. The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the US Department of the Army, the US Department of Defense, or of the institutions and companies affiliated with the authors. In no event shall any of these entities have any responsibility or liability for any use, misuse, inability to use, or reliance upon the information contained herein. The US departments do not endorse any products or commercial services mentioned in this publication.

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  1. Jennifer L. Chapman

    Present address: Labcorp Early Development Laboratories Inc., Chantilly, VA, USA

Authors and Affiliations

  1. United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA

    Jun Liu, Eric M. Mucker, Jennifer L. Chapman, April M. Babka, Jamal M. Gordon, Ashley V. Bryan, Jo Lynne W. Raymond, Todd M. Bell, Paul R. Facemire, Arthur J. Goff, Aysegul Nalca & Xiankun Zeng

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Contributions

X.Z. conceived and designed the experiments. J.L., A.M.B., J.M.G., A.V.B. and X.Z. performed all the staining and tissue analysis. E.M.M., A.J.G. and A.N. performed NHP studies or provided samples. J.L.C., J.L.W.R., T.M.B. and P.R.F. performed histopathological analysis. X.Z. interpreted the data and wrote the manuscript with input from all authors.

Corresponding author

Correspondence to Xiankun Zeng.

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Nature Microbiology thanks Hideki Hasegawa and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Characterization of inflammatory cells in the testicular tissue with MPXV persistence.

a,b, Low magnification immunofluorescence imaging demonstrates infiltration of CD68+ monocytes/macrophages (magenta in a), CD3+ T cells (green in a), myeloperoxidase (MPO)+ neutrophil granulocytes (green in b), and CD8+ T cells (magenta in b) in the areas surrounding the granulomas in the testes of MPXV survivors. Debris of MPO+ neutrophil granulocytes (green in b) are concentrated in the necrotic center of granulomas (regions circled by white dashed lines) in which MPXV persists. Representative immunofluorescence staining image shown from n = 2 survivors. Nuclei were counterstained blue with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar, 100 µm.

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Liu, J., Mucker, E.M., Chapman, J.L. et al. Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors. Nat Microbiol 7, 1980–1986 (2022). https://doi.org/10.1038/s41564-022-01259-w

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