Study: Amyloid proteins in semen increase Ebola spread, protect virus

As Ebola developments in the Democratic Republic of the Congo (DRC) continue to suggest the outbreak may be contained, health officials will remain vigilant about the threat of sexual activity reigniting transmission in the weeks and months ahead, and a new study published yesterday hints at why the virus can linger in semen.

The DCR's health ministry today reported three new suspected cases from Bikoro and Iboko, as tests ruled out three earlier suspected cases, bringing the total to 56, including 38 confirmed, 15 probable, and 3 suspected. The number of deaths increased by 1 to 29. Today's numbers reflect a fatal probable case that was added to the total, based on investigation into an earlier community death in Iboko in a person who was a contact of one of the early cases.

The monitoring period ends tomorrow for the 161 contacts of the last confirmed case, a patient whose symptoms began on Jun 2.

At a media briefing in Geneva today, the World Health Organization (WHO) said though it was "cautiously confident" about the situation in the DRC, an aggressive response needs to continue, and health teams are following up on about 20 alerts per day.

"Experience has shown us that it only takes one case to set off a fast-moving outbreak," the WHO said in briefing notes.

Another piece of the sexual transmission puzzle

Sexual transmission of Ebola has been known to occur as long as 6 months after infection, and a study published in 2017 found evidence that Ebola RNA can linger in semen for more than 2 years after symptom onset. The transmission route was suspected in illness clusters that occurred toward the end of West Africa's outbreak.

In the new study, a research team focused on protein fragments in semen known as amyloid fibrils, which are already known to enhance transmission of other viruses, such as HIV, by helping the virus attach to the surfaces of surrounding host cells. Earlier findings on semen amyloids and HIV has already led developments aimed at disrupting amyloids, such as small molecules that can disrupt their structure, a tactic that could slow or halt HIV transmission.

In the journal Proceedings of the National Academies of Sciences (PNAS) yesterday, a research team based at the University of Pennsylvania School of Medicine described how they exposed benign viruses that contained the Ebola virus glycoprotein to physiologic concentrations of semen amyloids before infecting different human cell types, including macrophages, the Ebola virus' main target.

They found that infection levels with the amyloid-exposed viruses were 20 times higher than with the virus alone. Study coauthors from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) found similar results in experiments involving live Ebola in a biosafety level 4 lab in Frederick, Md.

Amyloids enhanced the binding of the virus to cells and increased virus ability to be internalized by host cells. Fibrils within semen significantly changed the physical properties of the virus, making it easier for them to survive in internal body environments of high temperature and less moisture, according to the study.

Stephen Bart, PhD, the study's first author and postdoctoral fellow at the University of Pennsylvania School of Medicine, said in a press release from the school, "Given the potential for sexual transmission to spark new Ebola infection chains, we feel we have found relevant factors that may be important targets for inhibiting the spread of Ebola."

For their next steps, the researchers will explore if amyloids have an impact on Ebola in vaginal infection and if compounds that disrupt amyloids can protect against Ebola. Also, scientists hope to look at amyloids in other body sites such as the gut to see if they play a role in other types of viral infection.

Urban spread lessons from Liberia

In another medical literature development, researchers from Liberia yesterday writing in a letter to The Lancet commented on the rural-to-urban spread of Ebola in the DRC's recent outbreak, a pattern that was first seen in West Africa's outbreak. "There has been an eerie mirroring of events," they wrote, noting that the urban spread of the disease in West Africa was a key factor in the epidemic's unprecedented case counts.

"Given the parallel scenario of cases emerging in Mbandaka, the response in upcoming weeks and its sensitivity to the local context will be critical in informing the final outbreak size in the DRC," the group wrote.

Understanding why Mbandaka's index case-patient decided to leave Bikoro for the province's capital city would yield important lessons, as it did in Liberia's urban areas. They said the patient could have been seeking care given inadequate facilities in the village, which would focus the investigation on exposures at hospitals and clinics—similar to what occurred in Monrovia's first case.

The experts also wrote that the patient might have fled to the city to get away from and seek relief for cultural threats, such as attributing illness to a supernatural cause such as a curse, a situation that sparked a second wave of transmission in Monrovia.

Based on lessons learned in the urban spread of Ebola, the three authors suggest five actions for delivering a trusted response for controlling Ebola transmission. They include providing sufficient point-of-need care in rural areas, implementing and spotlighting successful treatment interventions, debunking rumors and generating data, balancing public health with individual rights, and practicing safe burials.

"Understanding root causes of disease emergence in urban DRC will be essential to preventing additional rural to urban spread and to containing the outbreak within urban centers," they wrote.

See also:

Jun 25 PNAS abstract

Jun 26 DRC daily Ebola update

Jun 25 University of Pennsylvania Medical School press release

Jun 25 Lancet letter

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