Ebola Survivors Still A Transmission Threat

Courtesy Photo | Marburg virus particles (in blue) and sperm originating from the seminiferous tubule, a site of immune privilege and sperm production in the testes, of a non-human primate that survived Marburg virus infection. (USAMRIID)  

FORT BELVOIR, VIRGINIA, UNITED STATES

11.16.2018

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

The 2014 - 2016 Ebola epidemic in West Africa infected nearly 29.000 people, according to the World Health Organization. Of those infected, more than 11,000 died from the disease leaving more than 17,000 survivors. Disturbingly though, follow-up studies have detected Ebola RNA persisting in some of those survivors even 18 months after recovery. Despite the end of the epidemic, the viral threat still exists which can negatively impact deployed warfighter readiness. It has been determined that sexual transmission of the disease is a cause.

“Sexual transmission of Ebola virus has been implicated in the initiation of entirely new transmission chains,” Xiankun Zeng, Ph.D., explained after conducting a recent study. “Our study illustrates the mechanism behind testicular filovirus persistence and sexual transmission of filoviruses.”
Unfortunately, this is not unique to the virus, as other filoviruses, such as Marburg, have been shown to persist in the testes and other immune privileged areas according to a recent article in Cell Host and Microbe.
Due to this threat, the Defense Threat Reduction Agency’s Chemical and Biological Technologies Department partnered with the U.S. Army Medical Research Institute of Infectious Diseases to better understand the problem in order to increase protection for those in areas of at-risk populations.

Immune privileged areas are parts of the human body where antigens can exist without eliciting an immune response. Stopping the mechanisms of outbreak will also protect warfighters deployed to areas endemic to filoviruses.

Sexual transmission of filoviruses was first reported in 1968 after an outbreak of Marburg virus. Most recently, sexual transmission led to flare-ups of Ebola during the outbreak. How filoviruses establish testicular persistence and are shed in semen, however, was unknown.

Led by Zeng, investigators conducted a study using non-human primates to examine the persistence of Marburg virus in the testes of animals that survived infection.

The team found that Marburg virus persists in the seminiferous tubules, which are the sites of immune privilege and sperm production in the testes. Persistence leads to severe testicular damage, including cell depletion and breakdown of the blood-testis barrier. In addition, they identified a type of specialized cells, known as the Sertoli cells, as the reservoir for Marburg virus.

“Importantly, we also identified local infiltration of immunosuppressive regulatory T cells, which may play an important role in sustaining Marburg virus persistence,” said Zeng. “Targeting these T cells may help to clear Marburg virus from the testes, thereby preventing sexual transmission of the virus.”

About 30 percent of the non-human primates that survived the virus infection after antiviral treatment still had persistent infection in the testes, but not in other common target organs such as the liver, spleen and lymph nodes. The fact that it takes longer for Marburg virus to infect the testes strongly suggests that early intervention with therapeutics can prevent testicular persistence.

According to Zeng, the team’s next step is to develop animal models to evaluate the efficacy of medical countermeasures to prevent and clear Marburg and Ebola viral persistence in the testes.

With warfighters increasingly deploying to areas endemic to filoviruses, preventing local outbreaks will help keep them safe while limiting the risk of another epidemic.

DTRA CB POC: Maj. Jeffrey Froude, Ph.D.; [e-mail] USAMRIID POC: Xiankun (Kevin) Zeng, Ph.D.; [e-mail]

• Date Taken: 11.16.2018
• Date Posted: 11.16.2018 14:05
• Story ID: 300292
• Location: FORT BELVOIR, VIRGINIA, US