Scientists detect the monkeypox virus in the testes of macaque monkeys during an acute infection

Scientists detect the monkeypox virus in the testes of macaque monkeys during an acute infection

For the first time, scientists have detected the monkeypox virus in the testes of macaque monkeys during the acute phase of infection, according to a study published online today in the journal Nature Microbiology. In addition, the team found preliminary evidence of persistent infection in two animals that survived the challenge with the virus. Their findings highlight the potential for sexual transmission of the virus in humans.

The ongoing monkeypox outbreak in 2022 has been linked to sexual contact in patients with laboratory-confirmed infection. Because the virus can be transmitted through direct contact with body fluids and skin lesions, understanding the biology of monkeypox infection of the testes and virus shedding in semen has significant public health implications.

Researchers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) conducted a retrospective analysis of monkeypox virus infection in archived tissue samples from crab-eating macaques - a widely used non-human primate model to study the disease and evaluate the effectiveness of medical countermeasures such as monkeypox vaccines and treatments.

We examined tissue samples collected both during the acute phase of the disease, when the infection peaks, and during the recovery phase, when the infection gradually resolves. We detected monkeypox virus in interstitial cells and seminiferous tubules of the testes, as well as in the lumens of the epididymis, which are the sites of sperm production and maturation.”

Xiankun (Kevin) Zeng, Ph.D., senior author, USAMRIID

Importantly, Zeng said, the team also found preliminary evidence of persistent monkeypox virus infection in two convalescent crab-eating macaques that survived the challenge with the virus. Using histological analysis to microscopically analyze disease progression in tissue samples, the USAMRIID team discovered that while the monkeypox virus was cleared from most organs—and from healed skin lesions—during convalescence, it could be detected in the macaques' testes for up to 37 days after exposure.

USAMRIID investigators led by Zeng had previously shown that Ebola, Marburg, Nipah and Crimean-Congo hemorrhagic fever viruses can persist in certain organs of nonhuman primate survivors where the immune system is suppressed. These immune-privileged sites, which are similar in humans, include the eyes, brain and testes.

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While close contact through sexual activity has been linked to the spread of the monkeypox virus in the current global epidemic, it was unclear whether the virus replicated in the testes or was transmitted through semen.

"Our data demonstrate that monkeypox virus can be excreted into seminal fluid during both the acute and convalescent phases of the disease in crab-eating macaques," Zeng said. “It therefore seems plausible that transmission to humans could occur via semen in convalescent male patients.” The authors also noted that persistent viruses can be eliminated over time.

Because this was a retrospective study using archival tissue, virus isolation in semen was not possible, said Jun Liu, Ph.D., the paper's first author. Further studies are now needed to understand the origins, dynamics and effects of viral DNA secretion in semen and to confirm whether semen from convalescent monkeypox patients contains infectious viruses - particularly after healing of skin lesions.

In addition, according to the authors, the crabeater-macaque model may not fully reflect monkeypox in humans. The animals present with a more severe and fatal disease than that seen in humans, and the incubation period in the animals is shorter. In addition, this study used samples from animals exposed to virus isolates other than the currently circulating strain.

USAMRIID has decades of experience working with monkeypox and related highly dangerous pathogens. The Institute's many contributions to this field include a novel monkeypox respiratory model that closely approximates human exposure and clinical disease; the Phase 3 clinical trial supporting U.S. Food and Drug Administration approval of the JYNNEOS (Bavarian Nordic) vaccine for the prevention of smallpox and monkeypox in humans; and initial screening and preclinical efficacy testing of TPOXX (SIGA Technologies), the first drug approved for the treatment of smallpox. USAMRIID continues to develop monoclonal antibodies and other approaches to protect against orthopoxviruses.

Source:

US Army Medical Research Institute of Infectious Diseases

Reference:

Liu, J., et al. (2022) Retrospective detection of monkeypox virus in the testes of non-human primate survivors. Natural microbiology. doi.org/10.1038/s41564-022-01259-w.

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