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Protein fragments, called amyloid fibrils, in human sperm significantly increase Ebola virus infection and protect the virus from harsh environmental conditions such as heat and dehydration. Researchers at the Perelman School of Medicine at the University of Pennsylvania report these findings in a study published this week in the Proceedings of the National Academy of Sciences (PNAS).
Although the Ebola virus is transmitted primarily through direct contact with blood and other bodily fluids from infected people, follow-up studies from the 2014 outbreak have shown that men can harbor the virus in their body. sperm for at least 2.5 years. Meanwhile. The Penn team believes that targeting amyloids in sperm could prevent a sexually transmitted spread of Ebola.
"The sexual transmission of the Ebola virus poses a significant public health problem, particularly in light of the ongoing Ebola outbreak in the Democratic Republic of the Congo," said Paul Bates, Ph.D. a professor of microbiology.
Sexual transmission has also been linked to the resurgence of the Ebola virus in Guinea, which had previously been declared free of Ebola during the Ebola outbreak in West Africa. However, the role of host factors involved in sexual transmission has remained poorly understood. Anti-amyloid strategies, such as the creation of small molecules that disrupt its structure, have been developed to slow or halt HIV transmission. The researchers suggest that this approach could be tested for its ability to reduce infection in Ebola sexual transmission patterns.
Several types of amyloid found in sperm increase the transmission and infection of other viruses, such as HIV, by helping the virus to attach to the membrane surrounding the host cells. In a previous study, James Shorter, PhD, an associate professor of biochemistry and biophysics and co-author of the PNAS study, identified how yeast heat shock proteins and a small molecule called CLR01 could disrupt the formation of amyloid fibrils found in sperm to make human immune cells less likely to be infected with HIV. Stephen Bart, PhD, postdoctoral fellow at Bates Laboratory and first author of PNAS study, applied what he learned about the study of HIV to investigate the details of the sexual transmission of the Ebola virus.
To test the ability of amyloids to improve infection, benign viruses with the Ebola glycoprotein (a marker on the outside of the viral particle) were incubated with physiological concentrations of sperm amyloid before to infect various types of human cells including macrophages. Ebola virus in humans. The levels of infection of cells with this benign Ebola virus and amyloids were about 20 times higher than cells with the virus alone.
Co-authors Courtney Cohen and John M. Dye of the Division of Virology at the US Army Medical Research Institute found similar results using Ebola virus living in biosecurity level facilities 4 in Frederick, MD.
The team also found that amyloids improved the binding of the virus to cells and increased its ability to be internalized by host cells. Fibrils that worked in semen significantly altered the physical properties of the virus, making it more able to survive in high temperature, less humid internal body environments.
"Given the potential for sexual transmission to trigger new chains of Ebola infection, we believe we have found relevant factors that could be important targets to inhibit the spread of the Ebola virus," Bart said.
The next steps for the team are to determine if amyloids have an effect on Ebola in models of vaginal infection and if compounds that disrupt amyloids are protective. In addition, they plan to analyze amyloids found in other sites, such as the human intestine, to see if they play a role in other types of infections. viral infections.
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